激素受体阳性乳腺癌新辅助化疗后突变状态与较高的病理完全缓解率相关。
Mutational Status is Associated with a Higher Rate of Pathologic Complete Response After Neoadjuvant Chemotherapy in Hormone Receptor-Positive Breast Cancer.
机构信息
Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Breast Medicine Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
出版信息
Ann Surg Oncol. 2023 Dec;30(13):8412-8418. doi: 10.1245/s10434-023-14319-0. Epub 2023 Oct 5.
BACKGROUND
Pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) occurs in up to 20% of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancers. Whether this differs among BRCA mutation carriers is uncertain. This study compared pCR between BRCA1/2 mutation carriers and matched sporadic control subjects.
METHODS
From November 2013 to January 2022, this study identified 522 consecutive women with clinical stage I to III HR+/HER2- breast cancer treated with NAC and surgery. The study matched BRCA1/2 mutation carriers 1:2 to non-carriers in terms of age, clinical tumor (cT) and nodal (cN) stage, and differentiation. Two-sample non-parametric tests compared baseline characteristics. Multivariable logistic regression assessed pCR (i.e., ypT0/ispN0) by BRCA1/2 mutational status.
RESULTS
Of the 522 women (median age, 50 years), 59 had BRCA1/2 mutations, 78% of which were clinically node positive. Anthracycline-based NAC was administered to 97%. More BRCA1/2 mutation carriers were younger, had cT1 tumors, and had poorly differentiated disease. After matching, 58 BRCA1/2 mutation carriers were similar to 116 non-carriers in terms of age (p = 0.6), cT (p = 0.9), cN stage (p = 0.7), and tumor differentiation (p > 0.9). Among the mutation carriers, the pCR rate was 15.5% for BRCA1/2, 38% (8/21) for BRCA1, and 2.7% (1/37) for BRCA2 versus 7.8% (9/116) for the non-carriers (p < 0.001). After NAC, 5 (41.7%) of the 12 BRCA1 mutation carriers converted to pN0 versus 10 (37%) of the 27 BRCA2 mutation carriers and 19 (20.9%) of the 91 non-carriers (p = 0.3). In the multivariable analysis, BRCA1 mutation status was associated with higher odds of pCR than non-carrier status (odds ratio [OR] 6.31; 95% confidence interval [CI] 1.95-20.5; p = 0.002), whereas BRCA2 mutation status was not (OR 0.45; 95% CI 0.02-2.67; p = 0.5).
CONCLUSIONS
This study showed that BRCA1 mutation carriers with HR+/HER2- breast cancers have a higher rate of pCR than sporadic cancers and may derive greater benefit from chemotherapy. The use of NAC to downstage these patients should be considered.
背景
新辅助化疗（NAC）后达到病理完全缓解（pCR）的激素受体阳性（HR+）/人表皮生长因子受体 2 阴性（HER2-）乳腺癌患者占比高达 20%。BRCA 基因突变携带者是否存在差异尚不确定。本研究比较了 BRCA1/2 基因突变携带者与匹配的散发性对照患者的 pCR 情况。
方法
2013 年 11 月至 2022 年 1 月，本研究纳入了 522 例接受 NAC 和手术治疗的临床分期 I 至 III 期 HR+/HER2-乳腺癌患者。研究按年龄、临床肿瘤（cT）和淋巴结（cN）分期和分化程度，1:2 匹配 BRCA1/2 基因突变携带者和非携带者。两样本非参数检验比较基线特征。多变量逻辑回归评估 BRCA1/2 突变状态与 pCR（ypT0/ispN0）的关系。
结果
在 522 例患者中（中位年龄 50 岁），59 例存在 BRCA1/2 基因突变，其中 78%为临床淋巴结阳性。97%的患者接受了蒽环类药物为基础的 NAC。BRCA1/2 基因突变携带者更年轻，肿瘤分期为 cT1 期，肿瘤分化程度较差。匹配后，58 例 BRCA1/2 基因突变携带者在年龄（p = 0.6）、cT（p = 0.9）、cN 分期（p = 0.7）和肿瘤分化程度（p＞0.9）方面与 116 例非携带者相似。在突变携带者中，BRCA1/2 的 pCR 率为 15.5%，BRCA1 为 38%（8/21），BRCA2 为 2.7%（1/37），而非携带者为 7.8%（9/116）（p＜0.001）。在 NAC 后，12 例 BRCA1 基因突变携带者中有 5 例（41.7%）转化为 pN0，27 例 BRCA2 基因突变携带者中有 10 例（37%），91 例非携带者中有 19 例（20.9%）（p = 0.3）。多变量分析显示，BRCA1 基因突变状态与更高的 pCR 几率相关，而非携带者状态的几率较低（比值比[OR]6.31；95%置信区间[CI]1.95-20.5；p = 0.002），而 BRCA2 基因突变状态则没有（OR 0.45；95% CI 0.02-2.67；p = 0.5）。
结论
本研究表明，HR+/HER2-乳腺癌的 BRCA1 基因突变携带者的 pCR 率高于散发性癌症患者，可能从化疗中获益更大。考虑使用 NAC 来降期这些患者。
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