Fourquet Alain, Stoppa-Lyonnet Dominique, Kirova Youlia M, Sigal-Zafrani Brigitte, Asselain Bernard
Departments of Radiation Oncology, Institut Curie, Paris, France.
Am J Clin Oncol. 2009 Apr;32(2):127-31. doi: 10.1097/COC.0b013e31817f9e1c.
BRCA1/2 germline mutations are associated with impaired DNA double-strand break repair. We tested whether breast cancers in BRCA1/2 mutation carriers were more responsive to induction treatments than in noncarriers.
The BRCA1 and BRCA2 genes were screened for germline mutation in a retrospective cohort of 90 patients (with 93 tumors) with a family history of breast and/or ovarian cancer, treated with induction anthracycline-containing chemotherapy and/or radiotherapy. Median tumor size was 40 mm. Clinical responses and breast preservation rates were correlated to BRCA1/2 mutation status, and to other clinical and pathologic factors.
A complete clinical response was achieved in 15/39 (46%) BRCA1/2-mutated tumors and in 7/54 (17%) nonmutated tumors (P = 0.008). Complete or major clinical response rate was observed in 55 of the 74 tumors treated with induction chemotherapy (74.3%). The overall complete or major clinical response rate in the tumors treated with induction radiotherapy was 68% (13/19 tumors). Following induction treatment by either chemotherapy or radiotherapy, more breast-conserving treatments could be performed in mutation carriers than in noncarriers: the rates of breast preservation were 82% in BRCA1/2-mutated tumors and 63% in nonmutated tumors, respectively (P = 0.045). BRCA1 mutation was the sole predictor of breast conservation.
Breast conservation after induction treatment was higher in BRmut+ tumors, and clinical response was related to aggressive tumor features correlated with BRCA1/2 mutations. This suggests that impaired repair mechanisms related to the BRCA1/2 mutations increased the chemosensitivity and radiosensitivity of large breast cancers. Further studies will need to determine the long-term outcome in these patients.
BRCA1/2基因种系突变与DNA双链断裂修复受损相关。我们测试了携带BRCA1/2突变的乳腺癌患者对诱导治疗的反应是否比非携带者更敏感。
对90例（93个肿瘤）有乳腺癌和/或卵巢癌家族史、接受含蒽环类化疗和/或放疗诱导治疗的患者进行回顾性队列研究，筛查BRCA1和BRCA2基因的种系突变。肿瘤中位大小为40mm。将临床反应和保乳率与BRCA1/2突变状态以及其他临床和病理因素相关联。
15/39（46%）携带BRCA1/2突变的肿瘤实现了完全临床缓解，7/54（17%）未突变的肿瘤实现了完全临床缓解（P = 0.008）。在接受诱导化疗的74个肿瘤中，55个（74.3%）观察到完全或主要临床缓解率。接受诱导放疗的肿瘤总体完全或主要临床缓解率为68%（13/19个肿瘤）。在接受化疗或放疗诱导治疗后，突变携带者比非携带者能够进行更多的保乳治疗：BRCA1/2突变肿瘤的保乳率为82%，未突变肿瘤的保乳率为63%，分别（P = 0.045）。BRCA1突变是保乳的唯一预测因素。
诱导治疗后，BR突变阳性肿瘤的保乳率更高，临床反应与与BRCA1/2突变相关的侵袭性肿瘤特征有关。这表明与BRCA1/2突变相关的修复机制受损增加了大型乳腺癌的化疗敏感性和放射敏感性。需要进一步研究来确定这些患者的长期预后。
