Department of Pathology, Guangdong Provincial People's Hospital, Guangzhou, China.
Department of Pathology, Mayo Clinic, Rochester, MN, USA.
Diagn Pathol. 2020 May 11;15(1):50. doi: 10.1186/s13000-020-00971-7.
Immunotherapy has demonstrated encouraging clinical benefits in patients with advanced breast carcinomas and Programmed death ligand 1 (PD-L1) expression has been proposed as an immunotherapy biomarker. Challenges with current PD-L1 testing exist and tumor mutation burden (TMB) is emerging as a biomarker to predict clinical response to immunotherapy in melanoma and non-small cell lung cancer patients. However, TMB has not been well characterized in breast carcinomas.
The study cohort included 62 advanced breast cancer patients (13 primary and 49 metastatic). Genetic alterations and TMB were determined by FoundationOne CDx next generation sequencing (NGS) and the association with clinicopathologic features was analyzed.
High TMB was observed in a relatively low frequency (3/62, 4.8%). TMB levels were positively associated tumor infiltrating lymphocytes and significantly higher TMB was observed in breast carcinomas with DNA damage repair gene mutation(s). There was no significant association between TMB levels and other analyzed clinicopathologic characteristics.
Our data indicate the importance of DNA damage repair proteins in maintaining DNA integrity and immune reaction and breast carcinoma patients with DDR mutation may benefit from immunotherapy.
免疫疗法在晚期乳腺癌患者中显示出令人鼓舞的临床获益，程序性死亡配体 1（PD-L1）表达已被提议作为免疫疗法的生物标志物。目前 PD-L1 检测存在挑战，肿瘤突变负担（TMB）作为预测黑色素瘤和非小细胞肺癌患者对免疫治疗临床反应的生物标志物正在出现。然而，TMB 在乳腺癌中的特征尚未得到很好的描述。
该研究队列包括 62 例晚期乳腺癌患者（13 例原发性和 49 例转移性）。通过 FoundationOne CDx 下一代测序（NGS）确定遗传改变和 TMB，并分析其与临床病理特征的关联。
高 TMB 的发生率相对较低（3/62，4.8%）。TMB 水平与肿瘤浸润淋巴细胞呈正相关，并且在具有 DNA 损伤修复基因突变的乳腺癌中观察到 TMB 水平显著更高。TMB 水平与其他分析的临床病理特征之间没有显著关联。
我们的数据表明 DNA 损伤修复蛋白在维持 DNA 完整性和免疫反应中的重要性，并且具有 DDR 突变的乳腺癌患者可能受益于免疫治疗。
