Incidence of BRCA1 somatic mutations and response to neoadjuvant chemotherapy in Chinese women with triple-negative breast cancer
Incidence of BRCA1 somatic mutations and response to neoadjuvant chemotherapy in Chinese women with triple-negative breast cancer
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中国三阴性乳腺癌女性BRCA1体细胞突变发生率及对新辅助化疗的反应
DOI：
10.1016/j.gene.2016.03.004
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发表时间：
2016
期刊：
影响因子：
3.5
通讯作者：
Xie Yuntao
中科院分区：
文献类型：
--
作者：
Li Manxiu;Zhang Juan;Ouyang Tao;Li Jinfeng;Wang Tianfeng;Fan Zhaoqing;Fan Tie;Lin Benyao;Xie Yuntao
BRCA1体细胞突变状态在三阴性乳腺癌(TNBC)中的流行情况尚未有很好的文献报道。本研究的目的是确定BRCA1体细胞突变的频率，并探讨BRCA1有害体细胞突变状态与新辅助化疗疗效之间的关系。其中112例患者在治疗前获得新鲜肿瘤组织，93例患者在手术后获得新鲜肿瘤组织。采用聚合酶链式反应-直接测序法检测肿瘤样本中BRCA1的体细胞突变。结果205例TNBC患者中，8例(3.9%)携带BRCA1致病体细胞突变。这8个BRCA1有害的体细胞突变包括5个移码或无义突变(c.191_212del22、c.1664delA、c.4674_4675c+c17del、c.3671_3672insTTCC、c.1162a)、一个剪接位点突变(c.134G+12T)和两个错义突变(c.5511G)和两个错义突变(c.5511G)。BRCA1有害体细胞突变携带者与非携带者的肿瘤特征无显著差异。在97例接受新辅助化疗的患者中，病理完全应答率为32.0%。BRCA1有害体细胞突变携带者(n=15)的PCR率高于非携带者(n=992)(60.0%vs30.4%，P=0.32)，但因样本量较小，差异无统计学意义。
BackgroundThe prevalence of BRCA1 somatic mutations status in triple-negative breast cancer (TNBC) has not been well documented. The aims of this study were to determine the frequency ofBRCA1somatic mutations and to investigate the association betweenBRCA1deleterious somatic mutation status and response to neoadjuvant chemotherapy in women with TNBC.MethodsTwo hundred and five TNBC patients withoutBRCA1germline mutations were enrolled in this study. Fresh tumor tissues were available for this cohort of 205 patients, including 112 patients with fresh core needle biopsy tumor tissues before treatment and 93 patients with fresh tumor tissues procured after surgery.BRCA1somatic mutations were determined in the tumor samples using PCR-direct sequencing assay. Among the 112 patients with core needle biopsy samples, 97 patients received neoadjuvant chemotherapy.ResultsEight patients (3.9%) carried aBRCA1pathogenic somatic mutation in this cohort of 205 TNBC patients. These eightBRCA1deleterious somatic mutations included five frameshift or nonsense mutations (c.191_212del22, c.1664delA, c.4674_4675 + 17del, c.3671_3672insTTCC, c.1162A > T), one splicing site mutation (c.134 + 2T > G) and two missense mutations (c.5511G > C and c.286G > A). No significant differences in tumor characteristics betweenBRCA1deleterious somatic mutation carriers and non-carriers were observed. The pCR (pathologic complete response) rate was 32.0% in the 97 patients who received neoadjuvant chemotherapy.BRCA1deleterious somatic mutation carriers (n = 5) had a higher pCR rate than did non-carriers (n = 92) (BRCA1carriers vs non-carriers, 60.0% vs 30.4%,P= 0.32), although it did not reach a significance due to a small sample size.ConclusionsA small subset of TNBC patients carried aBRCA1deleterious somatic mutation;BRCA1somatic mutation carriers are likely to respond to neoadjuvant chemotherapy.