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Neo-adjuvant doxorubicin and cyclophosphamide followed by paclitaxel in triple-negative breast cancer among BRCA1 mutation carriers and non-carriers

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Abstract

The purpose of this study was to assess pathological complete response and whether it serves a surrogate for survival among patients receiving neo-adjuvant doxorubicin–cyclophosphamide followed by paclitaxel for triple-negative breast cancer with respect to BRCA1 mutation status. From a neo-adjuvant systemic therapy database of 588 breast cancer cases, 80 triple-negative cases who had undergone BRCA genotyping were identified. Logistic regression model was fitted to examine the association between BRCA1 status and pathological complete response. Survival outcomes were evaluated using Kaplan–Meier method, differences between study groups calculated by log-rank test. Thirty-four BRCA1 carriers and 43 non-carriers were identified. The BRCA1 carriers had pathological complete response rate of 68 % compared with 37 % among non-carriers, p = 0.01. Yet this did not translate into superior survival for BRCA1 carriers compared with non-carriers. No difference in relapse-free survival were noted among those with or without pathological complete response in BRCA1 carriers regardless of pathological complete response status (Log-rank p = 0.25), whereas in the non-carrier cohort, relapse-free survival was superior for those achieving pathological complete response (Log-rank p < 0.0001). Response to neo-adjuvant systemic therapy differed in BRCA1-associated triple-negative breast cancer compared with triple-negative non-carriers, with a higher rate of pathological complete response. However, compared with non-carrier triple-negative breast cancer, pathological complete response was not a surrogate for superior relapse-free survival in BRCA1 patients. Future studies using specific chemotherapy regimens may provide further improvements in outcomes.

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Acknowledgments

The authors thank Karen Gelmon for her guidance, input, and review of the manuscript.

Author’s contributions

S Paluch-Shimon, E. Friedman, R. Berger, M. Papa, M. Dadiani, and B. Kaufman contributed to conception and design, acquisition of data, analysis and interpretation of data, drafting the manuscript, and revising it critically for important intellectual content. M. Shabtai, D. Zippel, M. Gutman, N. Friedman A. Yosepovich, and T. Modiano significantly contributed to acquisition of data and revising manuscript. T. Golan and R. Catane contributed to drafting the manuscript and revising it critically. All authors provided final approval of the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Authors and Affiliations

  1. Institute of Oncology, The Chaim Sheba Medical Center, 52621, Tel Hashomer, Israel

    Shani Paluch-Shimon, Raanan Berger, Maya Dadiani, Neil Friedman, Talia Golan, Raphael Catane, Tami Modiano & Bella Kaufman

  2. The Dr. Pinchas Borenstein Talpiot Medical Leadership Program, The Chaim Sheba Medical Center, Tel Hashomer, Israel

    Shani Paluch-Shimon

  3. The Suzanne Levy Gertner Oncogenetics Unit, The Chaim Sheba Medical Center, Tel Hashomer, Israel

    Eitan Friedman

  4. Department of Surgery, The Chaim Sheba Medical Center, Tel Hashomer, Israel

    Moshe Shabtai, Dov Zippel & Mordechai Gutman

  5. Department of Pathology, The Chaim Sheba Medical Center, Tel Hashomer, Israel

    Ady Yosepovich

  6. The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Shani Paluch-Shimon, Eitan Friedman, Raanan Berger, Moshe Papa, Moshe Shabtai, Dov Zippel, Mordechai Gutman, Talia Golan, Ady Yosepovich, Raphael Catane, Tami Modiano & Bella Kaufman

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  1. Shani Paluch-Shimon
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Paluch-Shimon, S., Friedman, E., Berger, R. et al. Neo-adjuvant doxorubicin and cyclophosphamide followed by paclitaxel in triple-negative breast cancer among BRCA1 mutation carriers and non-carriers. Breast Cancer Res Treat 157, 157–165 (2016). https://doi.org/10.1007/s10549-016-3800-5

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