The Third Department of Breast Cancer, China Tianjin Breast Cancer Prevention, Treatment and Research Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Huanhu West Road, Hexi District, Tianjin, China.
Department of Breast Surgical Oncology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa District, Tokyo, Japan.
Sci Rep. 2020 Dec 3;10(1):21173. doi: 10.1038/s41598-020-78016-8.
BRCAness is defined as a phenotypic copy of germline BRCA mutations, which describes presence of homologous recombination defects in sporadic cancers. We detected BRCAness by multiplex ligation-dependent probe amplification (MLPA) and explored whether BRCAness can be used as a predictor of prognosis. BRCAness status was classified for total 121 breast cancer patients. Forty-eight patients (39.7%) were identified as BRCAness positive. Tumors of BRCAness were more likely to be hormone receptors negative (95.8% vs. 50.7%, P < 0.001), nuclear grade III (76.1% vs. 48.4%, P = 0.001) and triple-negative breast cancer subtype (91.6% vs. 42.5%, P < 0.001). Five-year disease free survival (DFS) (54.0% vs. 88.0%, P < 0.001) and overall survival (OS) (76.3% vs. 93.1%, P = 0.002) were significantly lower in BRCAness patients. In neoadjuvant chemotherapy subgroup analysis, clinical response rate for taxane-based regimen was significantly lower in BRCAness patients (58.3% vs. 77.8%, P = 0.041). Cox regression multivariate analysis showed that BRCAness was the independent prognostic factor for DFS (HR 2.962, 95%CI 1.184-7.412, P = 0.020), but not for OS (HR 2.681, 95%CI 0.618-11.630, P = 0.188). BRCAness is associated with specific characteristics and may suggest resistance to taxane-based chemotherapy. BRCAness can be used as a negative prognostic indicator for breast cancer.
BRCA 样特征定义为种系 BRCA 突变的表型副本,描述散发性癌症中同源重组缺陷的存在。我们通过多重连接依赖性探针扩增(MLPA)检测 BRCA 样特征,并探索 BRCA 样特征是否可用作预后的预测指标。共对 121 例乳腺癌患者进行了 BRCA 样特征状态分类。48 例(39.7%)被确定为 BRCA 样特征阳性。BRCA 样特征肿瘤更可能为激素受体阴性(95.8%对 50.7%,P<0.001)、核分级为 III 级(76.1%对 48.4%,P=0.001)和三阴性乳腺癌亚型(91.6%对 42.5%,P<0.001)。BRCA 样特征患者的 5 年无病生存率(DFS)(54.0%对 88.0%,P<0.001)和总生存率(OS)(76.3%对 93.1%,P=0.002)显著降低。在新辅助化疗亚组分析中,基于紫杉烷的方案的临床缓解率在 BRCA 样特征患者中显著降低(58.3%对 77.8%,P=0.041)。Cox 回归多因素分析显示,BRCA 样特征是 DFS 的独立预后因素(HR 2.962,95%CI 1.184-7.412,P=0.020),但不是 OS 的独立预后因素(HR 2.681,95%CI 0.618-11.630,P=0.188)。BRCA 样特征与特定特征相关,可能提示对基于紫杉烷的化疗耐药。BRCA 样特征可用作乳腺癌的负预后指标。