Department of Breast Oncology and Surgery, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan.
Department of Pathology, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan.
J Surg Res. 2020 Jun;250:143-147. doi: 10.1016/j.jss.2019.12.047. Epub 2020 Feb 7.
A subgroup of triple-negative breast cancer (TNBC) shows impaired BRCA1 function owing to causes other than mutation, which is called "BRCAness." DNA-damaging agents are known to have more efficacy in BRCA1-mutant tumors than mitotic poisons. We conducted a prospective single-arm clinical trial of neoadjuvant chemotherapy (NAC) using an anthracycline-based regimen without taxanes for BRCAness TNBCs.
BRCAness was examined using the multiplex ligation-dependent probe amplification (MLPA) method in TNBC cases. For BRCAness cases, NAC was performed with anthracycline-based regimens without additional taxanes.
A total of 30 patients with TNBC were enrolled. MLPA was successfully performed in 25 patients. Eighteen patients (72%) showed BRCAness. Twenty-three patients received NAC as per the protocol. On analysis, the clinical response rate (complete response plus partial response) was 76.4%, and the pathological complete response rate was 35.3%.
The interim analysis revealed that the pathological complete response rate was lower than estimated. Therefore, BRCAness by MLPA was not sufficient to predict the therapeutic response to anthracycline-based regimens in TNBC.
三阴性乳腺癌(TNBC)的亚组表现出 BRCA1 功能障碍,其原因除了突变以外,还被称为“BRCAness”。已知 DNA 损伤剂在 BRCA1 突变型肿瘤中的疗效优于有丝分裂毒物。我们进行了一项新辅助化疗(NAC)的前瞻性单臂临床试验,该试验使用不含紫杉烷类药物的蒽环类方案治疗 BRCAness TNBC。
使用多重连接依赖性探针扩增(MLPA)方法检测 TNBC 病例中的 BRCAness。对于 BRCAness 病例,采用不含额外紫杉烷类药物的蒽环类方案进行 NAC。
共纳入 30 例 TNBC 患者。25 例患者成功进行了 MLPA。18 例(72%)患者表现出 BRCAness。23 例患者按照方案接受了 NAC。分析显示,临床缓解率(完全缓解加部分缓解)为 76.4%,病理完全缓解率为 35.3%。
中期分析显示,病理完全缓解率低于预期。因此,MLPA 检测到的 BRCAness 不足以预测 TNBC 对蒽环类方案的治疗反应。