Voutsadakis Ioannis A
Algoma District Cancer Program, Sault Area Hospital, Sault Ste. Marie, ON P6B 0A8, Canada.
Section of Internal Medicine, Division of Clinical Sciences, Northern Ontario School of Medicine, Sudbury, ON P3E 2C6, Canada.
J Clin Med. 2022 Mar 14;11(6):1605. doi: 10.3390/jcm11061605.
Tumor mutation burden (TMB) is arising as a useful marker of checkpoint inhibitors' effectiveness in cancer patients in general and has been proposed as predictive in breast cancers. Despite the initial success of checkpoint inhibitors in triple-negative breast cancer, ER-positive breast cancers are less amenable to immunotherapy treatments due to the lower immunogenicity of this subset, associated with lower TMB and less pronounced inflammatory cell infiltration. However, a minority of ER-positive breast cancers do have a higher TMB and could be targets of immune checkpoint inhibitors.
This investigation uses publicly available genomic data to examine ER-positive/HER2-negative or luminal breast cancers with high mutation numbers and compare them with cancers of the same subtype and low mutation numbers. Clinical characteristics and molecular correlates according to mutation numbers are described.
ER-positive/HER2-negative and luminal breast cancers with high mutation numbers have a higher prevalence of mutations and in some of the series examined mutations in and . A significant proportion of cancers with high mutation numbers carry mutations in microsatellite instability genes and genes involved in DNA damage response. Despite these differences, the prognosis of ER-positive/HER2-negative and luminal breast cancers with high mutation numbers is not significantly different compared to counterparts with lower mutation counts.
These data may inform the potential suitability of these cancers for immunotherapy and could guide the development of rational combination therapies based on immune checkpoint inhibitors with other targeted drugs.
肿瘤突变负荷（TMB）正逐渐成为一种衡量检查点抑制剂对癌症患者总体疗效的有用标志物，并已被提议用于预测乳腺癌。尽管检查点抑制剂在三阴性乳腺癌中取得了初步成功，但雌激素受体（ER）阳性乳腺癌由于该亚组免疫原性较低，与较低的TMB和不太明显的炎症细胞浸润相关，因此对免疫治疗的反应较差。然而，少数ER阳性乳腺癌确实具有较高的TMB，可能成为免疫检查点抑制剂的靶点。
本研究使用公开可用的基因组数据来检查具有高突变数的ER阳性/人表皮生长因子受体2（HER2）阴性或管腔型乳腺癌，并将其与相同亚型且低突变数的癌症进行比较。描述了根据突变数的临床特征和分子相关性。
具有高突变数的ER阳性/HER2阴性和管腔型乳腺癌具有更高的突变发生率，并且在一些检测系列中存在特定基因的突变。相当一部分高突变数的癌症携带微卫星不稳定性基因和参与DNA损伤反应的基因突变。尽管存在这些差异，但与低突变数的对应癌症相比，具有高突变数的ER阳性/HER2阴性和管腔型乳腺癌的预后并无显著差异。
这些数据可能为这些癌症对免疫治疗的潜在适用性提供信息，并可指导基于免疫检查点抑制剂与其他靶向药物的合理联合治疗方案的开发。
