Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel.
Faculty of Medicine Tel-Aviv University, Tel-Aviv, Israel.
Breast Cancer Res Treat. 2024 Jun;205(2):241-248. doi: 10.1007/s10549-024-07247-4. Epub 2024 Feb 12.
Whether germline BRCA (gBRCA) pathogenic variants (PV) affect prognosis of women with triple negative breast cancer (TNBC) and whether it has implications for treatment decisions in the neoadjuvant setting is unclear.
This is a retrospective two-center cohort study comprising all women with early stage TNBC who have completed genetic testing and were treated with neoadjuvant dose-dense doxorubicin and cyclophosphamide followed by paclitaxel and carboplatin. All eligible patients treated between 10.2014 and 3.2020 were included. Data on clinico-pathological, pathological response, overall survival (OS) and disease-free survival (DFS) were evaluated. Differences in clinico-pathological features and outcomes were analyzed according to gBRCA status.
Sixty-four women were included in the final analysis, of which 31 had gBRCA PV (gBRCA carriers) and 33 were gBRCA wild-type. Clinico-pathological characteristics were similar between both groups. The odds for pathological complete response (pCR) were significantly higher in gBRCA carriers (74.2%) compared to BRCA wild-type women (48.5%), p = 0.035. At a median follow-up of 30 months, gBRCA carriers had significantly favorable OS (HR = 8.64, 95% CI 1.08-69.21, p = 0.042). The difference in DFS did not reach statistical significance (HR = 7.4, 95% CI 0.91-60.27, p = 0.062). The favorable OS for gBRCA carriers remained significant in multivariate analysis (p = 0.029) and was noted regardless of pathological response (p = 0.018).
Compared to wild-type, gBRCA carriers with locally advanced TNBC treated with neoadjuvant chemotherapy containing carboplatin had a higher pCR rate and better outcomes. These results strengthen the contention that gBRCA status should be considered when tailoring treatment decisions in women with locally advanced TNBC.
胚系 BRCA（gBRCA）致病性变异（PV）是否影响三阴性乳腺癌（TNBC）女性的预后，以及它是否对新辅助治疗方案中的治疗决策有影响尚不清楚。
这是一项回顾性的两中心队列研究，纳入了所有完成基因检测并接受新辅助剂量密集多柔比星和环磷酰胺序贯紫杉醇和卡铂治疗的早期 TNBC 女性患者。所有符合条件的患者均于 2014 年 10 月至 2020 年 3 月接受治疗。评估了临床病理特征、病理反应、总生存期（OS）和无病生存期（DFS）的数据。根据 gBRCA 状态分析了临床病理特征和结局的差异。
最终纳入 64 例患者进行分析，其中 31 例为 gBRCA 致病性变异携带者（gBRCA 携带者），33 例为 gBRCA 野生型。两组的临床病理特征相似。gBRCA 携带者的病理完全缓解（pCR）率明显高于 BRCA 野生型女性（74.2%比 48.5%，p=0.035）。中位随访 30 个月时，gBRCA 携带者的 OS 明显较好（HR=8.64，95%CI 1.08-69.21，p=0.042）。DFS 差异无统计学意义（HR=7.4，95%CI 0.91-60.27，p=0.062）。多因素分析中 gBRCA 携带者的 OS 较好仍有统计学意义（p=0.029），且与病理反应无关（p=0.018）。
与野生型相比，接受含卡铂的新辅助化疗治疗的局部晚期 TNBC 女性中，gBRCA 携带者的 pCR 率更高，结局更好。这些结果进一步证实了在局部晚期 TNBC 女性中，gBRCA 状态应作为治疗决策的考虑因素。
