Paluch-Shimon Shani, Friedman Eitan, Berger Raanan, Papa Moshe, Dadiani Maya, Friedman Neil, Shabtai Moshe, Zippel Dov, Gutman Mordechai, Golan Talia, Yosepovich Ady, Catane Raphael, Modiano Tami, Kaufman Bella
Institute of Oncology, The Chaim Sheba Medical Center, 52621, Tel Hashomer, Israel.
The Dr. Pinchas Borenstein Talpiot Medical Leadership Program, The Chaim Sheba Medical Center, Tel Hashomer, Israel.
Breast Cancer Res Treat. 2016 May;157(1):157-65. doi: 10.1007/s10549-016-3800-5. Epub 2016 Apr 25.
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.
本研究旨在评估接受新辅助多柔比星-环磷酰胺序贯紫杉醇治疗的三阴性乳腺癌患者中,病理完全缓解情况及其是否可作为生存替代指标,并探讨其与BRCA1突变状态的关系。从一个包含588例乳腺癌病例的新辅助全身治疗数据库中,确定了80例接受过BRCA基因分型的三阴性乳腺癌病例。采用逻辑回归模型检验BRCA1状态与病理完全缓解之间的关联。使用Kaplan-Meier方法评估生存结局,通过对数秩检验计算研究组之间的差异。共确定了34例BRCA1携带者和43例非携带者。BRCA1携带者的病理完全缓解率为68%,而非携带者为37%,p = 0.01。然而,与非携带者相比,BRCA1携带者并未表现出更好的生存情况。无论病理完全缓解状态如何,BRCA1携带者中病理完全缓解者与未缓解者的无复发生存率无差异(对数秩p = 0.25);而在非携带者队列中,达到病理完全缓解者的无复发生存率更高(对数秩p < 0.0001)。与三阴性非携带者相比,BRCA1相关的三阴性乳腺癌对新辅助全身治疗的反应不同,病理完全缓解率更高。然而,与非携带者三阴性乳腺癌相比,病理完全缓解并非BRCA1患者无复发生存率更高的替代指标。未来使用特定化疗方案的研究可能会进一步改善治疗结局。