Department of VIP Medical Services, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Curr Cancer Drug Targets. 2022;22(6):530-536. doi: 10.2174/1568009622666220214092207.
Metastatic triple-negative breast cancer (mTNBC) has a poor prognosis and few effective targeted therapy options. Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, has been granted accelerated approval by FDA for patients with deleterious BRCA-mutated human epidermal growth factor receptor 2 (HER2)-negative advanced/metastatic breast cancer. However, there is little data demonstrating that patients with particular forms of germline and/or somatic BRCA1/2, such as large fragment variation, can benefit from PARP inhibitors.
In 2011, a 40-year-old woman was diagnosed with TNBC having pT2N0M0 in the right breast, and a new irregular lesser tubercle in the left breast appeared after approximately 3 years, which was also diagnosed as TNBC. In 2017, computed tomography (CT) showed TNBC metastases to the lung and brain. A next-generation sequencing (NGS) was performed with a lung metastasis sample, and results showed a homologous recombination deficiency (HRD) score of 67, a germline large deletion of exon 2 in BRCA1, a novel somatic BRCA2-STARD13 rearrangement and copy number loss of RAD51. Since September 2017, the patient was treated with olaparib. Till the report date of this case, the patient underwent regular follow-up without disease recurrence.
To our knowledge, this is the first case describing a patient with lung- and brainmetastatic TNBC with combined germline and somatic large rearrangement and a high HRD score who achieved a long-term benefit from olaparib monotherapy. The use of NGS is promising in the treatment of TNBC in clinical practice.
转移性三阴性乳腺癌（mTNBC）预后差，有效的靶向治疗选择有限。奥拉帕利是一种聚（ADP-核糖）聚合酶（PARP）抑制剂，已被 FDA 加速批准用于携带有害 BRCA 突变的人表皮生长因子受体 2（HER2）阴性晚期/转移性乳腺癌患者。然而，几乎没有数据表明具有特定种系和/或体细胞 BRCA1/2 形式（如大片段变异）的患者可以从 PARP 抑制剂中获益。
2011 年，一名 40 岁女性被诊断为右乳 TNBC，pT2N0M0，大约 3 年后左乳出现新的不规则小结节，也被诊断为 TNBC。2017 年，计算机断层扫描（CT）显示 TNBC 转移到肺部和脑部。对肺部转移样本进行下一代测序（NGS），结果显示同源重组缺陷（HRD）评分 67，BRCA1 外显子 2 种系大片段缺失，BRCA2-STARD13 新的体细胞重排和 RAD51 拷贝数缺失。自 2017 年 9 月以来，患者接受奥拉帕利治疗。截至本病例报告日期，患者定期随访，无疾病复发。
据我们所知，这是首例描述携带种系和体细胞大片段重排且 HRD 评分高的肺脑转移性 TNBC 患者，长期接受奥拉帕利单药治疗获益的病例。NGS 的应用在 TNBC 的临床治疗中具有广阔的前景。
