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Irene Wapnir, MD

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Especialidades médicas y/o especialidades quirúrgicas

General Surgery

Trabajo y educación

Educación

Universidad Autonoma Metropolitana, Mexico, 05/01/1980

Primeros años de residencia

Lincoln Medical and Mental Health Center General Surgery Residency, Bronx, NY, 06/30/1981

Últimos años de residencia

Lincoln Medical and Mental Health Center General Surgery Residency, Bronx, NY, 06/30/1985

Subespecialidad

Rutgers Robert Wood Johnson Breast Surgery Fellowship, New Brunswick, NJ, 06/30/1988

Certificado(s) de especialidad

General Surgery, American Board of Surgery

Todo Publicaciones

Intratumoral plasmid IL-12 expands CD8+ T cells and induces a CXCR3 gene signature in triple-negative breast tumors that sensitizes patients to anti-PD-1 therapy. Clinical cancer research : an official journal of the American Association for Cancer Research Telli, M. L., Nagata, H., Wapnir, I. L., Acharya, C., Zablotsky, K. E., Fox, B. A., Bifulco, C. B., Jensen, S. M., Ballesteros-Merino, C., Le, M. H., Pierce, R. H., Browning, E., Hermiz, R., Svenson, L., Bannavong, D., Jaffe, K., Sell, J., Malloy Foerter, K., Canton, D. A., Twitty, C. G., Osada, T., Lyerly, H. K., Crosby, E. J. 2021

Abstract

PURPOSE: Triple-negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Antibodies targeting PD-1/PD-L1 have entered the therapeutic landscape in TNBC, but only a minority of patients benefit. A way to reliably enhance immunogenicity, T cell infiltration, and predict responsiveness is critically needed.EXPERIMENTAL DESIGN: Utilizing mouse models of TNBC, we evaluate immune activation and tumor targeting of intratumoral IL-12 plasmid followed by electroporation (tavokinogene telseplasmid; Tavo). We further present a single arm, prospective clinical trial of Tavo monotherapy in patients with treatment refractory, advanced TNBC (OMS-I140). Finally, we expand these findings using publicly available breast cancer and melanoma data sets.RESULTS: Single cell RNA sequencing of murine tumors identified a CXCR3 gene signature (CXCR3-GS) following Tavo treatment associated with enhanced antigen presentation, T cell infiltration and expansion, and PD-1/PD-L1 expression. Assessment of pre- and post-treatment tissue from patients confirms enrichment of this CXCR3-GS in tumors from patients that exhibited an enhancement of CD8+ T cell infiltration following treatment. One patient, previously unresponsive to anti-PD-L1 therapy, but who exhibited an increased CXCR3-GS after Tavo treatment, went on to receive additional anti-PD-1 therapy as their immediate next treatment after OMS-I140, and demonstrated a significant clinical response.CONCLUSIONS: These data show a safe, effective intratumoral therapy that can enhance antigen presentation and recruit CD8 T cells, which are required for the anti-tumor efficacy. We identify a Tavo treatment-related gene signature associated with improved outcomes and conversion of non-responsive tumors, potentially even beyond TNBC.

View details for DOI 10.1158/1078-0432.CCR-20-3944

View details for PubMedID 33593880

Intratumoral delivery of tavokinogene telseplasmid (plasmid IL-12) and electroporation induces an immune signature that predicts successful combination in patients Crosby, E. J., Nagata, H., Telli, M. L., Acharya, C. R., Wapnir, I., Zablotsky, K., Browning, E., Hermiz, R., Svenson, L., Bannavong, D., Malloy, K., Canton, D. A., Twitty, C. G., Osada, T., Lyerly, H. AMER ASSOC CANCER RESEARCH. 2021
Staged Approach to Autologous Reconstruction in the Ptotic Breast: A Comparative Study. Annals of plastic surgery Deptula, P. n., Yesantharao, P. n., Wapnir, I. n., Nguyen, D. n. 2021

Abstract

Nipple-sparing mastectomy (NSM) and autologous breast reconstruction are associated with higher patient satisfaction, quality of life, and aesthetic outcome. For patients with naturally ptotic breasts, this ideal reconstructive treatment of NSM and autologous breast reconstruction poses a challenge. We describe our experience in treating patients with ptotic natural breasts using a 2-staged approach: oncoplastic breast reduction in the first stage followed by nipple-sparing mastectomy and immediate autologous reconstruction in a second stage.We reviewed cases of patients with grade III ptosis who underwent a staged reconstruction approach with reduction mammaplasty followed by NSM and immediate reconstruction with an abdominally based free flap (2014-2019). We compared this group of patients to a second group who underwent staging with a technique of nipple-areola complex (NAC) devascularization. A survey was administered to assess for patient satisfaction and aesthetic outcome 1 year after the second stage procedure.Eight patients were identified in our reduction group, and 9 patients were identified in our devascularization group. No cases of total NAC necrosis were noted in either group (0%). Two cases of partial NAC necrosis were noted in the devascularization group (11%), whereas none were observed in the reduction group. All patients were satisfied with final outcome (100%, P = 1.0). Aesthetic scores across all factors were higher in the reduction group. Scores for overall outcome (4.6 vs 3.7, P = 0.04), natural appearance (4.8 vs 3.8, P = 0.01), breast contour (4.8 vs 3.2, P = 0.002), and position of breasts (5.0 vs 3.9, P = 0.03) were significantly higher in the reduction group.Breast ptosis no longer represents a contraindication for patients desiring nipple-sparing mastectomy and immediate autologous reconstruction. This series supports the use of a 2-staged approach with reduction mammaplasty in patients with naturally ptotic breasts. A staged reduction approach may offer fewer NAC complications while also allowing for superior aesthetic outcomes.

View details for DOI 10.1097/SAP.0000000000002725

View details for PubMedID 33470622

INTRATUMORAL PLASMID IL-12 EXPANDS CD8+T CELLS AND INDUCES A CLINICALLY VALIDATED CXCR3 SIGNATURE IN TRIPLE-NEGATIVE BREAST CANCER Crosby, E., Nagata, H., Telli, M., Acharya, C., Wapnir, I., Zablotsky, K., Browning, E., Hermiz, R., Svenson, L., Bannavong, D., Malloy, K., Canton, D., Twitty, C., Osada, T., Lyerly, H. BMJ PUBLISHING GROUP. 2020: A472
Immediate Targeted Nipple-Areolar Complex Re-Innervation: Improving Outcomes in Immediate Autologous Breast Reconstruction Tevlin, R., Wapnir, I., Nguyen, D. ELSEVIER SCIENCE INC. 2020: S226S227
Feasibility of Lumpectomy Surgery for Large Ductal Carcinoma In Situ Edquilang, J., Tsai, J., Park, Y., Wapnir, I. SPRINGER. 2020: S333
A randomized phase II study comparing surgical excision versus NeOadjuvant Radiotherapy followed by delayed surgical excision of Ductal carcinoma In Situ (NORDIS) Wapnir, I., DeMartini, W., Allison, K., Stone, K., Dirbas, F., Marquez, C., Ikeda, D., Pal, S., Tsai, J., Yang, R., West, R., McMillan, A., Telli, M., Horst, K. AMER ASSOC CANCER RESEARCH. 2020
Primary analysis of NRG-BR005, a phase II trial assessing accuracy of tumor bed biopsies in predicting pathologic complete response (pCR) in patients with clinical/radiological complete response after neoadjuvant chemotherapy (NCT) to explore the feasibility of breast-conserving treatment without surgery Basik, M., Cecchini, R. S., De Los Santos, J. F., Umphrey, H. R., Julian, T. B., Mamounas, E. P., White, J., Lucas, P. C., Balanoff, C., Tan, A. R., Weber, J. J., Edmonson, D. A., Brown-Glaberman, U. A., Diego, E. J., Teshome, M., Matsen, C. B., Seaward, S. A., Wapnir, I. L., Wagner, J. L., Tjoe, J. A., Thompson, A. M., Wolmark, N. AMER ASSOC CANCER RESEARCH. 2020
Phase 2, open-label study of intratumoral tavokinogene telseplasmid (tavo) plus electroporation in combination with intravenous pembrolizumab therapy in patients with inoperable locally advanced or metastatic triple-negative breast cancer (mTNBC) (KEYNOTE-890/OMS-I141) Telli, M. L., Wapnir, I., Devitt, B., Cuff, K., Soliman, H., Vinayak, S., Canton, D. A., Twitty, C., Foerter, K., Joshi, R. AMER ASSOC CANCER RESEARCH. 2020
Results from the expansion into multiple institutions for training in the use of the LUM imaging system for intraoperative detection of residual cancer in the tumor bed of female subjects with breast cancer clinical trial Ferrer, J., Carr, D., Blumencranz, P., Dodge, D., Dekhne, N., Wapnir, I., Hunt, K., Gold, L., Valente, S., Beitsch, P., Dyess, D., Hwang, S., Clark, L., Lesnikoski, B., Chagpar, A., Karp, S., Schlossberg, B., Madden, S., Chang, M., Smith, K., Strasfeld, D., Lee, W., Smith, B. AMER ASSOC CANCER RESEARCH. 2020
Expansion into multiple institutions for training in the use of the LUM Imaging System for intraoperative detection of residual cancer in the tumor bed of female subjects with breast cancer Smith, K., Ferrer, J., Carr, D., Blumencranz, P., Dodge, D., Dekhne, N., Wapnir, I., Hunt, K., Gold, L., Valente, S., Beitsch, P., Dyess, D., Hwang, S., Clark, L., Lesnikoski, B., Chagpar, A., Karp, S., Schlossberg, B., Gjylameti, L., Smith, B. AMER ASSOC CANCER RESEARCH. 2020
Adjuvant trastuzumab emtansine (T-DM1) vs trastuzumab (H) in patients with residual invasive disease after neoadjuvant therapy for HER2-positive breast cancer: KATHERINE subgroup analysis Mano, M. S., Loibl, S., Mamounas, E. P., von Minckwitz, G., Huang, C., Untch, M., Wolmark, N., Wapnir, I. L., Yang, Y., Conlin, A. K., Kuemmel, S., Saghatchian, M., DiGiovanna, M. P., Strunk, C., Zimovjanova, M., Song, C., Liu, H., Tesarowski, D., Blotner, S., Lam, L. H., Smitt, M., Geyer, C. E. AMER ASSOC CANCER RESEARCH. 2020
Autologous tumor cell vaccine induces antitumor T cell immune responses in patients with mantle cell lymphoma: A phase I/II trial. The Journal of experimental medicine Frank, M. J., Khodadoust, M. S., Czerwinski, D. K., Haabeth, O. A., Chu, M. P., Miklos, D. B., Advani, R. H., Alizadeh, A. A., Gupta, N. K., Maeda, L. S., Reddy, S. A., Laport, G. G., Meyer, E. H., Negrin, R. S., Rezvani, A. R., Weng, W. K., Sheehan, K. n., Faham, M. n., Okada, A. n., Moore, A. H., Phillips, D. L., Wapnir, I. L., Brody, J. D., Levy, R. n. 2020; 217 (9)

Abstract

Here, we report on the results of a phase I/II trial (NCT00490529) for patients with mantle cell lymphoma who, having achieved remission after immunochemotherapy, were vaccinated with irradiated, CpG-activated tumor cells. Subsequently, vaccine-primed lymphocytes were collected and reinfused after a standard autologous stem cell transplantation (ASCT). The primary endpoint was detection of minimal residual disease (MRD) within 1 yr after ASCT at the previously validated threshold of 1 malignant cell per 10,000 leukocyte equivalents. Of 45 evaluable patients, 40 (89%) were found to be MRD negative, and the MRD-positive patients experienced early subsequent relapse. The vaccination induced antitumor CD8 T cell immune responses in 40% of patients, and these were associated with favorable clinical outcomes. Patients with high tumor PD-L1 expression after in vitro exposure to CpG had inferior outcomes. Vaccination with CpG-stimulated autologous tumor cells followed by the adoptive transfer of vaccine-primed lymphocytes after ASCT is feasible and safe.

View details for DOI 10.1084/jem.20191712

View details for PubMedID 32558897

Immediate Targeted Nipple-Areolar Complex Reinnervation: Improving Outcomes in Gender-affirming Mastectomy. Plastic and reconstructive surgery. Global open Rochlin, D. H., Brazio, P. n., Wapnir, I. n., Nguyen, D. n. 2020; 8 (3): e2719

Abstract

Female-to-male mastectomy often renders the chest skin and nipple-areolar complex (NAC) insensate. We propose a new technique of preserving the intercostal nerves and using them to reinnervate the NAC after mastectomy.We performed a prospective analysis of transmasculine patients who underwent female-to-male mastectomy. The technique involves dissecting out the lateral intercostal nerves to length and performing a neurorrhaphy to nerve stumps at the base of the NAC. Sensory outcomes, as assessed with Semmes-Weinstein monofilaments, were compared to a cohort of patients who underwent mastectomy without neurotization.Ten patients with a mean age of 17.5 years (range: 16-19 years) underwent mastectomy. The final follow-up was a mean of 15.4 4.3 months for the treated group and 40.7 12.9 months for the control group. Compared to control patients, treated patients had significant improvement in sensation at the nipple (P 0.0002), areola (P = 0.0001), and peripheral breast skin (P = 0.0001). For treated patients, there was no statistically significant difference in sensation between preoperative and postoperative sensation in all tested areas at final follow-up.This proof of concept study suggests that immediate reinnervation of the NAC after mastectomy enhances recovery of NAC sensation in patients undergoing female-to-male mastectomy and may be further generalized to women undergoing postmastectomy breast reconstruction.

View details for DOI 10.1097/GOX.0000000000002719

View details for PubMedID 32537367

View details for PubMedCentralID PMC7253256

The Impact of Device Innovation on Clinical Outcomes in Expander-based Breast Reconstruction PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN Momeni, A., Li, A. Y., Tsai, J., Wan, D., Karin, M. R., Wapnir, I. L. 2019; 7 (12)
Use of Preoperative Radiation Therapy in Early-stage and Locally Advanced Breast Cancer CUREUS Koenig, J. L., Kozak, M. M., Sabolch, A., Horst, K., Tsai, J., Wapnir, I. L., Pollom, E. 2019; 11 (9)
Pretreatment Tattoo Marking of Suspicious Axillary Lymph Nodes: Reliability and Correlation with Sentinel Lymph Node ANNALS OF SURGICAL ONCOLOGY Patel, R., MacKerricher, W., Tsai, J., Choy, N., Lipson, J., Ikeda, D., Pal, S., De Martini, W., Allison, K. H., Wapnir, I. L. 2019; 26 (8): 245258
Expansion into multiple institutions for training in the use of the LUM Imaging System for intraoperative detection of residual cancer in the tumor bed of female subjects with breast cancer Smith, K., Ferrer, J. M., Smith, B. L., Hwang, E., Hunt, K. K., Dodge, D. G., Karp, S. E., Valente, S. A., Wapnir, I. L., Clark, L. P., Carr, D. R., Beitsch, P. D., Dyess, D. L., Lesnikoski, B., Blumencranz, P. W., Dekhne, N. S., Gold, L. P., Chagpar, A., Kacena, K., Gjylameti, L., Geissler, F. AMER ASSOC CANCER RESEARCH. 2019
KATHERINE: Trastuzumab emtansine vs trastuzumab as adjuvant therapy in patients with HER2-positive early breast cancer Mamounas, E. P., Geyer, C. E., Huang, C., Mano, M. S., Loibl, S., Untch, M., Wolmark, N., Rastogi, P., Schneeweiss, A., Redondo, A., Fischer, H. H., Jacot, W., Conlin, A. K., Arce-Salinas, C., Wapnir, I. L., Jackisch, C., DiGiovanna, M. P., Fasching, P. A., Crown, J. P., Wuelfing, P., Shao, Z., Caremoli, E., Wu, H., Lam, L. H., Tesarowski, D., Smitt, M., Douthwaite, H., Singel, S. M., von Minckwitz, G. E M H SWISS MEDICAL PUBLISHERS LTD. 2019: 13S
Pretreatment Tattoo Marking of Suspicious Axillary Lymph Nodes: Reliability and Correlation with Sentinel Lymph Node. Annals of surgical oncology Patel, R., MacKerricher, W., Tsai, J., Choy, N., Lipson, J., Ikeda, D., Pal, S., De Martini, W., Allison, K. H., Wapnir, I. L. 2019

Abstract

BACKGROUND: Tattooing is an alternative method for marking biopsied axillary lymph nodes (ALNs) before initiation of treatments for newly diagnosed breast cancer. Detection of black ink-stained nodes is performed under direct visualization at surgery and is combined with sentinel node (SLN) mapping procedures.METHODS: Women with newly diagnosed breast cancer who underwent fine or core-needle biopsy of suspicious ALNs were recruited. The nodal cortex and perinodal soft tissue was injected with 0.1-1.0ml of Spot (GI Supply) black ink under ultrasound guidance. Intraoperatively, black stained nodes were removed along with SLNs, noting concordance between the two.RESULTS: Sixty-six evaluable patients were enrolled (2013-2017). Nineteen received surgery first (Group 1) and 47 neoadjuvant therapy (NAT, Group 2). The average number of nodes tattooed was 1.16 for Group 1 and 1.04 for Group 2. The average interval from tattoo to surgery was 21days (range 1-62) for Group 1 and 148days (range 71-257) for Group 2. The tattooed node(s) were visually identified at surgery and corresponded to the sentinel lymph node(s) in 98.5% of cases (18/19 in Group 1 and 47/47 in Group 2). Of the 14 patients in Group 2 whose nodes remained positive following NAT, the tattooed node was the SLN associated with carcinoma.CONCLUSIONS: Tattooing is an alternative method for marking biopsied ALNs. Tattooed nodes coincided with SLNs in 98.5% of cases. This technique is advantageous, because it allows for fewer procedures and lower costs compared with other methods.

View details for PubMedID 31087176

Benefits of an interview match for breast fellowship positions Wapnir, I., Lo, I., Roth, A., Ashlagi, I., Melcher, M. SPRINGER. 2019: 27980
Clinical and pathological features of breast cancer among men and women with ATM and CDH1 mutations Tsang, A., Kingham, K., Kurian, A., Ford, J., Wapnir, I. SPRINGER. 2019: 6970
Preliminary results of a multi-center feasibility trial for real-time, intraoperative detection of residual breast cancer in lumpectomy cavity margins using the LUM Imaging System Smith, B., Kelly, B., Hunt, K., Hwang, S., Wapnir, I., Gadd, M., Specht, M., Hughes, K., Lanahan, C., Brown, C., Strasfeld, D., Kacena, K. SPRINGER. 2019: 43
Reducing the Burden of Fellowship Interviews Reply JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Melcher, M. L., Ashlagi, I., Wapnir, I. 2019; 321 (11): 1107
Reducing the Burden of Fellowship Interviews-Reply. JAMA Melcher, M. L., Ashlagi, I., Wapnir, I. 2019; 321 (11): 1107

View details for PubMedID 30874752

Mucocele-Like Lesions of the Breast on Core Needle Biopsy: an Institutional review and Meta-Analysis of the Literature Ylagan, L., Allison, K., Ikeda, D., Wapnir, I. NATURE PUBLISHING GROUP. 2019
Mucocele-Like Lesions of the Breast on Core Needle Biopsy: an Institutional review and Meta-Analysis of the Literature Ylagan, L., Allison, K., Ikeda, D., Wapnir, I. NATURE PUBLISHING GROUP. 2019
Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer NEW ENGLAND JOURNAL OF MEDICINE von Minckwitz, G., Huang, C., Mano, M. S., Loibl, S., Mamounas, E. P., Untch, M., Wolmark, N., Rastogi, P., Schneeweiss, A., Redondo, A., Fischer, H. H., Jacot, W., Conlin, A. K., Arce-Salinas, C., Wapnir, I. L., Jackisch, C., DiGiovanna, M. P., Fasching, P. A., Crown, J. P., Wuelfing, P., Shao, Z., Caremoli, E., Wu, H., Lam, L. H., Tesarowski, D., Smitt, M., Douthwaite, H., Singel, S. M., Geyer, C. E., KATHERINE Investigators 2019; 380 (7): 61728
Intratumoral tavokinogene telseplasmid and electroporation in pre-treated inoperable locally advanced or recurrent triple-negative breast cancer Telli, M. L., Zablotsky, K., Le, M. H., Canton, D., Browning, E., Bannavong, D., Gargosky, S., Wapnir, I. AMER ASSOC CANCER RESEARCH. 2019
Phase III study of trastuzumab emtansine (T-DM1) vs trastuzumab as adjuvant therapy in patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy including trastuzumab: Primary results from KATHERINE Geyer, C. E., Huang, C., Mano, M. S., Loibl, S., Mamounas, E. P., Untch, M., Wolmark, N., Rastogi, P., Fischer, H. H., Redondo, A., Jackisch, C., Jacot, W., Conlin, A. K., Schneeweiss, A., Wapnir, I. L., Fasching, P. A., DiGiovanna, M. P., Wuelfing, P., Arce-Salinas, C., Crown, J. P., Shao, Z., Caremoli, E., Wu, H., Lam, L. H., Tesarowski, D., Smitt, M., Douthwaite, H., Singel, S. M., von Minckwitz, G. AMER ASSOC CANCER RESEARCH. 2019
A phase 2 study of intratumoral tavokinogene telseplasmid (tavo) plus electroporation with pembrolizumab in patients with inoperable locally advanced or metastatic triple negative breast cancer Telli, M. L., Wapnir, I., Vinayak, S., Chang, J., Alemany, C., Twitty, C., Gargosky, S. AMER ASSOC CANCER RESEARCH. 2019
Dilemma in management of hemorrhagic myositis in dermatomyositis. Rheumatology international Chandler, J. M., Kim, Y. J., Bauer, J. L., Wapnir, I. L. 2019

Abstract

Dermatomyositis (DM) is a rare inflammatory disorder affecting the muscle and skin. DM patients can present with spontaneous muscle hemorrhage, a potentially fatal complication. The best practice for management of hemorrhagic myositis in these patients remains unclear. Here we discuss the case of a patient who presented with progressive muscle weakness and intermittent rash that was diagnosed with dermatomyositis. During admission, she developed spontaneous hemorrhagic myositis of the right pectoralis major treated with surgical evacuation. She also developed a spontaneous left anterior thigh hematoma which was treated conservatively. She recovered and showed no evidence of recurrent bleeding at either location. We performed a literature review and identified ten cases of spontaneous hemorrhage in DM patients, with a 60% mortality rate among reported cases. Given the high mortality rate associated with spontaneous hemorrhage in DM patients, it is important for physicians to be aware of the diagnosis, workup, and management strategies.

View details for DOI 10.1007/s00296-019-04501-7

View details for PubMedID 31872270

The Impact of Device Innovation on Clinical Outcomes in Expander-based Breast Reconstruction. Plastic and reconstructive surgery. Global open Momeni, A. n., Li, A. Y., Tsai, J. n., Wan, D. n., Karin, M. R., Wapnir, I. L. 2019; 7 (12): e2524

Abstract

Staged expander-based breast reconstruction represents the most common reconstructive modality in the United States. The introduction of a novel tissue expander with an integrated drain (Sientra AlloX2) holds promise to further improve clinical outcomes.Patients who underwent immediate expander-based pre-pectoral breast reconstruction were identified. Two cohorts were created, that is, patients who underwent placement of a conventional tissue expander [133MX (Allergan)] (Group 1) versus AlloX2 (Sientra) (Group 2). The study endpoint was successful completion of expansion with the objective being to investigate differences in outcome following expander placement.Fifty-eight patients underwent 99 breast reconstructions [Group 1: N = 24 (40 breasts) versus Group 2: N = 34 (59 breast)]. No differences were noted for age (P = 0.586), BMI (P = 0.109), history of radiation (P = 0.377), adjuvant radiotherapy (P = 1.00), and overall complication rate (P = 0.141). A significantly longer time to drain removal was noted in Group 1 (P < 0.001). All patients with postoperative infection in Group 1 required surgical treatment versus successful washout of the peri-prosthetic space via the AlloX2 drain port in 3 of 5 patients in Group 2 (P = 0.196). Furthermore, both cases of seroma in Group 1 required image-guided drainage versus in-office drainage via the AlloX2 drain port in 1 patient in Group 2 (P =0.333).The unique feature of the AlloX2 provides surgeons easy access to the peri-prosthetic space without altering any of the other characteristics of a tissue expander. This resulted in a reduced time to drain removal and facilitated management of postoperative seroma and infection.

View details for DOI 10.1097/GOX.0000000000002524

View details for PubMedID 32537287

View details for PubMedCentralID PMC7288893

Use of Preoperative Radiation Therapy in Early-stage and Locally Advanced Breast Cancer. Cureus Koenig, J. L., Kozak, M. M., Sabolch, A. n., Horst, K. n., Tsai, J. n., Wapnir, I. L., Pollom, E. n. 2019; 11 (9): e5748

Abstract

Purpose There is growing interest in delivering radiation preoperatively (preopRT) rather than postoperatively (postopRT) for breast cancer. Using the National Cancer Database, we evaluated the use and outcomes of preopRT in breast cancer. Methods We identified adult females diagnosed with non-metastatic breast cancer treated with definitive surgery and radiation between 2004 and 2014. Logistic regression models evaluated factors associated with use of preopRT in early-stage (clinical T1-3/N0-1) and locally advanced (clinical T4/N2-3) disease. Rates of breast-conserving surgery, breast reconstruction, positive surgical margins, and 30-day surgical readmissions were compared between patients receiving preopRT and postopRT. Results Of 373,595 patients who met our inclusion criteria, 1,245 (0.3%) patients received preopRT. Patients receiving preopRT were more likely to be of lower socioeconomic status and have tumors with higher T stage. Younger age and N1 (vs N0) disease predicted for use of preopRT in early-stage disease, while older age and N0 disease predicted for use of preopRT in the locally advanced setting. PreopRT patients were less likely to undergo breast-conserving surgery and more likely to have positive surgical margins. Rates of unplanned readmissions within 30 days of surgery were similar among patients treated with preopRT and postopRT. Conclusions PreopRT is a new treatment strategy for patients with breast cancer with different clinical and sociodemographic drivers of its use in the early-stage and locally advanced settings. We await the results of clinical trials studying the efficacy of this approach.

View details for DOI 10.7759/cureus.5748

View details for PubMedID 31723509

View details for PubMedCentralID PMC6825433

May the Interview Be With You: Signal Your Preferences. Journal of graduate medical education Melcher, M. L., Wapnir, I. n., Ashlagi, I. n. 2019; 11 (1): 3940

View details for DOI 10.4300/JGME-D-19-00002.1

View details for PubMedID 30805095

View details for PubMedCentralID PMC6375331

Methotrexate in the Treatment of Idiopathic Granulomatous Mastitis. The Journal of rheumatology Postolova, A. n., Troxell, M. L., Wapnir, I. L., Genovese, M. C. 2019

Abstract

Idiopathic granulomatous mastitis (IGM) is a disfiguring inflammatory breast disease without effective treatment. We report the largest IGM cohort treated with methotrexate monotherapy.Chart review was performed on patients evaluated by the Rheumatology Clinic, with histopathologically-established IGM, treated with methotrexate, and at least one follow up appointment.Nineteen female patients with an mean age of 33.5 years were identified. Most failed treatment with antibiotics, prednisone, and surgical intervention. By 15 months of treatment with methotrexate, 94% had disease improvement and 75% achieved disease remission.Methotrexate monotherapy is an effective treatment for IGM.

View details for DOI 10.3899/jrheum.181205

View details for PubMedID 31203215

Current Strategies for the Management of Locoregional Breast Cancer Recurrence ONCOLOGY-NEW YORK Wapnir, I. L., Khan, A. 2019; 33 (1): 1925
Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. The New England journal of medicine von Minckwitz, G., Huang, C., Mano, M. S., Loibl, S., Mamounas, E. P., Untch, M., Wolmark, N., Rastogi, P., Schneeweiss, A., Redondo, A., Fischer, H. H., Jacot, W., Conlin, A. K., Arce-Salinas, C., Wapnir, I. L., Jackisch, C., DiGiovanna, M. P., Fasching, P. A., Crown, J. P., Wulfing, P., Shao, Z., Rota Caremoli, E., Wu, H., Lam, L. H., Tesarowski, D., Smitt, M., Douthwaite, H., Singel, S. M., Geyer, C. E., KATHERINE Investigators 2018

Abstract

BACKGROUND: Patients who have residual invasive breast cancer after receiving neoadjuvant chemotherapy plus human epidermal growth factor receptor 2 (HER2)-targeted therapy have a worse prognosis than those who have no residual cancer. Trastuzumab emtansine (T-DM1), an antibody-drug conjugate of trastuzumab and the cytotoxic agent emtansine (DM1), a maytansine derivative and microtubule inhibitor, provides benefit in patients with metastatic breast cancer that was previously treated with chemotherapy plus HER2-targeted therapy.METHODS: We conducted a phase 3, open-label trial involving patients with HER2-positive early breast cancer who were found to have residual invasive disease in the breast or axilla at surgery after receiving neoadjuvant therapy containing a taxane (with or without anthracycline) and trastuzumab. Patients were randomly assigned to receive adjuvant T-DM1 or trastuzumab for 14 cycles. The primary end point was invasive disease-free survival (defined as freedom from ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause).RESULTS: At the interim analysis, among 1486 randomly assigned patients (743 in the T-DM1 group and 743 in the trastuzumab group), invasive disease or death had occurred in 91 patients in the T-DM1 group (12.2%) and 165 patients in the trastuzumab group (22.2%). The estimated percentage of patients who were free of invasive disease at 3 years was 88.3% in the T-DM1 group and 77.0% in the trastuzumab group. Invasive disease-free survival was significantly higher in the T-DM1 group than in the trastuzumab group (hazard ratio for invasive disease or death, 0.50; 95% confidence interval, 0.39 to 0.64; P<0.001). Distant recurrence as the first invasive-disease event occurred in 10.5% of patients in the T-DM1 group and 15.9% of those in the trastuzumab group. The safety data were consistent with the known safety profile of T-DM1, with more adverse events associated with T-DM1 than with trastuzumab alone.CONCLUSIONS: Among patients with HER2-positive early breast cancer who had residual invasive disease after completion of neoadjuvant therapy, the risk of recurrence of invasive breast cancer or death was 50% lower with adjuvant T-DM1 than with trastuzumab alone. (Funded by F. Hoffmann-La Roche/Genentech; KATHERINE ClinicalTrials.gov number, NCT01772472 .).

View details for PubMedID 30516102

Use of Preoperative Radiation Therapy in Early and Advanced Stage Breast Cancer Koenig, J. L., Kozak, M., Sabolch, A., Wapnir, I. L., Horst, K. C., Tsai, C. J., Pollom, E. ELSEVIER SCIENCE INC. 2018: E589
Matching for Fellowship Interviews JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Melcher, M. L., Ashlagi, I., Wapnir, I. 2018; 320 (16): 163940
Expansion into multiple institutions for training in the use of the LUM Imaging System for intraoperative detection of residual cancer in the tumor bed of female subjects with breast cancer Ferrer, J. M., Hwang, S., Hunt, K., Dodge, D., Chagpar, A., Grobmyer, S., Karp, S., Valente, S., Wapnir, I., Smith, K., Ramirez, E., Bischof, T., Strasfeld, D., Lee, D., Smith, B. AMER ASSOC CANCER RESEARCH. 2018
Intratumoral plasmid IL-12 and electroporation in pre-treated inoperable locally advanced or recurrent triple-negative breast cancer (TNBC) Telli, M. L., Zablotsky, K., Gargosky, S. E., Twitty, C. G., Wapnir, I. L. AMER ASSOC CANCER RESEARCH. 2018
Pathological confirmation of pre-chemotherapy biopsied and tattooed axillary lymph nodes Patel, R., MacKerricher, W., Tsai, J., Wood, L., Allison, K., Wapnir, I. SPRINGER. 2018: 42627
Efficacy of Chemotherapy for ER-Negative and ER-Positive Isolated Locoregional Recurrence of Breast Cancer: Final Analysis of the CALOR Trial JOURNAL OF CLINICAL ONCOLOGY Wapnir, I. L., Price, K. N., Anderson, S. J., Robidoux, A., Martin, M., Nortier, J. R., Paterson, A. G., Rimawi, M. F., Lang, I., Manuel Baena-Canada, J., Thurlimann, B., Mamounas, E. P., Geyer, C. E., Gelber, S., Coates, A. S., Gelber, R. D., Rastogi, P., Regan, M. M., Wolmark, N., Aebi, S., NRG Oncology, GEICAM Spanish Breast Canc Grp, BOOG Dutch Breast Canc Trialists G, Breast Int Grp 2018; 36 (11): 1073-+

Abstract

Purpose Isolated locoregional recurrence (ILRR) predicts a high risk of developing breast cancer distant metastases and death. The Chemotherapy as Adjuvant for LOcally Recurrent breast cancer (CALOR) trial investigated the effectiveness of chemotherapy (CT) after local therapy for ILRR. A report at 5 years of median follow-up showed significant benefit of CT for estrogen receptor (ER)-negative ILRR, but additional follow-up was required in ER-positive ILRR. Patients and Methods CALOR was an open-label, randomized trial for patients with completely excised ILRR after unilateral breast cancer. Eligible patients were randomly assigned to receive CT or no CT and stratified by prior CT, hormone receptor status, and location of ILRR. Patients with hormone receptor-positive ILRR received adjuvant endocrine therapy. Radiation therapy was mandated for patients with microscopically involved margins, and anti-human epidermal growth factor receptor 2 therapy was optional. End points were disease-free survival (DFS), overall survival, and breast cancer-free interval. Results From August 2003 to January 2010, 162 patients were enrolled: 58 with ER-negative and 104 with ER-positive ILRR. At 9 years of median follow-up, 27 DFS events were observed in the ER-negative group and 40 in the ER-positive group. The hazard ratios (HR) of a DFS event were 0.29 (95% CI, 0.13 to 0.67; 10-year DFS, 70% v 34%, CT v no CT, respectively) in patients with ER-negative ILRR and 1.07 (95% CI, 0.57 to 2.00; 10-year DFS, 50% v 59%, respectively) in patients with ER-positive ILRR ( Pinteraction = .013). HRs were 0.29 (95% CI, 0.13 to 0.67) and 0.94 (95% CI, 0.47 to 1.85), respectively, for breast cancer-free interval ( Pinteraction = .034) and 0.48 (95% CI, 0.19 to 1.20) and 0.70 (95% CI, 0.32 to 1.55), respectively, for overall survival ( Pinteraction = .53). Results for the three end points were consistent in multivariable analyses adjusting for location of ILRR, prior CT, and interval from primary surgery. Conclusion The final analysis of CALOR confirms that CT benefits patients with resected ER-negative ILRR and does not support the use of CT for ER-positive ILRR.

View details for PubMedID 29443653

View details for PubMedCentralID PMC5891132

Will oncotype DX DCIS testing guide therapy? A single-institution correlation of oncotype DX DCIS results with histopathologic findings and clinical management decisions MODERN PATHOLOGY Lin, C., Mooney, K., Choy, W., Yang, S., Barry-Holson, K., Horst, K., Wapnir, I., Allison, K. 2018; 31 (4): 56268
Axillary reverse mapping with indocyanine green or isosulfan blue demonstrate similar crossover rates to radiotracer identified sentinel nodes JOURNAL OF SURGICAL ONCOLOGY Foster, D., Choy, N., Porter, C., Ahmed, S., Wapnir, I. 2018; 117 (3): 33640

Abstract

Sentinel lymph node (SLN) resection is imperative for breast cancer staging. Axillary reverse mapping (ARM) can preserve arm draining nodes and lymphatics during surgery. ARM is generally performed with isosulfan blue (ISB), restricting its use for concurrent SLN biopsy. Indocyanine green (ICG) could serve as an alternative to ISB for ARM procedures.SLN mapping and biopsy was performed via periareolar injection of 99 technetium-sulfur colloid (99m TcSc, TSC). ISB and ICG were injected in the upper arm. Blue-stained lymphatics or nodes were visualized in the axilla; ICG was identified using the SPY Elite system.Twenty-three patients underwent SLN biopsy with or without axillary node dissection and ARM procedures. Twenty of these patients had at least one hot node; 12 patients had SLNs that were only hot, 6 hot/blue/fluorescent, and 2 hot/fluorescent. Overall, crossover of ARM agents with SLNs occurred in 8 cases. Inspection of the axillary cavity after SLN biopsy revealed fluorescent lymphatics and nodes remaining in 14 and 7 patients, respectively. Blue lymphatics and blue nodes were detected in fewer cases.Nearly one-third of patients showed crossover between breast and arm draining nodes, which provides insight as to why some patients develop lymphedema symptoms after SLN biopsy. ICG and ISB identify similar numbers of SLNs. As such ICG could substitute for ISB in ARM procedures.

View details for PubMedID 29228459

The Role of Tattooing Biopsied Axillary Lymph Nodes in Patients Undergoing Neoadjuvant Therapy Patel, R., Choy, N., Tsai, J., Pal, S., Lipson, J., Wapnir, I. SPRINGER. 2018: S94
Bridging gaps in breast cancer care: A pilot forum for mental health professionals Yang, R., Rabinowitz, B., Frank, M., Schapira, L., Wapnir, I. AMER ASSOC CANCER RESEARCH. 2018
Matching for Fellowship Interviews. JAMA Melcher, M. L., Ashlagi, I. n., Wapnir, I. n. 2018; 320 (16): 163940

View details for PubMedID 30422279

Hispanic Breast Cancer Patients Travel Further for Equitable Surgical Care at a Comprehensive Cancer Center HEALTH EQUITY Yang, R. L., Wapnir, I. 2018; 2 (1): 10916
Hispanic Breast Cancer Patients Travel Further for Equitable Surgical Care at a Comprehensive Cancer Center. Health equity Yang, R. L., Wapnir, I. 2018; 2 (1): 10916

Abstract

Purpose: Disparities in surgical breast cancer care have been documented for racial and ethnic minorities. On average, these minorities are less likely to utilize National Cancer Institute (NCI)-designated cancer centers and travel shorter distances to receive care. With the growing population of Hispanic patients in California, we analyzed the travel distance and surgical care of Hispanic and non-Hispanic patients at our large referral cancer center. Methods: Patients included were those who initiated treatment for a new diagnosis of ductal carcinoma in situ or invasive breast cancer at our NCI-designated cancer center during the period 2010-2014. Ethnicity was dichotomized as Hispanic and non-Hispanic. Google Maps were used to determine the distance from patient zip code to our institution, classified as 0-10, 10-30, 30-60, and >60 miles. Results: A total of 1765 non-Hispanic and 173 Hispanic patients were identified. Clinical stage by tumor size and nodal status were comparable between the two groups. Hispanic patients were younger (p<0.001) and more had Medicaid insurance (p<0.001). Hispanic patients traveled further when compared with non-Hispanics (p<0.001). In non-Hispanics and Hispanics, rates of breast conservation were 57.4% and 52.3% (p=0.30), unilateral mastectomy 34.2% and 36.2% (p=0.44), bilateral mastectomy 8.4% and 11.5% (p=0.24), and immediate postmastectomy reconstruction 42.6% and 50.6% (p=0.34), respectively. Hispanic ethnicity was not associated with different odds of receiving breast conservation (odds ratio [OR] 1.01, confidence interval [CI] 0.73-1.40), unilateral mastectomy (OR 1.05, CI 0.75-1.44), bilateral mastectomy (OR 1.37, CI 0.81-2.31), or immediate postmastectomy breast reconstruction (OR 1.27, CI 0.86-1.88), when compared with non-Hispanic ethnicity, after controlling for patient age, insurance status, and distance traveled. Conclusions: Surgical care was similar for Hispanic and non-Hispanic patients treated at our NCI-designated cancer center. However, this Hispanic population traveled further than non-Hispanic patients. Our findings suggest that accessibility to transportation and institutional practices are instrumental in delivering equitable breast cancer surgical care for Hispanic patients.

View details for PubMedID 30283856

Intraoperative Tumor Detection Using a Ratiometric Activatable Fluorescent Peptide: A First-in-Human Phase 1 Study (vol 24, pg 3167, 2017) ANNALS OF SURGICAL ONCOLOGY Unkart, J. T., Chen, S. L., Wapnir, I. L., Gonzalez, J. E., Harootunian, A., Wallace, A. M. 2017; 24: S693
Intraoperative Tumor Detection Using a Ratiometric Activatable Fluorescent Peptide: A First-in-Human Phase 1 Study ANNALS OF SURGICAL ONCOLOGY Unkart, J. T., Chen, S. L., Wapnir, I. L., Gonzalez, J. E., Harootunian, A., Wallace, A. M. 2017; 24 (11): 316773

Abstract

Positive surgical margins remain a significant challenge in breast cancer surgery. This report describes the use of a novel, first-in-human ratiometric activatable cell-penetrating peptide in breast cancer surgery.A two-part, multi-institutional phase 1 trial of AVB-620 with a 3+3 dose escalation and dose-expansion cohorts was conducted. The patients received an infusion of AVB-620 2-20h before planned lumpectomy/mastectomy and sentinel node biopsy/axillary dissection. Imaging analysis was performed on images obtained from the surgical field as well as post-excision surgical specimens. Pathology reports were obtained to correlate imaging results with histopathologic data. Information on physical adverse events and laboratory abnormalities were recorded.A total of 27 patients received infusion of AVB-620 and underwent surgical excision of breast cancer. The findings showed no adverse events or laboratory values attributable to infusion of AVB-620. The 8-mg dose was selected from the dose-escalation cohort for use with the expansion cohort based on imaging data. Region-of-interest (ROI) imaging analysis from the 8-mg cohort demonstrated measurable changes between pathology confirmed tumor-positive and tumor-negative tissue.Intraoperative imaging of surgical specimens after infusion with AVB-620 allowed for real-time tumor detection. Infusion of AVB-620 is safe and may improve intraoperative detection of malignant tissue during breast cancer operations.

View details for PubMedID 28699134

Chemotherapy (CT) for isolated locoregional recurrence (ILRR) of breast cancer in ER-positive (ER plus ) and ER-negative (ER-) cohorts: Final analysis of the CALOR trial Wapnir, I., Price, K. N., Anderson, S. J., Robidoux, A., Nortier, M. R., Paterson, A. G., Rimawi, M. F., Lang, I., Canada, J., Thurlimann, B. K., Mamounas, E. P., Geyer, C. E., Gelber, S. I., Coates, A. S., Gelber, R. D., Rastogi, P., Regan, M. M., Wolmark, N., Aebi, S. AMER SOC CLINICAL ONCOLOGY. 2017
Circulating tumor DNA and burden of disease in breast cancer Hoffman, A., Aleshin, A., Banks, K., Talasaz, A., Eltoukhy, H., Telli, M., Wapnir, I. SPRINGER. 2017: 3045
Molecular receptor profiles in male mutation carriers with breast cancer Wapnir, I., Kingham, K., Mills, M., Ford, J., Kurian, A. SPRINGER. 2017: 11213
Clinical Utility of the 12-Gene DCIS Score Assay: Impact on Radiotherapy Recommendations for Patients with Ductal Carcinoma In Situ ANNALS OF SURGICAL ONCOLOGY Manders, J. B., Kuerer, H. M., Smith, B. D., McCluskey, C., Farrar, W. B., Frazier, T. G., Li, L., Leonard, C. E., Carter, D. L., Chawla, S., Medeiros, L. E., Guenther, J. M., Castellini, L. E., Buchholz, D. J., Mamounas, E. P., Wapnir, I. L., Horst, K. C., Chagpar, A., Evans, S. B., Riker, A. I., Vali, F. S., Solin, L. J., Jablon, L., Recht, A., Sharma, R., Lu, R., Sing, A. P., Hwang, E. S., White, J. 2017; 24 (3): 660-668

Abstract

The aim of this study was to determine the impact of the results of the 12-gene DCIS Score assay on (i) radiotherapy recommendations for patients with pure ductal carcinoma in situ (DCIS) following breast-conserving surgery (BCS), and (ii) patient decisional conflict and state anxiety.Thirteen sites across the US enrolled patients (March 2014-August 2015) with pure DCIS undergoing BCS. Prospectively collected data included clinicopathologic factors, physician estimates of local recurrence risk, DCIS Score results, and pre-/post-assay radiotherapy recommendations for each patient made by a surgeon and a radiation oncologist. Patients completed pre-/post-assay decisional conflict scale and state-trait anxiety inventory instruments.The analysis cohort included 127 patients: median age 60years, 80% postmenopausal, median size 8mm (39% 5mm), 70% grade 1/2, 88% estrogen receptor-positive, 75% progesterone receptor-positive, 54% with comedo necrosis, and 18% multifocal. Sixty-six percent of patients had low DCIS Score results, 20% had intermediate DCIS Score results, and 14% had high DCIS Score results; the median result was 21 (range 0-84). Pre-assay, surgeons and radiation oncologists recommended radiotherapy for 70.9 and 72.4% of patients, respectively. Post-assay, 26.4% of overall recommendations changed, including 30.7 and 22.0% of recommendations by surgeons and radiation oncologists, respectively. Among patients with confirmed completed questionnaires (n=32), decision conflict (p=0.004) and state anxiety (p=0.042) decreased significantly from pre- to post-assay.Individualized risk estimates from the DCIS Score assay provide valuable information to physicians and patients. Post-assay, in response to DCIS Score results, surgeons changed treatment recommendations more often than radiation oncologists. Further investigation is needed to better understand how such treatment changes may affect clinical outcomes.

View details for DOI 10.1245/s10434-016-5583-7

View details for Web of Science ID 000394178600011

View details for PubMedCentralID PMC5306072

Poor Prognosis After Second Locoregional Recurrences in the CALOR Trial ANNALS OF SURGICAL ONCOLOGY Wapnir, I. L., Gelber, S., Anderson, S. J., Mamounas, E. P., Robidoux, A., Martin, M., Nortier, J. W., Geyer, C. E., Paterson, A. H., Lang, I., Price, K. N., Coates, A. S., Gelber, R. D., Rastogi, P., Regan, M. M., Wolmark, N., Aebi, S. 2017; 24 (2): 398-406

Abstract

Isolated locoregional recurrences (ILRRs) of breast cancer confer a significant risk for the development of distant metastasis. Management practices and second ILRR events in the Chemotherapy as Adjuvant for LOcally Recurrent breast cancer (CALOR) trial were investigated.In this study, 162 patients with ILRR were randomly assigned to receive postoperative chemotherapy or no chemotherapy. Descriptive statistics characterize outcomes according to local therapy and the influence of hormone receptor status on subsequent recurrences. Competing risk regression models, Kaplan-Meier estimates, and Cox proportional hazards models were used to evaluate associations between treatment, site of second recurrence, and outcome.The median follow-up period was 4.9 years. Of the 98 patients who received breast-conserving primary surgery 89 had an ipsilateral-breast tumor recurrence. Salvage mastectomy was performed for 73 patients and repeat lumpectomy for 16 patients. Another eight patients had nodal ILRR, and one patient had chest wall ILRR. Among 64 patients whose primary surgery was mastectomy, 52 had chest wall/skin ILRR, and 12 had nodal ILRR. For 15 patients, a second ILRR developed a median of 1.6 years (range 0.08-4.8 years) after ILRR. All second ILRRs occurred for patients with progesterone receptor-negative ILRR. Death occurred for 7 (47 %) of 15 patients with a second ILRR and 19 (51 %) of 37 patients with a distant recurrence. As shown in the multivariable analysis, the significant predictors of survival after either a second ILRR or distant recurrence were chemotherapy for the primary cancer (hazard ratio [HR], 3.55; 95 % confidence interval [CI], 1.15-10.9; p = 0.03) and the interval (continuous) from the primary surgery (HR, 0.87; 95 % CI, 0.75-1.00; p = 0.05).Second ILRRs represented about one third of all recurrence events after ILRR, and all were PR-negative. These second ILRRs and distant metastases portend an unfavorable outcome.

View details for DOI 10.1245/s10434-016-5571-y

View details for PubMedID 27663567

Will oncotype DX DCIS testing guide therapy? A single-institution correlation of oncotype DX DCIS results with histopathologic findings and clinical management decisions. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc Lin, C. Y., Mooney, K. n., Choy, W. n., Yang, S. R., Barry-Holson, K. n., Horst, K. n., Wapnir, I. n., Allison, K. n. 2017

Abstract

Given the increased detection rates of ductal carcinoma in situ (DCIS) and the limited overall survival benefit from adjuvant breast irradiation after breast-conserving surgery, there is interest in identifying subsets of patients who have low rates of ipsilateral breast tumor recurrence such that they might safely forgo radiation. The Oncotype DCIS score is a reverse transcription-PCR (RT-PCR)-based assay that was validated to predict which DCIS cases are most likely to recur. Clinically, these results may be used to assist in selecting which patients with DCIS might safely forgo radiation therapy after breast-conserving surgery; however, little is currently published on how this test is being used in practice. Our study examines traditional histopathologic features used in predicting DCIS risk with Oncotype DCIS results and how these results affect clinical decision-making at our academic institution. Histopathologic features and management decisions for 37 cases with Oncotype DCIS results over the past 4 years were collected. Necrosis, high nuclear grade, biopsy site change, estrogen receptor and progesterone receptor positivity <90% on immunohistochemistry, and Van Nuys Prognostic Index score of 8 or greater were significant predictors of an intermediate-high recurrence score on multivariate regression analysis (P<0.02). Low Oncotype DCIS scores and low nuclear grade were associated with lower rate of radiation therapy (P<0.008). There were seven cases (19%) with Oncotype DCIS results that we considered unexpected in relation to the histopathologic findings (ie, high nuclear grade with comedonecrosis and a low Oncotype score, or hormone receptor discrepancies). Overall, pathologic features correlate with Oncotype DCIS scores but unexpected results do occur, making individual recommendations sometimes challenging.Modern Pathology advance online publication, 15 December 2017; doi:10.1038/modpathol.2017.172.

View details for PubMedID 29243740

Erratum to: Intraoperative Tumor Detection Using a Ratiometric Activatable Fluorescent Peptide: A First-in-Human Phase 1 Study. Annals of surgical oncology Unkart, J. T., Chen, S. L., Wapnir, I. L., Gonzlez, J. E., Harootunian, A. n., Wallace, A. M. 2017; 24 (Suppl 3): 693

View details for PubMedID 28762115

Oncologic Procedures Amenable to Fluorescence-guided Surgery. Annals of surgery Tipirneni, K. E., Warram, J. M., Moore, L. S., Prince, A. C., de Boer, E., Jani, A. H., Wapnir, I. L., Liao, J. C., Bouvet, M., Behnke, N. K., Hawn, M. T., Poultsides, G. A., Vahrmeijer, A. L., Carroll, W. R., Zinn, K. R., Rosenthal, E. 2016

Abstract

Although fluorescence imaging is being applied to a wide range of cancers, it remains unclear which disease populations will benefit greatest. Therefore, we review the potential of this technology to improve outcomes in surgical oncology with attention to the various surgical procedures while exploring trial endpoints that may be optimal for each tumor type.For many tumors, primary treatment is surgical resection with negative margins, which corresponds to improved survival and a reduction in subsequent adjuvant therapies. Despite unfavorable effect on patient outcomes, margin positivity rate has not changed significantly over the years. Thus, patients often experience high rates of re-excision, radical resections, and overtreatment. However, fluorescence-guided surgery (FGS) has brought forth new light by allowing detection of subclinical disease not readily visible with the naked eye.We performed a systematic review of clinicatrials.gov using search terms "fluorescence," "image-guided surgery," and "near-infrared imaging" to identify trials utilizing FGS for those received on or before May 2016.fluorescence surgery for tumor debulking, wide local excision, whole-organ resection, and peritoneal metastases.fluorescence in situ hybridization, fluorescence imaging for lymph node mapping, nonmalignant lesions, nonsurgical purposes, or image guidance without fluorescence.Initial search produced 844 entries, which was narrowed down to 68 trials. Review of literature and clinical trials identified 3 primary resection methods for utilizing FGS: (1) debulking, (2) wide local excision, and (3) whole organ excision.The use of FGS as a surgical guide enhancement has the potential to improve survival and quality of life outcomes for patients. And, as the number of clinical trials rise each year, it is apparent that FGS has great potential for a broad range of clinical applications.

View details for DOI 10.1097/SLA.0000000000002127

View details for PubMedID 28045715

Society of Surgical Oncology-American Society for Radiation Oncology-American Society of Clinical Oncology Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Ductal Carcinoma In Situ JOURNAL OF CLINICAL ONCOLOGY Morrow, M., Van Zee, K. J., Solin, L. J., Houssami, N., Chavez-MacGregor, M., Harris, J. R., Horton, J., Hwang, S., Johnson, P. L., Marinovich, M. L., Schnitt, S. J., Wapnir, I., Moran, M. S. 2016; 34 (33): 4040-U166

Abstract

Controversy exists regarding the optimal negative margin width for ductal carcinoma in situ (DCIS) treated with breast-conserving surgery and whole-breast irradiation (WBRT).A multidisciplinary consensus panel used a meta-analysis of margin width and ipsilateral breast tumor recurrence (IBTR) from a systematic review of 20 studies including 7883 patients and other published literature as the evidence base for consensus.Negative margins halve the risk of IBTR compared with positive margins defined as ink on DCIS. A 2 mm margin minimizes the risk of IBTR compared with smaller negative margins. More widely clear margins do not significantly decrease IBTR compared with 2 mm margins. Negative margins less than 2 mm alone are not an indication for mastectomy, and factors known to impact rates of IBTR should be considered in determining the need for re-excision.The use of a 2 mm margin as the standard for an adequate margin in DCIS treated with WBRT is associated with low rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcome, and decrease health care costs. Clinical judgment should be used in determining the need for further surgery in patients with negative margins < 2 mm.

View details for DOI 10.1200/JCO.2016.68.3573

View details for PubMedID 27528719

Society of Surgical Oncology-American Society for Radiation Oncology-American Society of Clinical Oncology Consensus Guideline on Margins for Breast-Conserving Surgery with Whole-Breast Irradiation in Ductal Carcinoma In Situ ANNALS OF SURGICAL ONCOLOGY Morrow, M., Van Zee, K. J., Solin, L. J., Houssami, N., Chavez-MacGregor, M., Harris, J. R., Horton, J., Hwang, S., Johnson, P. L., Marinovich, M. L., Schnitt, S. J., Wapnir, I., Moran, M. S. 2016; 23 (12): 3801-3810

Abstract

Controversy exists regarding the optimal negative margin width for ductal carcinoma in situ (DCIS) treated with breast-conserving surgery and whole-breast irradiation.A multidisciplinary consensus panel used a meta-analysis of margin width and ipsilateral breast tumor recurrence (IBTR) from a systematic review of 20 studies including 7,883 patients and other published literature as the evidence base for consensus.Negative margins halve the risk of IBTR compared with positive margins defined as ink on DCIS. A 2-mm margin minimizes the risk of IBTR compared with smaller negative margins. More widely clear margins do not significantly decrease IBTR compared with 2-mm margins. Negative margins narrower than 2 mm alone are not an indication for mastectomy, and factors known to affect rates of IBTR should be considered in determining the need for re-excision.Use of a 2-mm margin as the standard for an adequate margin in DCIS treated with whole-breast irradiation is associated with lower rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs. Clinical judgment should be used in determining the need for further surgery in patients with negative margins narrower than 2 mm.

View details for DOI 10.1245/s10434-016-5449-z

View details for PubMedID 27527714

Clinical Utility of the 12-Gene DCIS Score Assay: Impact on Radiotherapy Recommendations for Patients with Ductal Carcinoma In Situ. Annals of surgical oncology Manders, J. B., Kuerer, H. M., Smith, B. D., McCluskey, C., Farrar, W. B., Frazier, T. G., Li, L., Leonard, C. E., Carter, D. L., Chawla, S., Medeiros, L. E., Guenther, J. M., Castellini, L. E., Buchholz, D. J., Mamounas, E. P., Wapnir, I. L., Horst, K. C., Chagpar, A., Evans, S. B., Riker, A. I., Vali, F. S., Solin, L. J., Jablon, L., Recht, A., Sharma, R., Lu, R., Sing, A. P., Hwang, E. S., White, J. 2016: -?

Abstract

The aim of this study was to determine the impact of the results of the 12-gene DCIS Score assay on (i) radiotherapy recommendations for patients with pure ductal carcinoma in situ (DCIS) following breast-conserving surgery (BCS), and (ii) patient decisional conflict and state anxiety.Thirteen sites across the US enrolled patients (March 2014-August 2015) with pure DCIS undergoing BCS. Prospectively collected data included clinicopathologic factors, physician estimates of local recurrence risk, DCIS Score results, and pre-/post-assay radiotherapy recommendations for each patient made by a surgeon and a radiation oncologist. Patients completed pre-/post-assay decisional conflict scale and state-trait anxiety inventory instruments.The analysis cohort included 127 patients: median age 60years, 80% postmenopausal, median size 8mm (39% 5mm), 70% grade 1/2, 88% estrogen receptor-positive, 75% progesterone receptor-positive, 54% with comedo necrosis, and 18% multifocal. Sixty-six percent of patients had low DCIS Score results, 20% had intermediate DCIS Score results, and 14% had high DCIS Score results; the median result was 21 (range 0-84). Pre-assay, surgeons and radiation oncologists recommended radiotherapy for 70.9 and 72.4% of patients, respectively. Post-assay, 26.4% of overall recommendations changed, including 30.7 and 22.0% of recommendations by surgeons and radiation oncologists, respectively. Among patients with confirmed completed questionnaires (n=32), decision conflict (p=0.004) and state anxiety (p=0.042) decreased significantly from pre- to post-assay.Individualized risk estimates from the DCIS Score assay provide valuable information to physicians and patients. Post-assay, in response to DCIS Score results, surgeons changed treatment recommendations more often than radiation oncologists. Further investigation is needed to better understand how such treatment changes may affect clinical outcomes.

View details for PubMedID 27704370

Lymph Node Ratio Analysis After Neoadjuvant Chemotherapy is Prognostic in Hormone Receptor-Positive and Triple-Negative Breast Cancer. Annals of surgical oncology Tsai, J., Bertoni, D., Hernandez-Boussard, T., Telli, M. L., Wapnir, I. L. 2016; 23 (10): 3310-3316

Abstract

Lymph node ratios (LNR), the proportion of positive lymph nodes over the number excised, both defined as ranges and single ratio values are prognostic of outcome. Little is known of the prognostic value of LNR after neoadjuvant chemotherapy (NAC) according to molecular subtype.From 2003 to 2014, patients who underwent definitive surgery after NAC were identified. LNR was calculated for node-positive patients who received axillary dissection or had at least 6 nodes removed. DFS was calculated using the Kaplan-Meier log rank test for yp N0-3 status, LNR categories (LNRC) 0.20 (low), 0.21-0.65 (intermediate), >0.65 (high), and single LNR values.Of 428 NAC recipients, 263 were node negative and 165 (38.6%) node positive: ypN1=97 (58.8%), ypN2=43 (26.1%), and ypN3=25 (15.2%). Among node-positive cancers, the median number of LN removed was 14 (range, 6-51) and the median LNR was 0.22 (range, 0.03-1.0). Nodal stage was inversely associated with 5-year DFS: 91.5% (ypN0), 74.5% (ypN1), 49.8% (ypN2), and 50.7% (ypN3) (p<0.001). LNRC was similarly inversely associated with DFS: 69.1% (low), 71.4% (intermediate), 49.3% (high) (p<0.001). Significant associations between LNRC and DFS were demonstrated in hormone receptor (HR)-positive and triple negative breast cancer (TNBC) subtypes, p=0.02 and p=0.003. A single-value LNR0.15 in node-positive, HR-positive (94.1 vs 67.7%; p=0.04) and TNBC (94.1 vs 47.8%; p=0.001) groups was also significant.Residual nodal disease after NAC, analyzed by LNRC or LNR=0.15 cutoff value, is prognostic and can discriminate between favorable and unfavorable outcomes for HR-positive and TNBC cancers.

View details for DOI 10.1245/s10434-016-5319-8

View details for PubMedID 27401442

Breast Cancer Survivorship: Why, What and When? Annals of surgical oncology Gass, J., Dupree, B., Pruthi, S., Radford, D., Wapnir, I., Antoszewska, R., Curtis, A., Johnson, N. 2016; 23 (10): 3162-3167

Abstract

Survivorship medicine is fairly new in the realm of oncology. As we broaden our focus from treatment and prevention to include survivorship there is substantial opportunity to enhance the care of the patient. Important in successful management of recovery after cancer treatment is managing the side effects of therapy and improving quality of life. This ranges from sexual dysfunction, depression to lymphedema. Guideline-based surveillance after treatment with clear communication of care plans to the patient and their providers, especially primary care, is paramount. Thoughtful pre-surgical treatment planning, which may include neoadjuvant approaches or consideration of fertility preservation, results in superior long-term patient outcomes. Understanding the importance of the teachable moment in effecting behavioral and lifestyle changes that reduce risk of recurrence is also an essential component of excellent cancer survivor patient care. We identified the following areas for focus as they represent the key areas for accreditation and patient driven needs. Development of survivorship plans, post treatment surveillance, sexuality and fertility preservation, lymphedema management and risk reduction lifestyle and behavioral changes.

View details for DOI 10.1245/s10434-016-5403-0

View details for PubMedID 27431417

Rising Bilateral Mastectomy Rates Among Neoadjuvant Chemotherapy Recipients in California From 1998 to 2012. Annals of surgery Wapnir, I. L., Kurian, A. W., Lichtensztajn, D. Y., Clarke, C. A., Gomez, S. L. 2016: -?

Abstract

To study the impact of rising bilateral mastectomy rates among neoadjuvant chemotherapy (NAC) recipients in California.NAC for operable breast cancer (BC) can downstage disease and facilitate breast conservation. We assessed trends in NAC use and surgical procedures in California from January 1, 1998 to December 31, 2012 using statewide population-based cancer registry data.A total of 236,797 females diagnosed with stage I-III BC were studied. Information regarding NAC, adjuvant chemotherapy (aCT), breast conserving surgery (BCS), bilateral mastectomy (BLM), and unilateral mastectomy (ULM) was abstracted from the medical records. Multivariable polytomous logistic regression was used to estimate odds ratios (OR) of receiving NAC and of type of surgery after NAC.Approximately, 40.1% (94,980) of patients received chemotherapy: 87% (82,588) aCT and 13.0% (12,392) NAC. NAC use more than doubled over time and increased with stage (Stage I, 0.7%; Stage III, 29.9%). Multivariable predictors of NAC treatment were stage (III), younger age (<40 yrs), Black or Hispanic race/ethnicity versus non-Hispanic White (OR 1.10, 95% confidence interval (CI) 1.05-1.16), and care at a National Cancer Institute (NCI)-designated center (OR 1.70, CI 1.58-1.82). Most NAC recipients (68.4%) had mastectomies, and 14.3% of them underwent BLM. In contrast, 47.9% aCT patients had mastectomies with 7.3% BLM. The only independent predictor of BCS after NAC was care at a NCI-designated center (OR 1.28, CI 1.10-1.49), and of BLM, age <40 years versus 50 to 64 years (OR 2.59, CI 2.21-3.03), or residence in the highest socioeconomic neighborhood quintile versus lowest (OR 2.10, CI 1.67-2.64).NAC use remains low. Predictors of surgery type after NAC were sociodemographic rather than clinical, raising concern for disparities in care access.

View details for PubMedID 27611617

Society of Surgical Oncology-American Society for Radiation Oncology-American Society of Clinical Oncology Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Ductal Carcinoma in Situ. Practical radiation oncology Morrow, M., Van Zee, K. J., Solin, L. J., Houssami, N., Chavez-MacGregor, M., Harris, J. R., Horton, J., Hwang, S., Johnson, P. L., Marinovich, M. L., Schnitt, S. J., Wapnir, I., Moran, M. S. 2016; 6 (5): 287-295

Abstract

Controversy exists regarding the optimal negative margin width for ductal carcinoma in situ (DCIS) treated with breast-conserving surgery and whole-breast irradiation.A multidisciplinary consensus panel used a meta-analysis of margin width and ipsilateral breast tumor recurrence (IBTR) from a systematic review of 20 studies including 7883 patients and other published literature as the evidence base for consensus.Negative margins halve the risk of IBTR compared with positive margins defined as ink on DCIS. A 2-mm margin minimizes the risk of IBTR compared with smaller negative margins. More widely clear margins do not significantly decrease IBTR compared with 2-mm margins. Negative margins narrower than 2 mm alone are not an indication for mastectomy, and factors known to affect rates of IBTR should be considered in determining the need for re-excision.Use of a 2-mm margin as the standard for an adequate margin in DCIS treated with whole-breast irradiation is associated with lower rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs. Clinical judgment should be used in determining the need for further surgery in patients with negative margins narrower than 2 mm.

View details for DOI 10.1016/j.prro.2016.06.011

View details for PubMedID 27538810

Regression of experimental NIS-expressing breast cancer brain metastases in response to radioiodide/gemcitabine dual therapy ONCOTARGET Renier, C., Do, J., Reyna-Neyra, A., Foster, D., De, A., Vogel, H., Jeffrey, S. S., Tse, V., Carrasco, N., Wapnir, I. 2016; 7 (34): 54811-54824

Abstract

Treating breast cancer brain metastases (BCBMs) is challenging. Na+/I- symporter (NIS) expression in BCBMs would permit their selective targeting with radioiodide (131I-). We show impressive enhancement of tumor response by combining131I- with gemcitabine (GEM), a cytotoxic radiosensitizer. Nude mice mammary fat-pad (MFP) tumors and BCBMs were generated with braintropic MDA-MB-231Br cells transduced with bicistronically-linked NIS and firefly luciferase cDNAs. Response was monitored in vivo via bioluminescent imaging and NIS tumor expression.131I-/GEM therapy inhibited MFP tumor growth more effectively than either agent alone. BCBMs were treated with: high or low-dose GEM (58 or 14.5 mg/Kg4); 131I- (1mCi or 20.5 mCi 7 days apart); and 131I-/GEM therapy. By post-injection day (PID) 25, 82-86% of controls and 78-83% of 131I--treated BCBM grew, whereas 17% low-dose and 36% high-dose GEM regressed. The latter tumors were smaller than the controls with comparable NIS expression (~20% of cells). High and low-dose 131I-/ GEM combinations caused 89% and 57% tumor regression, respectively. High-dose GEM/131I- delayed tumor growth: tumors increased 5-fold in size by PID45 (controls by PID18). Although fewer than 25% of cells expressed NIS, GEM/131I- caused dramatic tumor regression in NIS-transduced BCBMs. This effect was synergistic, and supports the hypothesis that GEM radiosensitizes cells to 131I-.

View details for DOI 10.18632/oncotarget.10238

View details for Web of Science ID 000385435000059

Protecting Nipple Perfusion by Devascularization and Surgical Delay in Patients at Risk for Ischemic Complications During Nipple-Sparing Mastectomies ANNALS OF SURGICAL ONCOLOGY Bertoni, D. M., Dung Nguyen, D., Rochlin, D., Hernandez-Boussard, T., Meyer, S., Choy, N., Gurtner, G. C., Wapnir, I. L. 2016; 23 (8): 2665-2672

Abstract

Indications for nipple-sparing mastectomy (NSM) are expanding; however, high-risk patients have more ischemic complications. Surgical devascularization of the nipple-areolar complex (NAC) prior to NSM can reduce complications. This study reports perfusion patterns and complications in high-risk patients undergoing 2-stage NSM.Surgical devascularization of the NAC was performed 3-6weeks prior to NSM in 28 women. Risk factors included ptosis, obesity, smoking, prior breast surgery, and radiation. Using indocyanine green (ICG)-based fluorescence and an infrared camera, blood inflow was visualized intraoperatively. NAC perfusion patterns were classified as: V1, underlying breast; V2, surrounding skin; V3=V1+V2, or V4, capillary fill following devascularization. Ischemic complications were analyzed.Baseline perfusion for 54 breasts was 35% V1, 32% V2, and 33% V3. Increasing ptosis was associated with V1 pattern: 86% for grade 3, 31% for grade 2, and 18% for grade 1. Postdevascularization epidermolysis was observed in 63% of V1 baseline, 41% of V2, and 22% of V3 (P=.042) and after NSM in 26% for V1, 7% for V2, and 6% for V3 (P=.131). Ptosis was significantly associated with epidermolysis postdevascularization (P=.002) and NSM (P=.002). Smoking and BMI 30 were related to increased ischemic complications. Two or more risk factors were associated with postdevascularization ischemic changes (P=.026), but were not significant after NSM. Nipple loss was not observed, but 2 patients underwent partial areolar resection.Adaptive circulatory changes after devascularization allow tissues to tolerate the additional ischemic challenge of mastectomy. Our findings support extending 2-staged operations to high-risk women previously considered unsuitable for NSM.

View details for DOI 10.1245/s10434-016-5201-8

View details for PubMedID 27038458

Relationship between rising bilateral mastectomy rates and increased use of neoadjuvant chemotherapy (NAC) in California, 1998-2012. Wapnir, I., Kurian, A. W., Lichtensztajn, D., Clarke, C. A., Gomez, S. AMER SOC CLINICAL ONCOLOGY. 2016
Addressing Inherited Predisposition for Breast Cancer in Transplant Recipients JOURNAL OF SURGICAL ONCOLOGY Yang, R. L., Kurian, A. W., Winton, L. M., Weill, D., Patel, K., Kingham, K., Wapnir, I. L. 2016; 113 (6): 605-608

Abstract

Consideration of prophylactic mastectomy surgery following transplantation requires complex medical decision-making, and bias against elective surgery exists because of concern for post-operative complications. Prevention of cancer in transplant recipients is of utmost importance, given the risks of treating malignancy in an immunosuppressed patient. We present a patient case and review of the literature to support a thorough pre-transplantation evaluation of family history and consideration of prophylactic interventions to safeguard the quality of life of transplant recipients. J. Surg. Oncol. 2016 Wiley Periodicals, Inc.

View details for DOI 10.1002/jso.24193

View details for PubMedID 26861253

(527) An internet-based perioperative pain psychology treatment program: results of a randomized controlled trial in breast oncology surgery patients. journal of pain Darnall, B., Wheeler, A., Taub, C., MACKEY, I., Wapnir, I., Schultz, C., RICO, T., Flood, P. 2016; 17 (4S): S106-?

View details for DOI 10.1016/j.jpain.2016.01.334

View details for PubMedID 28162332

Disease-Free Survival Using Lymph Node Ratio Analysis After Neoadjuvant Chemotherapy Tsai, J., Bertoni, D., Tsai, C., Hernandez-Boussard, T., Wapnir, I. SPRINGER. 2016: 16263
Surgical Breast Cancer Care for Hispanic Patients Who Travel to an Academic Cancer Center Yang, R., Rhoads, K., Wapnir, I. SPRINGER. 2016: 17273
The 12-gene DCIS score assay: Impact on radiation treatment (XRT) recommendations and clinical utility Manders, J. B., Kuerer, H. M., Smith, B. D., McCluskey, C., Farrar, W. B., Frazier, T. G., Li, L., Leonard, C. E., Carter, D. L., Chawla, S., Medeiros, L. E., Guenther, J. M., Castellini, L. E., Buchholz, D. J., Mamounas, E. P., Wapnir, I. L., Horst, K. C., Chagpar, A., Evans, S. B., Riker, A. I., Vali, F. S., Solin, L. J., Jablon, L., Recht, A., Sharma, R., Lu, R., Sing, A. P., Hwang, E. S., White, J. AMER ASSOC CANCER RESEARCH. 2016
A technique for preoperative axillary lymph node tattooing in patients with breast cancer Wapnir, I. L., Downey, J. R., Lipson, J. A., Ikeda, D. M. AMER ASSOC CANCER RESEARCH. 2016
Rising bilateral mastectomy rates among neoadjuvant chemotherapy recipients in California, 1998-2012 Annals of Surgery Wapnirr, I., Kurian, A. 2016

Abstract

Treating breast cancer brain metastases (BCBMs) is challenging. Na+/I- symporter (NIS) expression in BCBMs would permit their selective targeting with radioiodide (131I-). We show impressive enhancement of tumor response by combining131I- with gemcitabine (GEM), a cytotoxic radiosensitizer. Nude mice mammary fat-pad (MFP) tumors and BCBMs were generated with braintropic MDA-MB-231Br cells transduced with bicistronically-linked NIS and firefly luciferase cDNAs. Response was monitored in vivo via bioluminescent imaging and NIS tumor expression.131I-/GEM therapy inhibited MFP tumor growth more effectively than either agent alone. BCBMs were treated with: high or low-dose GEM (58 or 14.5 mg/Kg4); 131I- (1mCi or 20.5 mCi 7 days apart); and 131I-/GEM therapy. By post-injection day (PID) 25, 82-86% of controls and 78-83% of 131I--treated BCBM grew, whereas 17% low-dose and 36% high-dose GEM regressed. The latter tumors were smaller than the controls with comparable NIS expression (~20% of cells). High and low-dose 131I-/ GEM combinations caused 89% and 57% tumor regression, respectively. High-dose GEM/131I- delayed tumor growth: tumors increased 5-fold in size by PID45 (controls by PID18). Although fewer than 25% of cells expressed NIS, GEM/131I- caused dramatic tumor regression in NIS-transduced BCBMs. This effect was synergistic, and supports the hypothesis that GEM radiosensitizes cells to 131I-.

View details for PubMedID 27363025

rising bilateral mastectomy rates among neoadjuvant chemotherapy recipients in California, 1998-2012 Annals of Surgery Wapnir, I. 2016

Abstract

The superior aesthetic outcomes of nipple-sparing mastectomies (NSM) explain their increased use and rising popularity. Fortunately, cancer recurrences involving the nipple-areolar complex (NAC) have been reassuringly low in the range of 1%. Technical considerations and challenges of this procedure are centered on nipple ischemia and necrosis. Patient selection, reconstructive strategies and incision placement have lowered ischemic complications. In this context, rates of full NAC necrosis are 3% or less. The emergence of noninvasive tissue angiography provides surgeons with a practical tool to assess real-time breast skin and NAC perfusion. Herein, we review our classification system of NAC perfusion patterns defined as V1 (from subjacent breast), V2 (surrounding skin), and V3 (combination of V1 + V2). Additionally, we describe the benefits of a first stage operation to devascularize the NAC as a means of improving blood flow to the NAC in preparation for NSM, helping extend the use of NSM to more women. Intraoperative evaluation of skin perfusion allows surgeons to detect ischemia and modify the operative approach to optimize outcomes.

View details for DOI 10.3978/j.issn.2227-684X.2015.04.15

View details for PubMedID 26645004

Regression of experimental NIS-expressing breast cancer brain metastases in response to radioiodide/gemcitabine dual therapy. Oncotarget Renier, C. n., Do, J. n., Reyna-Neyra, A. n., Foster, D. n., De, A. n., Vogel, H. n., Jeffrey, S. S., Tse, V. n., Carrasco, N. n., Wapnir, I. n. 2016
Using intraoperative laser angiography to safeguard nipple perfusion in nipple-sparing mastectomies. Gland surgery Dua, M. M., Bertoni, D. M., Nguyen, D., Meyer, S., Gurtner, G. C., Wapnir, I. L. 2015; 4 (6): 497-505

Abstract

This study was designed to assess efficacy, safety, and predictors of response to iniparib in combination with gemcitabine and carboplatin in early-stage triple-negative and BRCA1/2 mutation-associated breast cancer.This single-arm phase II study enrolled patients with stage I to IIIA (T 1 cm) estrogen receptor-negative ( 5%), progesterone receptor-negative ( 5%), and human epidermal growth factor receptor 2-negative or BRCA1/2 mutation-associated breast cancer. Neoadjuvant gemcitabine (1,000 mg/m(2) intravenously [IV] on days 1 and 8), carboplatin (area under curve of 2 IV on days 1 and 8), and iniparib (5.6 mg/kg IV on days 1, 4, 8, and 11) were administered every 21 days for four cycles, until the protocol was amended to six cycles. The primary end point was pathologic complete response (no invasive carcinoma in breast or axilla). All patients underwent comprehensive BRCA1/2 genotyping, and homologous recombination deficiency was assessed by loss of heterozygosity (HRD-LOH) in pretreatment core breast biopsies.Among 80 patients, median age was 48 years; 19 patients (24%) had germline BRCA1 or BRCA2 mutations; clinical stage was I (13%), IIA (36%), IIB (36%), and IIIA (15%). Overall pathologic complete response rate in the intent-to-treat population (n = 80) was 36% (90% CI, 27 to 46). Mean HRD-LOH scores were higher in responders compared with nonresponders (P = .02) and remained significant when BRCA1/2 germline mutations carriers were excluded (P = .021).Preoperative combination of gemcitabine, carboplatin, and iniparib is active in the treatment of early-stage triple-negative and BRCA1/2 mutation-associated breast cancer. The HRD-LOH assay was able to identify patients with sporadic triple-negative breast cancer lacking a BRCA1/2 mutation, but with an elevated HRD-LOH score, who achieved a favorable pathologic response. Confirmatory controlled trials are warranted.

View details for DOI 10.1200/JCO.2014.57.0085

View details for PubMedID 25847929

Lymph node ratio as prognostic after neoadjuvant therapy in breast cancer. Bertoni, D., Hernandez-Boussard, T., Wapnir, I. AMER SOC CLINICAL ONCOLOGY. 2015

Abstract

This study was designed to assess efficacy, safety, and predictors of response to iniparib in combination with gemcitabine and carboplatin in early-stage triple-negative and BRCA1/2 mutation-associated breast cancer.This single-arm phase II study enrolled patients with stage I to IIIA (T 1 cm) estrogen receptor-negative ( 5%), progesterone receptor-negative ( 5%), and human epidermal growth factor receptor 2-negative or BRCA1/2 mutation-associated breast cancer. Neoadjuvant gemcitabine (1,000 mg/m(2) intravenously [IV] on days 1 and 8), carboplatin (area under curve of 2 IV on days 1 and 8), and iniparib (5.6 mg/kg IV on days 1, 4, 8, and 11) were administered every 21 days for four cycles, until the protocol was amended to six cycles. The primary end point was pathologic complete response (no invasive carcinoma in breast or axilla). All patients underwent comprehensive BRCA1/2 genotyping, and homologous recombination deficiency was assessed by loss of heterozygosity (HRD-LOH) in pretreatment core breast biopsies.Among 80 patients, median age was 48 years; 19 patients (24%) had germline BRCA1 or BRCA2 mutations; clinical stage was I (13%), IIA (36%), IIB (36%), and IIIA (15%). Overall pathologic complete response rate in the intent-to-treat population (n = 80) was 36% (90% CI, 27 to 46). Mean HRD-LOH scores were higher in responders compared with nonresponders (P = .02) and remained significant when BRCA1/2 germline mutations carriers were excluded (P = .021).Preoperative combination of gemcitabine, carboplatin, and iniparib is active in the treatment of early-stage triple-negative and BRCA1/2 mutation-associated breast cancer. The HRD-LOH assay was able to identify patients with sporadic triple-negative breast cancer lacking a BRCA1/2 mutation, but with an elevated HRD-LOH score, who achieved a favorable pathologic response. Confirmatory controlled trials are warranted.

View details for DOI 10.1200/JCO.2014.57.0085

View details for Web of Science ID 000355999800009

View details for PubMedID 25847929

Phase II Study of Gemcitabine, Carboplatin, and Iniparib As Neoadjuvant Therapy for Triple-Negative and BRCA1/2 Mutation-Associated Breast Cancer With Assessment of a Tumor-Based Measure of Genomic Instability: PrECOG 0105. Journal of clinical oncology Telli, M. L., Jensen, K. C., Vinayak, S., Kurian, A. W., Lipson, J. A., Flaherty, P. J., Timms, K., Abkevich, V., Schackmann, E. A., Wapnir, I. L., Carlson, R. W., Chang, P., Sparano, J. A., Head, B., Goldstein, L. J., Haley, B., Dakhil, S. R., Reid, J. E., Hartman, A., Manola, J., Ford, J. M. 2015; 33 (17): 1895-1901
Phase II Study of Gemcitabine, Carboplatin, and Iniparib As Neoadjuvant Therapy for Triple-Negative and BRCA1/2 Mutation-Associated Breast Cancer With Assessment of a Tumor-Based Measure of Genomic Instability: PrECOG 0105 JOURNAL OF CLINICAL ONCOLOGY Telli, M. L., Jensen, K. C., Vinayak, S., Kurian, A. W., Lipson, J. A., Flaherty, P. J., Timms, K., Abkevich, V., Schackmann, E. A., Wapnir, I. L., Carlson, R. W., Chang, P., Sparano, J. A., Head, B., Goldstein, L. J., Haley, B., Dakhil, S. R., Reid, J. E., Hartman, A., Manola, J., Ford, J. M. 2015; 33 (17): 1895-U57
Nipple Perfusion Is Preserved by Staged Devascularization in High-Risk Nipple-Sparing Mastectomies Bertoni, D. M., Nguyen, D., Rochlin, D., Choy, N., Gurtner, G., Wapnir, I. SPRINGER. 2015: 3536

Abstract

Pretreatment evaluation of axillary lymph nodes (ALNs) and marking of biopsied nodes in patients with newly diagnosed breast cancer is becoming routine practice. We sought to test tattooing of biopsied ALNs with a sterile black carbon suspension (Spot). The intraoperative success of identifying tattooed ALNs and their concordance to sentinel nodeswas determined.Women with suspicious ALNs and newly diagnosed breast cancer underwent palpation and/or ultrasound-guided fine needle aspiration or core needle biopsy, followed by injection of 0.1to0.5ml of Spot ink into the cortex of ALNs and adjacent soft tissue. Group I underwent surgery first, and group II underwent neoadjuvant therapy followed by surgery. Identification of black pigment and concordance between sentinel and tattooed nodes was evaluated.Twenty-eight patients were tattooed, 16 in group I and 12 in group II. Seventeen cases had evidence of atypia or metastases, 8 (50%) in group I and 9 (75%) in group II. Average number of days from tattooing to surgery was 22.9 (group I) and 130 (group II). Black tattoo ink was visualized intraoperatively in all cases, except one case with microscopic black pigment only. Fourteen group I and 10 group II patients had black pigment on histological examination of ALNs. Sentinel nodes corresponded to tattooed nodes in all except one group I patient with a tattooed non-sentinel node.Tattooed nodes are visible intraoperatively, even months later. This approach obviates the need for additional localization procedures during axillary staging.

View details for DOI 10.1245/s10434-014-4034-6

View details for PubMedID 25164040

Correlation of percutaneously biopsied axillary lymph nodes marked with black tattoo ink prior to neoadjuvant chemotherapy with sentinel lymph nodes in breast cancer patients Choy, N., Lipson, J., Pal, S., Ikeda, D., Trinh, L., Allison, K., Ozawa, M., Wheeler, A., Wapnir, I. AMER ASSOC CANCER RESEARCH. 2015
Initial results with preoperative tattooing of biopsied axillary lymph nodes and correlation to sentinel lymph nodes in breast cancer patients. Annals of surgical oncology Choy, N., Lipson, J., Porter, C., Ozawa, M., Kieryn, A., Pal, S., Kao, J., Trinh, L., Wheeler, A., Ikeda, D., Jensen, K., Allison, K., Wapnir, I. 2015; 22 (2): 377-382
Is Lymph Node Ratio Prognostic after Neoadjuvant Therapy for Breast Cancer? Bertoni, D. M., Hernandez-Boussard, T., Wapnir, I. L. SPRINGER. 2015: S52
Maastricht Delphi Consensus on Event Definitions for Classification of Recurrence in Breast Cancer Research Moossdorff, M., Van Roozendaal, L. M., Strobbe, L. J., Aebi, S., Cameron, D. A., Dixon, M., Giuliano, A. E., Haffty, B. G., Hickey, B. E., Hudis, C., Klimberg, S., Koczwara, B., Kuhn, T., Lippman, M., Lucci, A., Piccart, M., Smith, B. D., Tjan-Heijnen, V. C., Van der Velde, C. J., Van Zee, K. J., Vermorken, J. B., Viale, G., Wapnir, I. L., Voogd, A., White, J. R., Smidt, M. L. SPRINGER. 2015: S132

Abstract

Although rare, neuroendocrine carcinoma of the breast (NECB) is becoming an increasingly recognized entity. The current literature is limited to case reports and small series and therefore a comprehensive population-based analysis was conducted to investigate the clinicopathologic features and long-term outcomes associated with NECB. We included all patients in the SEER Database from 2003 to 2010 with a diagnosis of NECB. The 2012 WHO classification system was used to categorize patients based on histopathologic diagnosis: well-differentiated neuroendocrine tumors, small/oat cell or poorly differentiated neuroendocrine tumors, adenocarcinoma with neuroendocrine features (ANF), large cell neuroendocrine and carcinoid tumors. Survival analysis was performed for disease specific (DSS) and overall (OS) survival. Of the 284 cases identified, 52.1% were classified as well-differentiated, 25.7% small cell, 14.8% ANF, 4.9% large cell, and 2.5% carcinoid. In general, patients presented with advanced disease: 36.2% had positive lymph node metastases and 20.4% presented with systemic metastases. Five-year DSS rates for stage I-IV NECB were 88.1, 67.8, 60.5, and 12.4%, respectively, while five-year OS rates were 77.9, 57.3, 52.9, and 8.9%, respectively. DSS and OS were significantly different for well-differentiated neuroendocrine tumors and ANFs compared to small cell and carcinoid tumors. On univariate Cox proportional hazards regression, small cell carcinoma was significantly associated with worse DSS (OR 1.97, 95% CI 1.05-3.67) and OS (OR 2.66, 95% CI 1.49-4.72) compared to other neuroendocrine tumors. NECB is associated with advanced stage disease at presentation and an unfavorable prognosis for stage II-IV disease and small cell, large cell, and carcinoid histologic subtypes.

View details for DOI 10.1007/s10549-014-3207-0

View details for Web of Science ID 000345370600018

Dose-Escalated, Intratumoral TLR9 Agonist and Low-Dose Radiation Induce Abscopal Effects in Follicular Lymphoma Kohrt, H. E., Chu, J., Brody, J., Czerwinski, D. K., Chester, C., Sadaram, M., Advani, R., Kim, Y. H., Hoppe, R. T., Knox, S. J., Wapnir, I., Tibshirani, R. J., Levy, R. AMER SOC HEMATOLOGY. 2014

Abstract

Although rare, neuroendocrine carcinoma of the breast (NECB) is becoming an increasingly recognized entity. The current literature is limited to case reports and small series and therefore a comprehensive population-based analysis was conducted to investigate the clinicopathologic features and long-term outcomes associated with NECB. We included all patients in the SEER Database from 2003 to 2010 with a diagnosis of NECB. The 2012 WHO classification system was used to categorize patients based on histopathologic diagnosis: well-differentiated neuroendocrine tumors, small/oat cell or poorly differentiated neuroendocrine tumors, adenocarcinoma with neuroendocrine features (ANF), large cell neuroendocrine and carcinoid tumors. Survival analysis was performed for disease specific (DSS) and overall (OS) survival. Of the 284 cases identified, 52.1% were classified as well-differentiated, 25.7% small cell, 14.8% ANF, 4.9% large cell, and 2.5% carcinoid. In general, patients presented with advanced disease: 36.2% had positive lymph node metastases and 20.4% presented with systemic metastases. Five-year DSS rates for stage I-IV NECB were 88.1, 67.8, 60.5, and 12.4%, respectively, while five-year OS rates were 77.9, 57.3, 52.9, and 8.9%, respectively. DSS and OS were significantly different for well-differentiated neuroendocrine tumors and ANFs compared to small cell and carcinoid tumors. On univariate Cox proportional hazards regression, small cell carcinoma was significantly associated with worse DSS (OR 1.97, 95% CI 1.05-3.67) and OS (OR 2.66, 95% CI 1.49-4.72) compared to other neuroendocrine tumors. NECB is associated with advanced stage disease at presentation and an unfavorable prognosis for stage II-IV disease and small cell, large cell, and carcinoid histologic subtypes.

View details for DOI 10.1007/s10549-014-3207-0

View details for PubMedID 25399232

Impact of histological subtype on long-term outcomes of neuroendocrine carcinoma of the breast BREAST CANCER RESEARCH AND TREATMENT Cloyd, J. M., Yang, R. L., Allison, K. H., Norton, J. A., Hernandez-Boussard, T., Wapnir, I. L. 2014; 148 (3): 637-644

Abstract

Sentinel lymph node (SLN) biopsy has become the standard method of determining regional lymph node involvement in cutaneous melanoma. Although traditionally performed via injection of radioisotope tracers and blue dyes, fluorescent lymphangiography with indocyanine green (ICG) is an attractive alternative.Fifty two consecutive patients with cutaneous melanoma of the trunk or extremities underwent SLNB. Preoperative lymphoscintigraphy was performed with technetium-99m sulfur colloid (TSC). Peritumoral intradermal injection of isosulfan blue (ISB) and ICG was then performed. Successful identification of a sentinel lymph node via each modality was then assessed.A total of 77 lymph nodes were identified from the 52 patients (range 1-3). The majority of melanomas were extremity-based, superficial spreading type, and had SLN localized to the axilla. There were no complications related to IcG administration. Rates of SLN detection were 96.2% for TSC, 59.6% for ISB, and 88.5% for IcG (P<0.05 for ICG vs ISB). On univariate logistic regression analysis, no factors were found to be associated with failure of ICG.Fluorescent lymphangiography using ICG is an effective method of SLN identification in patients with cutaneous melanoma of the trunk and extremities. When ICG and TSC are used in combination, ISB offers no additional advantage and may be safely omitted. J. Surg. Oncol. 2014 Wiley Periodicals, Inc.

View details for DOI 10.1002/jso.23745

View details for PubMedID 25124992

Impact of histological subtype on long-term outcomes of neuroendocrine carcinoma of the breast. Breast cancer research and treatment Cloyd, J. M., Yang, R. L., Allison, K. H., Norton, J. A., Hernandez-Boussard, T., Wapnir, I. L. 2014; 148 (3): 637-644

Abstract

In breast cancer studies, many different endpoints are used. Definitions are often not provided or vary between studies. For instance, "local recurrence" may include different components in similar studies. This limits transparency and comparability of results. This project aimed to reach consensus on the definitions of local event, second primary breast cancer, regional and distant event for breast cancer studies.The RAND-UCLA Appropriateness method (modified Delphi method) was used. A Consensus Group of international breast cancer experts was formed, including representatives of all involved clinical disciplines. Consensus was reached in two rounds of online questionnaires and one meeting.Twenty-four international breast cancer experts participated. Consensus was reached on 134 items in four categories. Local event is defined as any epithelial breast cancer or ductal carcinoma in situ (DCIS) in the ipsilateral breast, or skin and subcutaneous tissue on the ipsilateral thoracic wall. Second primary breast cancer is defined as epithelial breast cancer in the contralateral breast. Regional events are breast cancer in ipsilateral lymph nodes. A distant event is breast cancer in any other location. Therefore, this includes metastasis in contralateral lymph nodes and breast cancer involving the sternal bone. If feasible, tissue sampling of a first, solitary, lesion suspected for metastasis is highly recommended.This project resulted in consensus-based event definitions for classification of recurrence in breast cancer research. Future breast cancer research projects should adopt these definitions to increase transparency. This should facilitate comparison of results and conducting reviews as well as meta-analysis.

View details for DOI 10.1093/jnci/dju288

View details for Web of Science ID 000348593200017

View details for PubMedID 25381395

Indocyanine green and fluorescence lymphangiography for sentinel lymph node identification in cutaneous melanoma. Journal of surgical oncology Cloyd, J. M., Wapnir, I. L., Read, B. M., Swetter, S., Greco, R. S. 2014; 110 (7): 888-892

Abstract

Sentinel lymph node (SLN) biopsy has become the standard method of determining regional lymph node involvement in cutaneous melanoma. Although traditionally performed via injection of radioisotope tracers and blue dyes, fluorescent lymphangiography with indocyanine green (ICG) is an attractive alternative.Fifty two consecutive patients with cutaneous melanoma of the trunk or extremities underwent SLNB. Preoperative lymphoscintigraphy was performed with technetium-99m sulfur colloid (TSC). Peritumoral intradermal injection of isosulfan blue (ISB) and ICG was then performed. Successful identification of a sentinel lymph node via each modality was then assessed.A total of 77 lymph nodes were identified from the 52 patients (range 1-3). The majority of melanomas were extremity-based, superficial spreading type, and had SLN localized to the axilla. There were no complications related to IcG administration. Rates of SLN detection were 96.2% for TSC, 59.6% for ISB, and 88.5% for IcG (P<0.05 for ICG vs ISB). On univariate logistic regression analysis, no factors were found to be associated with failure of ICG.Fluorescent lymphangiography using ICG is an effective method of SLN identification in patients with cutaneous melanoma of the trunk and extremities. When ICG and TSC are used in combination, ISB offers no additional advantage and may be safely omitted. J. Surg. Oncol. 2014 Wiley Periodicals, Inc.

View details for DOI 10.1002/jso.23745

View details for Web of Science ID 000344552200020

Maastricht Delphi Consensus on Event Definitions for Classification of Recurrence in Breast Cancer Research JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE Moossdorff, M., van Roozendaal, L. M., Strobbe, L. J., Aebi, S., Cameron, D. A., Dixon, J. M., Giuliano, A. E., Haffty, B. G., Hickey, B. E., Hudis, C. A., Klimberg, V. S., Koczwara, B., Kuehn, T., Lippman, M. E., Lucci, A., Piccart, M., Smith, B. D., Tjan-Heijnen, V. C., van de Velde, C. J., Van Zee, K. J., Vermorken, J. B., Viale, G., Voogd, A. C., Wapnir, I. L., White, J. R., Smidt, M. L. 2014; 106 (12)

View details for DOI 10.4300/JGME-D-14-00086.1

View details for PubMedID 24949168

Indocyanine Green and Fluorescence Lymphangiography for Sentinel Lymph Node Identification in Cutaneous Melanoma JOURNAL OF SURGICAL ONCOLOGY Cloyd, J. M., Wapnir, I. L., Read, B. M., Swetter, S., Greco, R. S. 2014; 110 (7): 888-892
PREDICT: Instituting an Educational Time Out in the Operating Room. Journal of graduate medical education Yang, R. L., Esquivel, M., Erdrich, J., Lau, J., Melcher, M. L., Wapnir, I. L. 2014; 6 (2): 382-383
Descriptive Findings on the Utility of Indocyanine Green and Isosulfan Blue in the Mapping of Arm-Draining Lymphatics and Nodes Wapnir, I. L., Ahmed, S. M., Choy, N. S., Porter, C., Meyer, S. SPRINGER. 2014: 121

Abstract

The limited entry of anticancer drugs into the central nervous system represents a special therapeutic challenge for patients with brain metastases and is primarily due to the blood brain barrier (BBB). Albumin-bound Evans blue (EB) dye is too large to cross the BBB but can grossly stain tissue blue when the BBB is disrupted. The course of tumor development and the integrity of the BBB were studied in three preclinical breast cancer brain metastasis (BCBM) models. A luciferase-transduced braintropic clone of MDA-231 cell line was used. Nude mice were subjected to stereotactic intracerebral inoculation, mammary fat pad-derived tumor fragment implantation, or carotid artery injections. EB was injected 30 min prior to euthanasia at various timepoints for each of the BCBM model animals. Serial bioluminescent imaging demonstrated exponential tumor growth in all models. Carotid BCBM appeared as diffuse multifocal cell clusters. EB aided the localization of metastases ex vivo. Tumor implants stained blue at 7 days whereas gross staining was not evident until day 14 in the stereotactic model and day 28 for the carotid model. EB assessment of the integrity of the BBB provides useful information relevant to drug testing in preclinical BCBM models.

View details for DOI 10.1007/s10549-014-2854-5

View details for PubMedID 24510011

Initial Results With Black Ink Tattooing of Biopsied Axillary Lymph Nodes Choy, N. S., Lipson, J., Kieryn, A., Porter, C., Ikeda, D., Pal, S., Trinh, L., Ozawa, M., Allison, K., Jensen, K., Wapnir, I. SPRINGER. 2014: 3536
Ex vivo Evans blue assessment of the blood brain barrier in three breast cancer brain metastasis models. Breast cancer research and treatment Do, J., Foster, D., Renier, C., Vogel, H., Rosenblum, S., Doyle, T. C., Tse, V., Wapnir, I. 2014; 144 (1): 93-101

Abstract

Patients with isolated locoregional recurrences (ILRR) of breast cancer have a high risk of distant metastasis and death from breast cancer. We aimed to establish whether adjuvant chemotherapy improves the outcome of such patients.The CALOR trial was a pragmatic, open-label, randomised trial that accrued patients with histologically proven and completely excised ILRR after unilateral breast cancer who had undergone a mastectomy or lumpectomy with clear surgical margins. Eligible patients were enrolled from hospitals worldwide and were centrally randomised (1:1) to chemotherapy (type selected by the investigator; multidrug for at least four courses recommended) or no chemotherapy, using permuted blocks, and stratified by previous chemotherapy, oestrogen-receptor and progesterone-receptor status, and location of ILRR. Patients with oestrogen-receptor-positive ILRR received adjuvant endocrine therapy, radiation therapy was mandated for patients with microscopically involved surgical margins, and anti-HER2 therapy was optional. The primary endpoint was disease-free survival. All analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00074152.From Aug 22, 2003, to Jan 31, 2010, 85 patients were randomly assigned to receive chemotherapy and 77 were assigned to no chemotherapy. At a median follow-up of 49 years (IQR 36-6 0), 24 (28%) patients had disease-free survival events in the chemotherapy group compared with 34 (44%) in the no chemotherapy group. 5-year disease-free survival was 69% (95% CI 56-79) with chemotherapy versus 57% (44-67) without chemotherapy (hazard ratio 059 [95% CI 035-099]; p=0046). Adjuvant chemotherapy was significantly more effective for women with oestrogen-receptor-negative ILRR (pinteraction=0046), but analyses of disease-free survival according to the oestrogen-receptor status of the primary tumour were not statistically significant (pinteraction=043). Of the 81 patients who received chemotherapy, 12 (15%) had serious adverse events. The most common adverse events were neutropenia, febrile neutropenia, and intestinal infection.Adjuvant chemotherapy should be recommended for patients with completely resected ILRR of breast cancer, especially if the recurrence is oestrogen-receptor negative.US Department of Health and Human Services, Swiss Group for Clinical Cancer Research (SAKK), Frontier Science and Technology Research Foundation, Australian and New Zealand Breast Cancer Trials Group, Swedish Cancer Society, Oncosuisse, Cancer Association of South Africa, Foundation for Clinical Research of Eastern Switzerland (OSKK), Grupo Espaol de Investigacin en Cncer de Mama (GEICAM), and the Dutch Breast Cancer Trialists' Group (BOOG).

View details for DOI 10.1016/S1470-2045(13)70589-8

View details for PubMedID 24439313

Indocyanine Green and Fluorescence Lymphangiography for Sentinel Lymph Node Identification in Melanoma Cloyd, J. M., Wapnir, I. L., Read, B. M., Greco, R. S. SPRINGER. 2014: S121

Abstract

Nipple-sparing mastectomies (NSM) have gained acceptance in the field of breast oncology. Ischemic complications involving the nipple-areolar complex (NAC) occur in 3-37 % of cases. Skin perfusion can be monitored intraoperatively using indocyanine green (IC-GREEN, ICG) and a specialized infrared camera-computer system (SPY Elite). The blood flow pattern to the breast skin and the NAC were evaluated and a classification scheme was developed.Preincision baseline and postmastectomy skin perfusion studies were performed intraoperatively using 3 mL of ICG. The pattern of arterial blood inflow was classified according to whether perfusion appeared to originate predominantly from the underlying breast tissue (V1), the surrounding skin (V2), or a combination of V1 and V2 (V3). Ischemia, resection, or delayed complications of NAC were recorded.Thirty-nine breasts were interrogated. Seven (18 %) demonstrated a V1 pattern, 18 (46 %) a V2 pattern, and 14 (36 %) a V3 pattern. Seven (18 %) NACs were removed; six intraoperatively and the seventh in a delayed fashion. Notably, five of the seven resected NACs had a V1 pattern. Overall, 71 % of all V1 cases demonstrated profound ischemic changes by intraoperative clinical judgment and SPY imaging. The rates of resection of the NAC differed significantly between perfusion patterns (Fisher's exact test, p = 0.0003).Three perfusion patterns for the NAC are defined. The V1 pattern had the highest rate of NAC ischemia in NSM. Imaging NAC and skin perfusion during NSMs is a useful adjunctive tool with potential to direct placement of mastectomy incisions and minimize ischemic complications.

View details for DOI 10.1245/s10434-013-3214-0

View details for PubMedID 24046104

Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR): a randomised trial LANCET ONCOLOGY Aebi, S., Gelber, S., Anderson, S. J., Lang, I., Robidoux, A., Martin, M., Nortier, J. W., Paterson, A. H., Rimawi, M. F., Canada, J. M., Thuerlimann, B., Murray, E., Mamounas, E. P., Geyer, C. E., Price, K. N., Coates, A. S., Gelber, R. D., Rastogi, P., Wolmark, N., Wapnir, I. L. 2014; 15 (2): 156-163

Abstract

Triple-negative breast cancer (TNBC) is aggressive and lacks targeted therapies. Phosphatidylinositide 3-kinase (PI3K) / mammalian target of rapamycin (mTOR) pathways are frequently activated in TNBC patient tumors at the genome, gene expression and protein levels, and mTOR inhibitors have been shown to inhibit growth in TNBC cell lines. We describe a panel of patient-derived xenografts representing multiple TNBC subtypes and use them to test preclinical drug efficacy of two mTOR inhibitors, sirolimus (rapamycin) and temsirolimus (CCI-779).We generated a panel of seven patient-derived orthotopic xenografts from six primary TNBC tumors and one metastasis. Patient tumors and corresponding xenografts were compared by histology, immunohistochemistry, array comparative genomic hybridization (aCGH) and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) sequencing; TNBC subtypes were determined. Using a previously published logistic regression approach, we generated a rapamycin response signature from Connectivity Map gene expression data and used it to predict rapamycin sensitivity in 1401 human breast cancers of different intrinsic subtypes, prompting in vivo testing of mTOR inhibitors and doxorubicin in our TNBC xenografts.Patient-derived xenografts recapitulated histology, biomarker expression and global genomic features of patient tumors. Two primary tumors had PIK3CA coding mutations, and 5/6 primary tumors showed flanking intron single nucleotide polymorphisms (SNPs) with conservation of sequence variations between primary tumors and xenografts, even on subsequent xenograft passages. Gene expression profiling showed that our models represent at least four of six TNBC subtypes. The rapamycin response signature predicted sensitivity for 94% of basal-like breast cancers in a large dataset. Drug testing of mTOR inhibitors in our xenografts showed 77 to 99% growth inhibition, significantly more than doxorubicin; protein phosphorylation studies indicated constitutive activation of the mTOR pathway that decreased with treatment. However, no tumor was completely eradicated.A panel of patient-derived xenograft models covering a spectrum of TNBC subtypes was generated that histologically and genomically matched original patient tumors. Consistent with in silico predictions, mTOR inhibitor testing in our TNBC xenografts showed significant tumor growth inhibition in all, suggesting that mTOR inhibitors can be effective in TNBC, but will require use with additional therapies, warranting investigation of optimal drug combinations.

View details for DOI 10.1186/bcr3640

View details for PubMedID 24708766

Intraoperative imaging of nipple perfusion patterns and ischemic complications in nipple-sparing mastectomies. Annals of surgical oncology Wapnir, I., Dua, M., Kieryn, A., Paro, J., Morrison, D., Kahn, D., Meyer, S., Gurtner, G. 2014; 21 (1): 100-106

View details for DOI 10.1186/bcr3640

View details for Web of Science ID 000338990900021

Patient-derived xenografts of triple-negative breast cancer reproduce molecular features of patient tumors and respond to mTOR inhibition. Breast cancer research Zhang, H., Cohen, A. L., Krishnakumar, S., Wapnir, I. L., Veeriah, S., Deng, G., Coram, M. A., Piskun, C. M., Longacre, T. A., Herrler, M., Frimannsson, D. O., Telli, M. L., Dirbas, F. M., Matin, A. C., Dairkee, S. H., Larijani, B., Glinsky, G. V., Bild, A. H., Jeffrey, S. S. 2014; 16 (2): R36-?
Patient-derived xenografts of triple-negative breast cancer reproduce molecular features of patient tumors and respond to mTOR inhibition BREAST CANCER RESEARCH Zhang, H., Cohen, A. L., Krishnakumar, S., Wapnir, I. L., Veeriah, S., Deng, G., Coram, M. A., Piskun, C. M., Longacre, T. A., Herrler, M., Frimannsson, D. O., Telli, M. L., Dirbas, F. M., Matin, A. C., Dairkee, S. H., Larijani, B., Glinsky, G. V., Bild, A. H., Jeffrey, S. S. 2014; 16 (2)
FIVE YEAR SAFETY AND FERTILITY OUTCOMES IN WOMEN WHO UNDERWENT OVARIAN STIMULATION FOR FERTILITY PRESERVATION PRIOR TO CHEMOTHERAPY FOR INVASIVE BREAST CANCER. Kort, J. D., Wapnir, I., Seiger, K., Westphal, L. ELSEVIER SCIENCE INC. 2013: S116S117

Abstract

Although mastectomy is considered the gold standard for male breast cancer (MBC), the utilization of lumpectomy and its impact on outcomes in MBC patients has not been previously studied.The Surveillance, Epidemiology and End Results (SEER) database was used to identify all MBC patients who underwent either mastectomy or less than mastectomy (i.e., lumpectomy) between 1983 and 2009.A total of 4707 (86.8 %) men underwent mastectomy and 718 (13.2 %) underwent lumpectomy. A greater proportion of patients underwent lumpectomy later in the study period (1983 to 1986, 10.6 %, vs. 2007 to 2009, 15.1 %). A greater percentage of lumpectomy patients were 80 years or older (21.3 % vs. 16.3 %), had stage IV disease (7.3 % vs. 3.1 %), and received no lymph node sampling (34.3 % vs. 6.9 %). Only 35.4 % of patients underwent adjuvant radiotherapy after lumpectomy. Ten-year breast cancer-specific survival and overall survival were 82.8 % and 46.9 %, respectively, in lumpectomy patients vs. 77.3 % and 46.4 %, respectively, in mastectomy patients. On Cox proportional hazards regression, lumpectomy was not independently associated with worse breast cancer-specific survival (odds ratio 1.09, 95 % confidence interval 0.87-1.37) or overall survival (odds ratio 1.12, 95 % confidence interval 0.98-1.27) after controlling for age, race, stage, and grade, as well as whether radiotherapy was received.Lumpectomy is performed in a small but growing proportion of MBC patients. These patients are not only older and more likely to have advanced disease at the time of diagnosis, but they also are less likely to receive standard of care therapy, such as lymph node sampling and adjuvant radiotherapy. Despite these observations, breast cancer-specific survival is unaffected by the type of surgery.

View details for DOI 10.1245/s10434-013-2918-5

View details for PubMedID 23460016

PrECOG 0105: Final efficacy results from a phase II study of gemcitabine (G) and carboplatin (C) plus iniparib (BSI-201) as neoadjuvant therapy for triple-negative (TN) and BRCA1/2 mutation-associated breast cancer Telli, M. L., Jensen, K. C., Kurian, A. W., Vinayak, S., Lipson, J. A., Schackmann, E. A., Wapnir, I., Carlson, R. W., Sparano, J. A., Head, B., Goldstein, L. J., Haley, B. B., Dakhil, S. R., Manola, J., Ford, J. M. AMER SOC CLINICAL ONCOLOGY. 2013

Abstract

Lumpectomy is performed in a small but growing proportion of men with breast cancer. It is unknown whether men undergoing breast-conserving surgery (BCS) receive care compliant with breast cancer treatment guidelines. Patients with breast cancer in the surveillance, epidemiology, and end results (SEER) database who underwent lumpectomy between 1983 and 2009 were identified. Gender differences in the receipt of lymph node staging and adjuvant radiation therapy were assessed. Multivariate logistic regression was utilized to evaluate the independent association of gender on these outcomes. The influence of gender on breast cancer-specific survival (BCSS) was analyzed. 382,030 of 824,408 (46.3%) women compared to 712 of 6,039 (11.8%) men with breast cancer underwent lumpectomy. Men were older, more likely to be black, less likely to have stage I disease and more likely to have stage IV disease. Only 59.2% of men had lymph nodes sampled at the time of surgery compared to 81.6% of women (p<0.0001). In addition, only 35.4% of men received adjuvant breast radiation therapy compared to 69.8% of women (p<0.0001). After controlling for age, race, stage, grade, and year of diagnosis, female gender was significantly associated with receiving adjuvant radiation therapy (OR 2.9, 95% CI 2.4-3.4) and lymph node staging (OR 1.6, 95% CI 1.3-1.90). Five- and ten-year BCSS were 88.0 and 83.5% for men compared to 93.2 and 88.2% for women (p<0.001). Men with breast cancer are less likely to receive lymph node staging or adjuvant radiation therapy following BCS compared to women.

View details for DOI 10.1007/s10549-013-2517-y

View details for PubMedID 23572298

Outcomes of Partial Mastectomy in Male Breast Cancer Patients: Analysis of SEER, 1983-2009 ANNALS OF SURGICAL ONCOLOGY Cloyd, J. M., Hernandez-Boussard, T., Wapnir, I. L. 2013; 20 (5): 1545-1550
Poor compliance with breast cancer treatment guidelines in men undergoing breast-conserving surgery. Breast cancer research and treatment Cloyd, J. M., Hernandez-Boussard, T., Wapnir, I. L. 2013; 139 (1): 177-182
The Fate of DCIS After Neoadjuvant Treatment for Invasive Breast Cancer 14th Annual Meeting of the American-Society-of-Breast-Surgeons Porter, C., Morrison, D., Wapnir, I. SPRINGER. 2013: 9495

Abstract

Papilloma is the most common finding associated with pathologic nipple discharge. In the absence of breast imaging abnormalities, the incidence of occult malignancy is <3%.To determine the predictive value of nipple discharge cytology in conjunction with breast imaging.Retrospective review of 160 charts; inclusion criteria of clinically pathologic nipple discharge, subsequent excisional biopsy, and absence of palpable abnormalities. Nipple discharge cytology categorized as negative, atypical, suspicious, and papillary. Breast imaging was analyzed. Preoperative tests were correlated to final surgical pathology.89 patients identified. Sixty-five had positive cytology, with a false positive rate of 32.3%. They were associated with papillomas in 52%, benign non-papillary in 33% and malignant lesions in 9% of cases. Nipple discharge cytology was positive in 69.6% of papillomas and 92% of atypical/malignant lesions; 30% had abnormal breast imaging and positive cytology. Nipple discharge cytology had a sensitivity of 74.5%, specificity of 30%, and positive predictive value of 68%. The positive predictive value increased to 85% with associated abnormal breast imaging.Nipple discharge cytology is useful in evaluating pathologic discharge. However, negative cytology with negative imaging is not enough to avoid surgery in cases of suspicious clinical presentation.

View details for DOI 10.1002/jso.23091

View details for PubMedID 22396104

Increasing Use of Lumpectomy in Men with Breast Cancer: Outcomes Analysis of SEER Data 1983-2009 Cloyd, J. M., Wapnir, I. L. SPRINGER. 2013: S50

View details for DOI 10.1111/j.1524-4741.2012.01255.x

View details for PubMedID 22716922

The diagnostic value of nipple discharge cytology: Breast imaging complements predictive value of nipple discharge cytology JOURNAL OF SURGICAL ONCOLOGY Kalu, O. N., Chow, C., Wheeler, A., Kong, C., Wapnir, I. 2012; 106 (4): 381-385
MRI Enhancement Correlates With High Grade Desmoid Tumor of Breast BREAST JOURNAL Kim, M. J., Wapnir, I. L., Ikeda, D. M., Chisholm, K. M., Do, Y., Daniel, B. L. 2012; 18 (4): 374-376

Abstract

Young women diagnosed with breast cancer typically face systemic treatments that may delay childbearing or permanently impair their fertility. These concerns add to the stress experienced by young cancer survivors. Timely counseling and providing fertility preservation through cryopreservation of eggs or embryos have become an important quality of life issue. We analyzed the impact of fertility preservation procedures on the initiation of treatment for breast cancer and discuss critical aspects of the process.

View details for DOI 10.1016/j.ygyno.2011.11.028

View details for PubMedID 22173210

Evaluation of the Oncotype Dx recurrence score (RS) in hormone-positive ipsilateral breast tumor recurrences Wapnir, I., Florero, M. AMER SOC CLINICAL ONCOLOGY. 2012
Integration and safety of fertility preservation in a breast cancer program GYNECOLOGIC ONCOLOGY Westphal, L. M., Wapnir, I. L. 2012; 124 (3): 474-476
Determining Adequate Nipple Areolar Complex Perfusion in Breast Cancer Related Mastectomies 65th Annual Cancer Symposium of the Society-of-Surgical-Oncology (SSO) Kieryn, A., Dua, M., Paro, J., Meyer, S., Gurtner, G., Wapnir, I. SPRINGER. 2012: S91S91

Abstract

Ipsilateral breast tumor recurrence (IBTR) is the most common failure event after lumpectomy for ductal carcinoma in situ (DCIS). We evaluated invasive IBTR (I-IBTR) and its influence on survival among participants in two National Surgical Adjuvant Breast and Bowel Project (NSABP) randomized trials for DCIS.In the NSABP B-17 trial (accrual period: October 1, 1985, to December 31, 1990), patients with localized DCIS were randomly assigned to the lumpectomy only (LO, n = 403) group or to the lumpectomy followed by radiotherapy (LRT, n = 410) group. In the NSABP B-24 double-blinded, placebo-controlled trial (accrual period: May 9, 1991, to April 13, 1994), all accrued patients were randomly assigned to LRT+ placebo, (n=900) or LRT + tamoxifen (LRT + TAM, n = 899). Endpoints included I-IBTR, DCIS-IBTR, contralateral breast cancers (CBC), overall and breast cancer-specific survival, and survival after I-IBTR. Median follow-up was 207 months for the B-17 trial (N = 813 patients) and 163 months for the B-24 trial (N = 1799 patients).Of 490 IBTR events, 263 (53.7%) were invasive. Radiation reduced I-IBTR by 52% in the LRT group compared with LO (B-17, hazard ratio [HR] of risk of I-IBTR = 0.48, 95% confidence interval [CI] = 0.33 to 0.69, P < .001). LRT + TAM reduced I-IBTR by 32% compared with LRT + placebo (B-24, HR of risk of I-IBTR = 0.68, 95% CI = 0.49 to 0.95, P = .025). The 15-year cumulative incidence of I-IBTR was 19.4% for LO, 8.9% for LRT (B-17), 10.0% for LRT + placebo (B-24), and 8.5% for LRT + TAM. The 15-year cumulative incidence of all contralateral breast cancers was 10.3% for LO, 10.2% for LRT (B-17), 10.8% for LRT + placebo (B-24), and 7.3% for LRT + TAM. I-IBTR was associated with increased mortality risk (HR of death = 1.75, 95% CI = 1.45 to 2.96, P < .001), whereas recurrence of DCIS was not. Twenty-two of 39 deaths after I-IBTR were attributed to breast cancer. Among all patients (with or without I-IBTR), the 15-year cumulative incidence of breast cancer death was 3.1% for LO, 4.7% for LRT (B-17), 2.7% for LRT + placebo (B-24), and 2.3% for LRT + TAM.Although I-IBTR increased the risk for breast cancer-related death, radiation therapy and tamoxifen reduced I-IBTR, and long-term prognosis remained excellent after breast-conserving surgery for DCIS.

View details for DOI 10.1093/jnci/djr027

View details for PubMedID 21398619

A Phase II Study of Gemcitabine and Carboplatin (GC) Plus Iniparib (BSI-201) as Neoadjuvant Therapy for Triple-Negative and BRCA1/2 Mutation-Associated Breast Cancer. Telli, M. L., Kurian, A. W., Jensen, K. C., Vinayak, S., Flaherty, P., Lipson, J. A., Wapnir, I., Daniel, B., Carlson, R. W., Mills, M. A., Chang, P., Schackmann, E., Rocha, C., Sherman, B., Blackwood-Chirchir, A., Bradley, C., Ford, J. M. AMER ASSOC CANCER RESEARCH. 2011

Abstract

Na(+)/I(-) symporter (NIS)-mediated iodide uptake into thyroid follicular cells serves as the basis of radioiodine therapy for thyroid cancer. NIS protein is also expressed in the majority of breast tumors, raising potential for radionuclide therapy of breast cancer. KT5823, a staurosporine-related protein kinase inhibitor, has been shown to increase thyroid-stimulating hormone-induced NIS expression, and thus iodide uptake, in thyroid cells. In this study, we found that KT5823 does not increase but decreases iodide uptake within 0.5 h of treatment in trans-retinoic acid and hydrocortisone-treated MCF-7 breast cancer cells. Moreover, KT5823 accumulates hypoglycosylated NIS, and this effect is much more evident in breast cancer cells than thyroid cells. The hypoglycosylated NIS is core glycosylated, has not been processed through the Golgi apparatus, but is capable of trafficking to the cell surface. KT5823 impedes complex NIS glycosylation at a regulatory point similar to brefeldin A along the N-linked glycosylation pathway, rather than targeting a specific N-glycosylated site of NIS. KT5823-mediated effects on NIS activity and glycosylation are also observed in other breast cancer cells as well as human embryonic kidney cells expressing exogenous NIS. Taken together, KT5823 will serve as a valuable pharmacological reagent to uncover mechanisms underlying differential NIS regulation between thyroid and breast cancer cells at multiple levels.

View details for DOI 10.1210/en.2010-0782

View details for Web of Science ID 000287520900006

View details for PubMedID 21209020

View details for PubMedCentralID PMC3040054

Long-Term Outcomes of Invasive Ipsilateral Breast Tumor Recurrences After Lumpectomy in NSABP B-17 and B-24 Randomized Clinical Trials for DCIS JOURNAL OF THE NATIONAL CANCER INSTITUTE Wapnir, I. L., Dignam, J. J., Fisher, B., Mamounas, E. P., Anderson, S. J., Julian, T. B., Land, S. R., Margolese, R. G., Swain, S. M., Costantino, J. P., Wolmark, N. 2011; 103 (6): 478-488

Abstract

Eusorbents are considered the exogenous substances that facilitate and enhance intestinal absorption. Eusorption is the process by which eusorbents affect the mechanisms of intestinal absorption. These 2 concepts should be distinguished from the well-known probiotics and prebiotics that may also play a role in benefiting the host. This review covers the eusorption paradigm in the optimization of oral rehydration and the treatment of diarrhea. The various factors that influence the validity of eusorbents to facilitate the eusorption were considered (i.e., viscosity, hydrating agents, and minerals such as zinc). The role of surface tension in solute absorption was addressed. The possible effects that eusorbents could play in the gene activation of the intestinal mucosa were also considered. This review should contribute to the understanding of absorptive enhancements of specific substances and their properties that facilitate the desired effects in health and disease.

View details for Web of Science ID 000292663900001

View details for PubMedID 21697533

KT5823 Differentially Modulates Sodium Iodide Symporter Expression, Activity, and Glycosylation between Thyroid and Breast Cancer Cells ENDOCRINOLOGY Beyer, S., Lakshmanan, A., Liu, Y., Zhang, X., Wapnir, I., Smolenski, A., Jhiang, S. 2011; 152 (3): 782-792
Eusorbents and Eusorption: A Review of Physiological Events to Therapeutic Concepts JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION Wapnir, R. A., Wapnir, I., Lifshitz, F. 2011; 30 (1): 1-10

Abstract

Combining tumor antigens with an immunostimulant can induce the immune system to specifically eliminate cancer cells. Generally, this combination is accomplished in an ex vivo, customized manner. In a preclinical lymphoma model, intratumoral injection of a Toll-like receptor 9 (TLR9) agonist induced systemic antitumor immunity and cured large, disseminated tumors.We treated 15 patients with low-grade B-cell lymphoma using low-dose radiotherapy to a single tumor site and-at that same site-injected the C-G enriched, synthetic oligodeoxynucleotide (also referred to as CpG) TLR9 agonist PF-3512676. Clinical responses were assessed at distant, untreated tumor sites. Immune responses were evaluated by measuring T-cell activation after in vitro restimulation with autologous tumor cells.This in situ vaccination maneuver was well-tolerated with only grade 1 to 2 local or systemic reactions and no treatment-limiting adverse events. One patient had a complete clinical response, three others had partial responses, and two patients had stable but continually regressing disease for periods significantly longer than that achieved with prior therapies. Vaccination induced tumor-reactive memory CD8 T cells. Some patients' tumors were able to induce a suppressive, regulatory phenotype in autologous T cells in vitro; these patients tended to have a shorter time to disease progression. One clinically responding patient received a second course of vaccination after relapse resulting in a second, more rapid clinical response.In situ tumor vaccination with a TLR9 agonist induces systemic antilymphoma clinical responses. This maneuver is clinically feasible and does not require the production of a customized vaccine product.

View details for DOI 10.1200/JCO.2010.28.9793

View details for Web of Science ID 000282272700032

View details for PubMedID 20697067

View details for PubMedCentralID PMC2954133

High Percentage of Triple Negative Tumors Present as Palpable Masses Kalu, O. N., Kurian, A., Wapnir, I. AMER ASSOC CANCER RESEARCH. 2010
In Situ Vaccination With a TLR9 Agonist Induces Systemic Lymphoma Regression: A Phase I/II Study JOURNAL OF CLINICAL ONCOLOGY Brody, J. D., Ai, W. Z., Czerwinski, D. K., Torchia, J. A., Levy, M., Advani, R. H., Kim, Y. H., Hoppe, R. T., Knox, S. J., Shin, L. K., Wapnir, I., Tibshirani, R. J., Levy, R. 2010; 28 (28): 4324-4332

Abstract

Breast cancer brain metastases are on the rise and their treatment is hampered by the limited entry and efficacy of anticancer drugs in this sanctuary. The sodium iodide symporter, NIS, actively transports iodide across the plasma membrane and is exploited clinically to deliver radioactive iodide into cells. As in thyroid cancers, NIS is expressed in many breast cancers including primary and metastatic tumors. In this study NIS expression was analyzed for the first time in 28 cases of breast cancer brain metastases using a polyclonal anti-NIS antibody directed against the terminal C-peptide of human NIS gene and immunohistochemical methods. Twenty-five tumors (84%) in this retrospective series were estrogen/progesterone receptor-negative and 15 (53.6%) were HER2+. Overall 21 (75%) cases and 80% of HER2 positive metastases were NIS positive. While the predominant pattern of NIS immunoreactivity is intracellular, plasma membrane immunopositivity was detected at least focally in 23.8% of NIS-positive samples. Altogether, these findings indicate that NIS expression is prevalent in breast cancer brain metastases and could have a therapeutic role via the delivery of radioactive iodide and selective ablation of tumor cells.

View details for DOI 10.1007/s11060-009-9971-8

View details for PubMedID 19618116

The Diagnostic Reliability of Nipple Discharge Cytology Kalu, O., Chow, C., Wheeler, A., Kong, C., Wapnir, I. SPRINGER. 2010: S176

Abstract

Protecting future childbearing motivates young women with breast cancer to seek oocyte or embryo cryopreservation. Concerns about delays in cancer treatment may influence patients and practitioners considering these procedures. In this study, we compared timing of chemotherapy in women who underwent ovarian stimulation/oocyte retrieval (OR) and embryo cryopreservation with those who did not.Eighty-two women younger than 40 years of age, who received adjuvant chemotherapy for breast cancer, were retrospectively identified. Nineteen underwent OR and 63 did not (CON). The timing of OR, surgery, and chemotherapy were compared with the time intervals between diagnosis and treatments in the CON group.The mean ages of women were 33.7 years (OR group) and 35.2 years (CON group); 84.2% of OR and 25.4% of CON were nulliparous. The median time from initial diagnosis to reproductive endocrinology consultation was 30.1 days (range 4 to 133 days) and from referral to OR was 32 days (range 13 to 66 days). The median times from initial diagnosis to chemotherapy in OR versus CON groups were 71 days (range 45 to 161 days) and 67 days (range 27 to 144 days), respectively, p < 0.27. The median time interval from definitive operation to chemotherapy was similar in the two groups: 30 days (OR; range 14 to 100 days) and 29 days (CON; range 12 to 120 days), p < 0.79.Fertility preservation is an important component of quality of life for young women with breast cancer. The time investment required for OR and cryopreservation is manageable and does not significantly prolong the time interval from diagnosis to start of adjuvant chemotherapy.

View details for DOI 10.1016/j.jamcollsurg.2009.08.006

View details for PubMedID 19854400

Breast cancer brain metastases express the sodium iodide symporter JOURNAL OF NEURO-ONCOLOGY Renier, C., Vogel, H., Offor, O., Yao, C., Wapnir, I. 2010; 96 (3): 331-336

Abstract

Locoregional failure (LRF) after breast-conserving therapy (BCT) is associated with increased risk of distant disease and death. The magnitude of this risk has not been adequately characterized in patients with lymph node-negative disease.Our study population included 3,799 women randomly assigned to five National Surgical Adjuvant Breast and Bowel Project protocols of node-negative disease (ie, B-13, B-14, B-19, B-20, and B-23) who underwent lumpectomy and whole breast irradiation with or without adjuvant systemic therapy. Cumulative incidences of ipsilateral breast tumor recurrence (IBTR) and other locoregional recurrence (oLRR) were calculated, along with distant-disease-free interval (DDFI) and overall survival (OS) after these events. Cox models were employed to model mortality by using clinical and pathologic factors jointly with these events.Four hundred nineteen patients (11.0%) experienced LRF: 342 (9.0%) experienced IBTR, and 77 (2.0%) experienced oLRR. The 12-year cumulative incidences of IBTR and oLRR in patients treated with adjuvant systemic therapy were 6.6% and 1.8%, respectively. Overall, 37.1% of IBTRs and 72.7% of oLRRs occurred within 5 years of diagnosis. Older age, black race, higher body mass index (BMI), larger tumors, and occurrence of IBTR or oLRR were significantly associated with increased mortality. The 5-year OS after IBTR and oLRR were 76.6% and 34.9%, respectively. Adjusted hazard ratios for mortality associated with IBTR and oLRR were significantly higher in estrogen receptor (ER)-negative patients than in ER-positive patients (P = .002 and P < .0001, respectively). Patients with early LRF had worse OS and DDFI than those with later-occurring LRF.Although LRF is uncommon in patients with node-negative breast cancer who are treated with lumpectomy, radiation, and adjuvant systemic therapy, those who do develop LRF have substantially worse OS and DDFI.

View details for DOI 10.1200/JCO.2008.19.8424

View details for Web of Science ID 000266195400011

View details for PubMedID 19349544

View details for PubMedCentralID PMC2684852

Timing of Breast Cancer Treatments with Oocyte Retrieval and Embryo Cryopreservation JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Baynosa, J., Westphal, L. M., Madrigrano, A., Wapnir, I. 2009; 209 (5): 603-607

Abstract

The metabolism of oxygen, although central to life, produces reactive oxygen species (ROS) that have been implicated in processes as diverse as cancer, cardiovascular disease and ageing. It has recently been shown that central nervous system stem cells and haematopoietic stem cells and early progenitors contain lower levels of ROS than their more mature progeny, and that these differences are critical for maintaining stem cell function. We proposed that epithelial tissue stem cells and their cancer stem cell (CSC) counterparts may also share this property. Here we show that normal mammary epithelial stem cells contain lower concentrations of ROS than their more mature progeny cells. Notably, subsets of CSCs in some human and murine breast tumours contain lower ROS levels than corresponding non-tumorigenic cells (NTCs). Consistent with ROS being critical mediators of ionizing-radiation-induced cell killing, CSCs in these tumours develop less DNA damage and are preferentially spared after irradiation compared to NTCs. Lower ROS levels in CSCs are associated with increased expression of free radical scavenging systems. Pharmacological depletion of ROS scavengers in CSCs markedly decreases their clonogenicity and results in radiosensitization. These results indicate that, similar to normal tissue stem cells, subsets of CSCs in some tumours contain lower ROS levels and enhanced ROS defences compared to their non-tumorigenic progeny, which may contribute to tumour radioresistance.

View details for DOI 10.1038/nature07733

View details for PubMedID 19194462

Prognosis After Ipsilateral Breast Tumor Recurrence and Locoregional Recurrences in Patients Treated by Breast-Conserving Therapy in Five National Surgical Adjuvant Breast and Bowel Project Protocols of Node-Negative Breast Cancer 41st Annual Meeting of the American-Society-of-Clinical-Oncology Anderson, S. J., Wapnir, I., Dignam, J. J., Fisher, B., Mamounas, E. P., Jeong, J., Geyer, C. E., Wickerham, D. L., Costantino, J. P., Wolmark, N. AMER SOC CLINICAL ONCOLOGY. 2009: 246673

Abstract

The sodium iodide symporter (NIS) mediates iodide transport into cells and has been identified in approximately 70% of breast cancers. Functional NIS expression raises the possibility of using (131)I for therapeutic targeting of tumor cells. Treatment of triple-negative breast cancers [estrogen/progesterone receptor-negative and HER2-negative (ER-/PR-/HER2-)] is primarily limited to chemotherapy. Our aim was to characterize NIS expression in this subset of tumors.Archival tissue sections from 23 women with triple-negative breast cancer were analyzed for NIS expression using immunohistochemical methods and an anti-human NIS antibody. Tumors were evaluated for the presence of plasma membrane immunoreactivity. One patient with a NIS-expressing positive tumor underwent (123)I scintigraphic imaging with dosimetric analysis.Fifteen cases (65.2%) demonstrated NIS-positivity with 11 tumors (47.8%) exhibiting strong expression. Plasma membrane immunoreactivity was observed in four breast cancers and was equivocal in another four tumors. Tumor-specific radioiodide uptake was demonstrated by (123)I scintigraphy in a patient with a large primary breast cancer unresponsive to neoadjuvant therapy. The tumor concentrated 2.05, 1.53, and 1.96 times more isotope than normal breast tissue at 1, 5, and 21 h. The relative increased uptake is consistent with positive NIS expression in the tumor on definitive surgery; however, the cumulative concentration in the tumor was not sufficient to achieve a therapeutic effect, had the isotope been (131)I.NIS is strongly expressed in a significant proportion of triple-negative breast cancer cells, suggesting a potential role for NIS-directed (131)I-radioablative strategies in this patient population.

View details for DOI 10.1245/s10434-008-0280-9

View details for PubMedID 19184238

Association of reactive oxygen species levels and radioresistance in cancer stem cells NATURE Diehn, M., Cho, R. W., Lobo, N. A., Kalisky, T., Dorie, M. J., Kulp, A. N., Qian, D., Lam, J. S., Ailles, L. E., Wong, M., Joshua, B., Kaplan, M. J., Wapnir, I., Dirbas, F. M., Somlo, G., Garberoglio, C., Paz, B., Shen, J., Lau, S. K., Quake, S. R., Brown, J. M., Weissman, I. L., Clarke, M. F. 2009; 458 (7239): 780-U123
Endogenous NIS Expression in Triple-Negative Breast Cancers ANNALS OF SURGICAL ONCOLOGY Renier, C., Yao, C., Goris, M., Ghosh, M., Katznelson, L., Nowles, K., Gambhir, S. S., Wapnir, I. 2009; 16 (4): 962-968

Abstract

The utility of chemotherapy for women who experience a locoregional recurrence after primary treatment of early breast cancer remains an open question. An international collaborative trial is being conducted by the Breast International Group (BIG), the International Breast Cancer Study Group (IBCSG), and the National Surgical Adjuvant Breast and Bowel Project (NSABP) to determine the effectiveness of cytotoxic therapy for these patients, either alone or in addition to selective use of hormonal therapy and trastuzumab.The trial population includes women who have had a previous diagnosis of invasive breast cancer treated by mastectomy or breast-conserving surgery, but subsequently develop an isolated local and/or regional ipsilateral invasive recurrence. Excision of all macroscopic tumor without evidence of systemic disease is required for study entry. Patients are randomized to receive chemotherapy or no chemotherapy; type of chemotherapy is not protocol-specified. Radiation, hormonal therapy, and trastuzumab are given as appropriate. The primary endpoint is disease-free survival (DFS). Quality-of-life measurements are collected at baseline, and then at 9 and 12 months. The accrual goal is 977 patients.This report describes the characteristics of the first 99 patients. Sites of recurrence at study entry were: breast (56%), mastectomy scar/chest wall (35%), and regional lymph nodes (9%). Two-thirds of patients have estrogen-receptor-positive recurrences.This is the only trial actively investigating the question of "adjuvant" chemotherapy in locally recurrent breast cancer. The case mix of accrual to date indicates a broad representation of this patient population.

View details for DOI 10.1245/s10434-008-0129-2

View details for Web of Science ID 000260509400033

View details for PubMedID 18784962

View details for PubMedCentralID PMC2576492

Development of a breast cancer brain metastases model to study I-131 radioablative therapy. 31st Annual Meeting of the San Antonio Breast Cancer Symposium Renier, C., De, A., Hou, L., Dunkel, J., Sun, A., Prugpichailers, T., Gambhir, S. S., Tse, V., Wapnir, I. L. AMER ASSOC CANCER RESEARCH. 2009: 159S160S

Abstract

In this phase III, multinational, randomized trial, the International Breast Cancer Study Group, Breast International Group, and the National Surgical Adjuvant Breast and Bowel Project will attempt to define the effectiveness of cytotoxic therapy for patients with locoregional recurrence of breast cancer. We will evaluate whether chemotherapy prolongs disease-free survival and, secondarily, whether its use improves overall survival and systemic disease-free survival. Quality of life measurements will be monitored during the first 12 months of the study. Women who have had a previous diagnosis of invasive breast cancer treated by mastectomy or breast-conserving surgery and who have undergone complete surgical excision of all macroscopic disease but who subsequently develop isolated local and/or regional ipsilateral invasive recurrence are eligible. Patients are randomized to observation/no adjuvant chemotherapy or to adjuvant chemotherapy; all suitable patients receive radiation, hormonal, and trastuzumab therapy. Radiation therapy is recommended for patients who have not received previous adjuvant radiation therapy but is required for those with microscopically positive margins. The radiation field must encompass the tumor bed plus a surrounding margin to a dose of >or= 40 Gy. Radiation therapy will be administered before, during, or after chemotherapy. All women with estrogen receptor-positive and/or progesterone receptor-positive recurrence must receive hormonal therapy, with the agent and duration to be determined by the patient's investigator. Adjuvant trastuzumab therapy is permitted for those with HER2- positive tumors, provided that intent to treat is declared before randomization. Although multidrug regimens are preferred, the agents, doses, and use of supportive therapy are at the discretion of the investigator.

View details for DOI 10.3816/CBC.2008.n.035

View details for Web of Science ID 000256914800013

View details for PubMedID 18650162

Progress on BIG 1-02/IBCSG 27-02/NSABP B-37, a Prospective Randomized Trial Evaluating Chemotherapy after Local Therapy for Isolated Locoregional Recurrences of Breast Cancer ANNALS OF SURGICAL ONCOLOGY Wapnir, I. L., Aebi, S., Gelber, S., Anderson, S. J., Lang, I., Robidoux, A., Mamounas, E. P., Wolmark, N. 2008; 15 (11): 3227-3231
A randomized clinical trial of adjuvant chemotherapy for radically resected locoregional relapse of breast cancer: IBCSG 27-02, BIG 1-02, and NSABP B-37 CLINICAL BREAST CANCER Wapnir, I. L., Aebi, S., Geyer, C. E., Zahrieh, D., Gelber, R. D., Anderson, S. J., Robidoux, A., Bernhard, J., Maibach, R., Castiglione-Gertsch, M., Coates, A. S., Piccart, M. J., Clemons, M. J., Costantino, J. P., Wolmark, N. 2008; 8 (3): 287-292

Abstract

Metastases to the breast comprise 0.5%-2% of breast neoplasms. This is a case report of an 18-year-old woman with an alveolar soft part sarcoma metastatic to the breast.

View details for PubMedID 18501064

New models and online calculator for predicting non-sentinel lymph node status in sentinel lymph node positive breast cancer patients 30th Annual San Antonio Breast Cancer Symposium Kohrt, H., Olshen, R., Bermas, H., GOODSON, W., Henry, S., Rouse, R., Bailey, L., Philben, V., Dirbas, F., Dunn, J., Johnson, D., Wapnir, I., Carlson, R., STOCKDALE, F., Hansen, N., JEFFREY, S. SPRINGER. 2008: 58888
Metastases to the breast: Alveolar soft part sarcoma in adolescents CLINICAL BREAST CANCER Madrigrano, A., Beach, B., Wheeler, A., Wapnir, I. 2008; 8 (1): 92-93
Progress on BIG 1-02/IBCSG 27-02/NSABP B-37, a prospective randomized trial evaluating chemotherapy after local therapy for isolated locoregional recurrences Wapnir, I. L., Zahrieh, D., Aebi, S. SPRINGER. 2008: 9

Abstract

A 50 year old woman with a 10-year history of systemic lupus erythematosus (SLE) and intermittent low-dose cyclophosphamide therapy developed a palpable mass at the periphery of her left breast. Ultrasound guided core biopsy revealed a spindle cell neoplasm characterized on final pathology as a low grade leiomyosarcoma.

View details for DOI 10.1186/1757-1626-1-301

View details for PubMedID 18992149

View details for PubMedCentralID PMC2590612

Comparative analysis of time delays to initiation of chemotherapy in women undergoing oocyte retrieval with cryopreservation De la Pena, J. L., Madrigrano, A., Westphal, L., Wapnir, I. L. SPRINGER. 2008: 81

Abstract

Infertility is a concern to young women diagnosed with breast cancer. Advances in fertility technology have made it possible to bank fertilized embryos.Twenty-three women, ages 27 to 40 years, underwent stimulation/oocyte retrieval before the start of adjuvant therapies. Time intervals between retrieval and therapeutic procedures were analyzed.The average stimulation to egg retrieval was 11.5 days (range 9-20 d). The average time interval from first evaluation to oocyte retrieval was 33.3 days (range 10-65 d). Overall, the mean time from definitive surgery to initiation of chemotherapy was 46.8 days (n = 20). For 6 patients referred by surgeons, the mean time from fertility consult to retrieval was 48.8 days (range 16-118 d), and from definitive surgery to initiation of chemotherapy was 45 days (range 15-93 d).Egg retrieval cryopreservation can be integrated with breast cancer work-up and surgical procedures. Early referrals to a fertility specialist by surgeons will help patients' safeguard future childbearing.

View details for DOI 10.1016/j.amjsurg.2007.06.008

View details for PubMedID 17826059

Leiomyosarcoma of the breast in a patient with a 10-year-history of cyclophosphamide exposure: a case report. Cases journal De la Pena, J., Wapnir, I. 2008; 1 (1): 301-?
Egg retrieval with cryopreservation does not delay breast cancer treatment 8th Annual Meeting of the American-Society-of-Breast-Surgeons Madrigrano, A., Westphal, L., Wapnir, I. EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2007: 47781

Abstract

The sodium/iodide symporter (NIS) is a plasma membrane glycoprotein that mediates iodide (I-) transport in the thyroid, lactating breast, salivary glands, and stomach. Whereas NIS expression and regulation have been extensively investigated in healthy and neoplastic thyroid and breast tissues, little is known about NIS expression and function along the healthy and diseased gastrointestinal tract.Thus, we investigated NIS expression by immunohistochemical analysis in 155 gastrointestinal tissue samples and by immunoblot analysis in 17 gastric tumors from 83 patients.Regarding the healthy Gl tract, we observed NIS expression exclusively in the basolateral region of the gastric mucin-producing epithelial cells. In gastritis, positive NIS staining was observed in these cells both in the presence and absence of Helicobacter pylori. Significantly, NIS expression was absent in gastric cancer, independently of its histological type. Only focal faint NIS expression was detected in the direct vicinity of gastric tumors, i.e., in the histologically intact mucosa, the expression becoming gradually stronger and linear farther away from the tumor. Barrett mucosa with junctional and fundic-type columnar metaplasia displayed positive NIS staining, whereas Barrett mucosa with intestinal metaplasia was negative. NIS staining was also absent in intestinalized gastric polyps.That NIS expression is markedly decreased or absent in case of intestinalization or malignant transformation of the gastric mucosa suggests that NIS may prove to be a significant tumor marker in the diagnosis and prognosis of gastric malignancies and also precancerous lesions such as Barrett mucosa, thus extending the medical significance of NIS beyond thyroid disease.

View details for DOI 10.1186/1471-2407-7-5

View details for Web of Science ID 000244252900001

View details for PubMedID 17214887

View details for PubMedCentralID PMC1794416

Long-term outcomes after invasive breast tumor recurrence (IBTR) in women with DCIS in NSABP B-17 and B-24 Wapnir, I., Dignam, J., Julian, T. B., Land, S., Mamounas, E. P., Anderson, S., Fourchotte, V., Costantino, J., Wolmark, N. AMER SOC CLINICAL ONCOLOGY. 2007

Abstract

A 42-year-old woman presented with a rapidly growing tumor of the breast accompanied by anemia (7.4 g/dL), hypoalbuminemia (1.6 g/dL), and increased alkaline phosphatase (256 U/L). Magnetic resonance imaging of the breast demonstrated a heterogeneous mass composed of verrucous solid components with hemorrhagic areas. There was no evidence of cachexia, and the metastatic workup was negative. Final pathology revealed a 22-cm malignant phyllodes tumor. Hypoalbuminemia and alkaline phosphatase quickly resolved after surgical excision without any further treatment.

View details for PubMedID 17239267

Expression of the Na+/I- symporter (NIS) is markedly decreased or absent in gastric cancer and intestinal metaplastic mucosa of Barrett esophagus BMC CANCER Altorjay, A., Dohan, O., Szilagyi, A., Paroder, M., Wapnir, I. L., Carrasco, N. 2007; 7

Abstract

Locoregional failure after breast-conserving surgery is associated with increased risk of distant disease and death. The magnitude of this risk in patients receiving chemotherapy has not been adequately characterized.Our study population included 2,669 women randomly assigned onto five National Surgical Adjuvant Breast and Bowel Project node-positive protocols (B-15, B-16, B-18, B-22, and B-25), who were treated with lumpectomy, whole-breast irradiation, and adjuvant systemic therapy. Cumulative incidences of ipsilateral breast tumor recurrence (IBTR) and other locoregional recurrence (oLRR) were calculated. Kaplan-Meier curves were used to estimate distant-disease-free survival (DDFS) and overall survival (OS) after IBTR or oLRR. Cox models were used to model survival using clinical and pathologic factors jointly with IBTR or oLRR as time-varying predictors.Four hundred twenty-four patients (15.9%) experienced locoregional failure; 259 (9.7%) experienced IBTR, and 165 (6.2%) experienced oLRR. The 10-year cumulative incidence of IBTR and oLRR was 8.7% and 6.0%, respectively. Most locoregional failures occurred within 5 years (62.2% for IBTR and 80.6% for oLRR). Age, tumor size, and estrogen receptor status were significantly associated with IBTR. Nodal status and estrogen and progesterone receptor status were significantly associated with oLRR. The 5-year DDFS rates after IBTR and oLRR were 51.4% and 18.8%, respectively. The 5-year OS rates after IBTR and oLRR were 59.9% and 24.1%, respectively. Hazard ratios for mortality associated with IBTR and oLRR were 2.58 (95% CI, 2.11 to 3.15) and 5.85 (95% CI, 4.80 to 7.13), respectively.Node-positive breast cancer patients who developed IBTR or oLRR had significantly poorer prognoses than patients who did not experience these events.

View details for DOI 10.1200/JCO.2005.04.3273

View details for Web of Science ID 000237371500012

View details for PubMedID 16648502

Resolution of hypoalbuminemia after excision of malignant phyllodes tumor CLINICAL BREAST CANCER Samiian, L., Daniel, B., Wapnir, I. 2006; 7 (5): 411-412

Abstract

Optical imaging has made it possible to monitor response to anticancer therapies in tumor xenografts. The concept of treating breast cancers with (131)I is predicated on the expression of the Na(+)/I- symporter (NIS) in many tumors and uptake of I- in some. The pattern of (131)I radioablative effects were investigated in an MCF-7 xenograft model dually transfected with firefly luciferase and NIS genes. On Day 16 after tumor cell implantation, 3 mCi of (131)I was injected. Bioluminescent imaging using d-luciferin and a cooled charge-coupled device camera was carried out on Days 1, 2, 3, 7, 10, 16, 22, 29, and 35. Tumor bioluminescence decreased in (131)I-treated tumors after Day 3 and reached a nadir on Day 22. Conversely, bioluminescence steadily increased in controls and was 3.85-fold higher than in treated tumors on Day 22. Bioluminescence in (131)I-treated tumors increased after Day 22, corresponding to tumor regrowth. By Day 35, treated tumors were smaller and accumulated 33% less (99m)TcO(4)(-) than untreated tumors. NIS immunoreactivity was present in <50% of (131)I-treated cells compared to 85-90% of controls. In summary, a pattern of tumor regression occurring over the first three weeks after (131)I administration was observed in NIS-expressing breast cancer xenografts.

View details for DOI 10.2310/7290.2006.00008

View details for PubMedID 16954021

Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in five national surgical adjuvant breast and bowel project node-positive adjuvant breast cancer trials JOURNAL OF CLINICAL ONCOLOGY Wapnir, I. L., Anderson, S. J., Mamounas, E. P., Geyer, C. E., Jeong, J. H., Tan-Chiu, E., Fisher, B., Wolmark, N. 2006; 24 (13): 2028-2037
Bioluminescent-inescent monitoring of NIS-mediated I-131 ablative effects in MCF-7 Xenografts MOLECULAR IMAGING Ghosh, M., Gambhir, S. S., De, A., Nowels, K., Goris, M., Wapnir, I. 2006; 5 (2): 76-84

Abstract

The purpose of this study was to assess the utility of contrast-enhanced breast magnetic resonance imaging (MRI) in identifying lesions unidentified on the craniocaudal projection. The authors reviewed five patients with suspicious mammographic lesions not imaged on the craniocaudal mammogram who were referred for contrast-enhanced MRI and underwent subsequent preoperative needle localization in four of the five cases. Five patients, ages 56 to 69 years, had suspicious lesions identified on mediolateral oblique (MLO) or mediolateral (ML) projections only. Ultrasound did not identify the lesion in any of these cases. MRI identified suspicious breast lesions measuring 5 to 12 mm in size. These were located high on the chest wall or in the upper inner quadrant. Suspicious lesions seen only on the MLO or ML projections may reside high on the chest wall or in the upper inner quadrant. Lesions in these locations may be typically excluded on the craniocaudal projection during mammography. Breast MRI has the advantage of imaging the entire breast and is particularly useful for these lesions. In this series, MRI prevented delay in breast cancer diagnosis.

View details for PubMedID 15327495

Survival after IBTR in NSABP node negative protocols B-13, B-14, B-19, B-20 and B-23. Wapnir, Anderson, S., Mamounas, E., Geyer, C., Hyeon-Jeong, J., Costantino, J., Fisher, B., Wolmark, N. AMER SOC CLINICAL ONCOLOGY. 2005: 8S

Abstract

The Na(+)/I(-) symporter (NIS) is a key plasma membrane protein that mediates active iodide (I(-)) transport in the thyroid, lactating breast, and other tissues. Functional NIS expression in thyroid cancer accounts for the longstanding success of radioactive iodide ((131)I) ablation of metastases after thyroidectomy. Breast cancer is the only other cancer demonstrating endogenous functional NIS expression. Until now, NIS activity in breast cancer metastases (BCM) was unproven.Twenty-seven women were scanned with (99m)TcO(4)(-) or (123)I(-) to assess NIS activity in their metastases. An (131)I dosimetry study was offered to patients with I(-)-accumulating tumors. Selective down-regulation of thyroid NIS was tested in 13 patients with T(3) and in one case with T(3) + methimazole (MMI; blocks I(-) organification). NIS expression was evaluated in index and/or metastatic tumor samples by immunohistochemistry.I(-) uptake was noted in 25% of NIS-expressing tumors (two of eight). The remaining cases did not show NIS expression or activity. Thyroid I(-) uptakes were decreased to

View details for PubMedID 15240514

Magnetic resonance imaging of suspicious breast masses seen on one mammographic view. breast journal Offodile, R. S., Daniel, B. L., Jeffrey, S. S., Wapnir, I., Dirbas, F. M., Ikeda, D. M. 2004; 10 (5): 416-422

View details for PubMedID 15072707

The Na+/I- symporter mediates iodide uptake in breast cancer metastases and can be selectively down-regulated in the thyroid CLINICAL CANCER RESEARCH Wapnir, I. L., Goris, M., Yudd, A., Dohan, O., Adelman, D., Nowels, K., Carrasco, N. 2004; 10 (13): 4294-4302
Elephantiasic prefibial myxedema THYROID Cohen, J. B., Balzer, B., Wapnir, I., McDougall, I. R. 2004; 14 (3): 237-238

Abstract

Extrathyroidal cancers could potentially be targeted with (131)I, if the Na(+)/I(-) symporter (NIS) were functional. Using immunohistochemical methods we probed 1278 human samples with anti-NIS antibody, including 253 thyroid and 169 breast conventional whole tissue sections (CWTS). Four high density tissue microarrays containing a wide variety of breast lesions, normal tissues, and carcinoma cores were tested. The results of the normal microarray were corroborated in 50 CWTS. Nineteen of 34 normal tissues, including bladder, colon, endometrium, kidney, prostate, and pancreas, expressed NIS. Nineteen of 25 carcinomas demonstrated NIS immunopositivity; 55.7% of 479 carcinoma microarray cores expressed NIS, including prostate (74%), ovary (73%), lung (65%), colon (62.6%), and endometrium (56%). NIS protein was present in 75% benign thyroid lesions, 73% thyroid cancers, 30% normal-appearing, peritumoral breasts, 88% ductal carcinomas in situ, and 76% invasive breast carcinoma CWTS. Comparatively, breast microarray cores had lower immunoreactivity. Plasma membrane immunopositivity was confirmed in thyrocytes, salivary ductal, gastric mucosa, and lactating mammary cells. In other tissues, immunoreactivity was predominantly intracellular, particularly in malignant lesions. Thus, NIS is present in many normal epithelial tissues and is predominantly expressed intracellularly in many carcinomas. Elucidating the regulatory mechanisms that render NIS functional in extrathyroidal carcinomas may make (131)I therapy feasible.

View details for DOI 10.1210/jc.2002-021544

View details for PubMedID 12679487

The effect acute sleep deprivation experienced in a simulated on-call period on surgical performance 18th Annual Meeting of the Associated-Professional-Sleep-Societies Woo, R. K., Greco, R. S., Wapnir, I. L., Colrain, I. M. AMER ACAD SLEEP MEDICINE. 2004: 167167

Abstract

Angiogenesis has emerged as an indicator of metastatic potential in invasive breast cancer. Exponential tumor growth and the appearance of metastasis are observed as new microvessels form. We postulated that the relevance of angiogenesis would be enhanced if analyzed as a function of tumor volume rather than greatest diameter alone and that microvessel counts would proportionately increase as does volume. Since tumors are three-dimensional solids, volume was calculated using the formula for an ellipsoid, V = pi/6 (a x b x c). Sixty-four tumors < or = 2.5 cm were studied and analyzed in 5 mm incremental ranges. Mean microvessel counts did not vary significantly among these tumor size groups. However, analysis of microvessel counts as a function of tumor volume decreased from 947.1/cm3 (0-0.5 cm) to 18.1/cm3 (2.1-2.5 cm), a greater than 50-fold difference. High microvessel density in small cancers supports the notion of metastasis as an early event, making these small tumors perhaps ideal targets for antiangiogenic agents.

View details for PubMedID 11469933

Immunohistochemical profile of the sodium/iodide symporter in thyroid, breast, and other carcinomas using high density tissue microarrays and conventional sections JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Wapnir, I. L., van de Rijn, M., Nowels, K., Amenta, P. S., Walton, K., Montgomery, K., Greco, R. S., Dohan, O., Carrasco, N. 2003; 88 (4): 1880-1888

Abstract

The sodium/iodide symporter mediates active iodide transport in both healthy and cancerous thyroid tissue. By exploiting this activity, radioiodide has been used for decades with considerable success in the detection and treatment of thyroid cancer. Here we show that a specialized form of the sodium/iodide symporter in the mammary gland mediates active iodide transport in healthy lactating (but not in nonlactating) mammary gland and in mammary tumors. In addition to characterizing the hormonal regulation of the mammary gland sodium/iodide symporter, we demonstrate by scintigraphy that mammary adenocarcinomas in transgenic mice bearing Ras or Neu oncogenes actively accumulate iodide by this symporter in vivo. Moreover, more than 80% of the human breast cancer samples we analyzed by immunohistochemistry expressed the symporter, compared with none of the normal (nonlactating) samples from reductive mammoplasties. These results indicate that the mammary gland sodium/iodide symporter may be an essential breast cancer marker and that radioiodide should be studied as a possible option in the diagnosis and treatment of breast cancer.

View details for Web of Science ID 000165473800029

View details for PubMedID 10932223

The inverse relationship between microvessel counts and tumor volume in breast cancer. breast journal Wapnir, I. L., Barnard, N., Wartenberg, D., Greco, R. S. 2001; 7 (3): 184-188

Abstract

Lumpectomy with axillary dissection (LAD) has taken its place alongside mastectomy (M) as the treatment of choice for stage I and II breast cancer. Its appeal is based on lessening disfigurement and thus improving quality of life.We used the SF-36 Health Survey modified with ten questions relevant to breast cancer surgery to evaluate whether quality of life with LAD was better than with mastectomy in women with stage I and II disease. The additional questions addressed satisfaction with intimate relationships and sexuality, and explored impact on the way women dress, use bathing suits, hug people, are comfortable with nudity, and rate their sexual drive and sexual responsiveness.LAD was not associated with statistically significant better quality-of-life scores on any SF-36 questions, except vitality (P = .02). No differences were noted in the areas of intimacy and sexual satisfaction. LAD patients reported significant differences in matters of dress, use of bathing suits, hugging, comfort with nudity, and sexual drive compared to patients undergoing mastectomy.The SF-36 health survey detected few differences in quality of life measures between patients with LAD and those with mastectomy. However, LAD impacts favorably on the way women dress, on comfort with nudity, and on sexual drive.

View details for Web of Science ID 000080715300009

View details for PubMedID 10379856

The mammary gland iodide transporter is expressed during lactation and in breast cancer NATURE MEDICINE Tazebay, U. H., Wapnir, I. L., Levy, O., Dohan, O., Zuckier, L. S., Zhao, Q. H., Deng, H. F., Amenta, P. S., Fineberg, S., Pestell, R. G., Carrasco, N. 2000; 6 (8): 871-878

Abstract

Excessive deposition of extracellular matrix or neomatrix is a characteristic of desmoplastic invasive breast carcinomas. Type I and III collagens are abundant neomatrix components. Archival breast tissue sections were studied using 35S-labeled cDNA probes for alpha 1(I) and alpha 1(III) procollagen and in situ hybridization. Among the 33 invasive breast cancers, hybridization was seen forming a gradient-like pattern in fibroblasts closest to tumor cells. In the 10 ductal carcinomas in situ studied, a ring-like pattern of hybridization was seen in proximity to the basement membrane zone. Adjacent normal and benign tissues did not demonstrate the patterns of hybridization described in malignant tissues. Gene expression for neomatrix interstitial collagens occurs before there is evidence of invasion in carcinoma of the breast.

View details for Web of Science ID A1997YE40000005

View details for PubMedID 9371230

Subtle differences in quality of life after breast cancer surgery 82nd Surgical Forum of the American-College-of-Surgeons Wapnir, I. L., Cody, R. P., Greco, R. S. SPRINGER. 1999: 35966

Abstract

Breast cancers are three dimensional solids but very few are spherical. We hypothesized that calculations based on the greatest diameter would not accurately reflect tumor volume and that three dimensional measurements would affect tumor staging.165 invasive carcinomas measuring 2.5 cm or less and having three measured diameters (a > or = b > or = c) noted were evaluated. Tumor volume was calculated using four geometric models: the spherical 4/3 pi (a/2)3, prolate spheroid 4/3 pi (a/2) (c/2)2, oblate spheroid 4/3 pi (a/2)2 (b/2), and ellipsoid 4/3 pi (a/2 x b/2 x c/2). The ellipsoid correctly determined the volume for any tumor shape. All cases were stratified according to the TNM staging system. Differences in mean volume calculated as a sphere and ellipsoid for each tumor subclass were analyzed using Student's T test. The reclassification of tumors by the ellipsoid formula was determined.Seventy-six (46.1%) had tumors with three different diameters while only six (3.6%) were true spheres having three identical diameters. Mean tumor volume analysis of T1a, T1b, T1c, and T2 tumors demonstrated a statistically significant overestimation of volume when utilizing the sphere formula instead of the ellipsoid formula (p < 0.05). The differences in volume were more dramatic as the diameters increased. A total of 41 tumors were moved into smaller T subclasses including 10 node positive patients.Tumor volume analysis demonstrates that use of only the greatest diameter poorly reflects the true volume of a lesion and consistently overestimates volume. The ellipsoid formula accurately calculates volume for these three dimensional tumors and when utilized has significant relevance to staging small invasive breast cancers.

View details for Web of Science ID A1996VR62000002

View details for PubMedID 8932872

The verbal abuse of resident physicians Disease Management and Clinical Outcomes Wapnir IL, Cody RP, Greco RS 1999; 1 (6): 203-206

Abstract

Matrix metalloproteinase-2 (MMP-2), a zymogen requiring proteolytic activation for catalytic activity, has been implicated broadly in the invasion and metastasis of many cancer model systems, including human breast cancer (HBC). MMP-2 has been immunolocalized to carcinomatous human breast, where the degree of activation of MMP-2 correlates well with tumor grade and patient prognosis. Using Matrigel assays, we have stratified HBC cell lines for invasiveness in vitro, and compared this to their potential for metastatic spread in nude mice. HBC cell lines expressing the mesenchymal marker protein vimentin were found to be highly invasive in vitro, and tended to form metastases in nude mice. We have further discovered that culture on collagen-I gels (Vitrogen; Vg) induces MMP-2-activator in highly invasive but not poorly invasive HBC cell lines. As seen for other MMP-2-activator inducing regimens, this induction requires protein synthesis and an intact MMP-2 hemopexin-like domain, appears to be mediated by a cell surface activity, and can be inhibited by metalloproteinase inhibitors. The induction is highly specific to collagen I, and is not seen with thin coatings of collagen I, collagen IV, laminin, or fibronectin, or with 3-dimensional gels of laminin, Matrigel, or gelatin. This review focuses on collagen I and MMP-2, their localization and source in HBC, and their relationship(s) to MMP-2 activation and HBC metastasis. The relevance of collagen I in activation of MMP-2 in vivo is discussed in terms of stromal cell: tumor cell interaction for collagen I deposition, MMP-2 production, and MMP-2-activation. Such cooperativity may exist in vivo for MMP-2 participation in HBC dissemination. A more complete understanding of the regulation of MMP-2-activator by type I collagen may provide new avenues for improved diagnosis and prognosis of human breast cancer.

View details for Web of Science ID A1994PK88900022

View details for PubMedID 7881112

Collagen gene expression in the neomatrix of carcinoma of the breast INVASION & METASTASIS Wapnir, I. L., Southard, H., Chen, G. H., Friedman, J., BOYD, C. D., Amenta, P. S. 1996; 16 (6): 308-316

Abstract

Mammographic architectural distortion occurred at the operative site in 86 percent of lumpectomy patients and in 34 percent of biopsy patients during the first year (P < 0.001). These changes can mimic carcinoma and may be slow to resolve.

View details for PubMedID 8380491

Three dimensional staging of breast cancer BREAST CANCER RESEARCH AND TREATMENT Wapnir, I. L., WARTENBERG, D. E., Greco, R. S. 1996; 41 (1): 15-19

Abstract

The concept of prophylactic mastectomy was nurtured in the shadow of the radical mastectomy. It evolved as preferable to the mutilation caused by the procedure. It developed during a time when the difference between benignancy and malignancy was not as clear and when patients with benign disease were thought to be at significant risk. The idea of surgical prophylaxis accompanied by a superior cosmetic result, in comparison to the radical mastectomy is a noble one. In retrospect, however, it is clear that the indications were ill defined, based often on unfounded risk and predicated on patient and physician anxiety. The scope of risk in carcinoma of the breast has been narrowed, with new information identifying only specific subsets of women with proliferative types of benign disease as more susceptible to the subsequent development of carcinoma. Extensive reviews of material taken at biopsy that had been validated longitudinally have provided data to substantiate this contention. The concept of familial high risk must take into account the number of affected family members, at age diagnosis, menopausal status and bilaterality. The majority of indicants that motivated and propitiated the performance of the bulk of prophylactic mastectomies have lost their relevance. Prophylactic mastectomy for carcinoma, therefore, can perhaps be reserved for women with biopsy-proved, high-risk lesions or an exceptional familial risk, or both, or hereditary risk. Such women must choose for themselves and accept the uncertainty of hypothetic risk reduction, life-long continued surveillance and an altered body image. Guiding patients in the decision should involve a multidisciplinary team composed of a surgical oncologist, geneticist, pathologist, psychotherapist and plastic surgeon. As a concept, the reduction of risk is appealing, but remains yet to prove itself superior to rigorous clinical surveillance with high-quality mammography. The experience reflected in the literature of a seemingly low rate of subsequent carcinoma cannot be judged, because it seems that operations were applied indiscriminantly to patients selected by unknown means and from an unknown population pool. Success based on protecting those not at increased risk only invalidates the operation further. Most surgical and medical oncologists recognize that carcinoma of the breast is either localized or disseminated at the time of the initial diagnosis.(ABSTRACT TRUNCATED AT 400 WORDS)

View details for Web of Science ID A1990DR88900018

View details for PubMedID 2200150

Pathologic differences in nonpalpable breast cancers detected by xeromammography and film screen mammography Breast Disease Wapnir IL, Fang M, Zicherman B, Greco RS 1996; 9 (4): 203-210

Abstract

In 9 of 45 patients treated for dual vascular injuries of the lower extremity, concomitant fasciotomies were performed at the time of initial surgery for associated soft tissue injury, fracture, or prolonged ischemia. Eight other patients developed compartment syndrome requiring delayed fasciotomy. In seven of them, vein was either ligated or the repaired vein became occluded. In the eighth patient, peripheral venous hypertension was caused by massive swelling of the thigh. In the laboratory, compartment pressure was monitored by wick catheter in 24 hind limbs of 12 dogs subjected to experimental conditions simulating vascular injuries and their management. There was a significant increase in compartment pressure in a group that simulated arterial and venous injuries managed by arterial repair and venous outflow obstruction. Based on our study, we suggest that obstruction to venous drainage and venous hypertension are major factors in the development of compartment syndrome in dual vascular injuries of the lower extremity.

View details for Web of Science ID A1989AK11300011

View details for PubMedID 2757141

Superior quality of life following lumpectomy-axillary dissection in patients with stage I and stage II beast cancer Surgical Forum Wapnir IL, Cody RP, Greco RS 1996; XLVII: 635-636

View details for Web of Science ID A1988N215900039

View details for PubMedID 3363001

Local recurrence after breast conservation Current Surgery Wapnir IL 1996; 53 (161): 8-13

Abstract

Forty-eight adult patients with isolated splenic trauma from blunt injury were analyzed during a six year period (1980 to 1986). Early laparotomy was performed upon 38 patients and splenic preservation was accomplished in 18. The remaining ten patients who were hemodynamically stable were managed nonoperatively with close monitoring. Splenic injuries were confirmed by one of the imaging methods, such as computed tomography, radionuclide scan or ultrasound. One patient with known hepatic cirrhosis underwent embolization of the splenic artery and recovered. Nonoperative treatment failed in seven of the remaining nine patients, mandating an exploratory laparotomy between the third and tenth day of admission. In six of the seven patients, splenic preservation was unsuccessful, necessitating a splenectomy. The length of hospital stay was longer for this latter group (a mean of 15.8 days) than for patients who had splenorrhaphy (a mean of 7.5 days), or splenectomy (a mean of 8.7 days, p less than 0.001). Patients managed nonoperatively required more units of blood compared with those undergoing splenorrhaphy (4.1 units versus 1.7 units, p less than 0.01). A review of the literature reveals that splenic preservation is possible in less than 25 per cent of the patients who fail to respond to nonoperative management. We conclude that splenic injuries after blunt trauma in adults are treated best by early laparotomy in order to achieve maximal splenic preservation.

View details for Web of Science ID A1988M333100010

View details for PubMedID 3344454

Stage II ductal carcinoma arising in a fibroadenoma Breast Disease Wapnir, I., Barnard N 1995; 8: 57-61

Abstract

The authors report their experience with 14 patients with portal vein injuries (1976-1986) treated at a level I trauma center. Seven patients (50%) survived and included six of 10 patients (60%) who had venorrhaphy and one in whom the portal vein was ligated. Associated injuries were present in all the patients (mean Abdominal Trauma Index: 39.5) and accounted for the high mortality rate. Follow-up data after repair or ligation of the portal vein seldom are reported in the literature. The authors studied all three patients who survived portal venorrhaphy since 1982 by real-time ultrasonography. Patency of the repair could be established in two patients. In the third patient postvenorrhaphy thrombosis was diagnosed by ultrasonographic examination. Sequential ultrasonographic examinations demonstrated resolution of the thrombus on anticoagulant therapy. Ultrasonography provides a noninvasive and easily reproducible method of studying the portal vein after repair.

View details for Web of Science ID A1987L074700008

View details for PubMedID 3318729

COLLAGEN-INDUCED MMP-2 ACTIVATION IN HUMAN BREAST-CANCER BREAST CANCER RESEARCH AND TREATMENT Thompson, E. W., Yu, M., Bueno, J., Jin, L., Maiti, S. N., PALAOMARCO, F. L., Pulyaeva, H., Tamborlane, J. W., TIRGARI, R., Wapnir, I., Azzam, H. 1994; 31 (2-3): 357-370

Abstract

Among the surgical complications of intravenous drug addiction, pyogenic splenic abscess is considered to be a rare entity. A review of the literature reveals only 24 cases of splenic abscess secondary to this particular etiology. The authors report five patients with intravenous drug addiction who underwent splenectomy for pyogenic splenic abscess within 1 year. Fever and abdominal pain were the only constant physical signs. Three patients had associated infective endocarditis, and the other two patients sustained blunt trauma to the left side of the trunk weeks earlier. Computed tomography (CT) and ultrasound were diagnostic in all five patients preoperatively, and they were complementary when combined. Four of the five patients had Staphylococcus aureus septicemia at the time of splenectomy. Three patients recovered from their operations, and the other two, both with endocarditis, died postoperatively from causes unrelated to splenic abscess and splenectomy. A high index of suspicion is warranted in this susceptible group of patients with vague abdominal signs and persistent sepsis to rule out splenic suppuration. The noninvasive imaging methods, CT scan and ultrasound, facilitate early diagnosis in these patients.

View details for Web of Science ID A1987H551200010

View details for PubMedID 3579050

Mammographic changes following biopsy and lumpectomy-breast irradiation. New Jersey medicine : the journal of the Medical Society of New Jersey Wapnir, I. L., Alden-Corbett, S., Zicherman, B., Greco, R. S. 1993; 90 (1): 55-59

View details for PubMedID 4005025

A REAPPRAISAL OF PROPHYLACTIC MASTECTOMY SURGERY GYNECOLOGY & OBSTETRICS Wapnir, I. L., Rabinowitz, B., Greco, R. S. 1990; 171 (2): 171-184

Abstract

Tuberculosis of the breast was diagnosed in this 63-year-old woman 14 years after she was treated for tuberculous pericarditis. Case history and a review of the literature are presented.

View details for Web of Science ID A1985ATV0100019

View details for PubMedID 4060074

COMPARTMENT SYNDROME IN COMBINED ARTERIAL AND VENOUS INJURIES OF THE LOWER-EXTREMITY AMERICAN JOURNAL OF SURGERY Shah, P. M., Wapnir, I., Babu, S., Stahl, W. M., CLAUSS, R. H. 1989; 158 (2): 136-141

View details for Web of Science ID A1977DU41100010

View details for PubMedID 142678

Residual tumor and breast biopsy margins Breast Disease Wapnir, I., Bancila E, Devereux DF, Grecor RS 1989; 2: 81-86
ASYMMETRICAL BREASTS IN AN ADOLESCENT PLASTIC AND RECONSTRUCTIVE SURGERY Wapnir, I., Rabinowitz, B., Snyderman, R. 1988; 81 (5): 813-813
NONOPERATIVE MANAGEMENT VERSUS EARLY OPERATION FOR BLUNT SPLENIC TRAUMA IN ADULTS SURGERY GYNECOLOGY & OBSTETRICS NALLATHAMBI, M. N., Ivatury, R. R., Wapnir, I., Rohman, M., Stahl, W. M. 1988; 166 (3): 252-258
PORTAL-VEIN INJURIES - NONINVASIVE FOLLOW-UP OF VENORRHAPHY ANNALS OF SURGERY Ivatury, R. R., NALLATHAMBI, M., LANKIN, D. H., Wapnir, I., Rohman, M., Stahl, W. M. 1987; 206 (6): 733-737
PYOGENIC SPLENIC ABSCESS IN INTRAVENOUS DRUG-ADDICTION AMERICAN SURGEON NALLATHAMBI, M. N., Ivatury, R. R., LANKIN, D. H., Wapnir, I. L., Stahl, W. M. 1987; 53 (6): 342-346
[Gastroesophageal reflux in children. Experience in 100 cases treated by Nissen's fundoplication]. Boletn mdico del Hospital Infantil de Mxico Prez-Fernndez, L., Pea-Rodrguez, A., Wapnir, I. 1985; 42 (4): 256-265
LATENT MAMMARY TUBERCULOSIS - A CASE-REPORT SURGERY Wapnir, I. L., PALLAN, T. M., Gaudino, J., Stahl, W. M. 1985; 98 (5): 976-978
Muerte inesperada y sindrome de muerte subita en la infancia PAtologia (Mexico) Ridaura-Sanz C, Wapnir-Michalewicz IL, Lopez-Corella E, Mendoza-Lopez E 1980; 18: 341-350
MAGNESIUM-METABOLISM IN EXPERIMENTAL DIABETES-MELLITUS DIABETES Fort, P., Lifshitz, F., Wapnir, I. L., Wapnir, R. A. 1977; 26 (9): 882-886