Supplemental Digital Content is available in the text. The breast is a rare site for metastases, and their molecular characteristics have not been studied yet. Intrinsic molecular genetics, cancer characteristics, and breast tissue immune responses in diverse metastases to the breast have not been previously studied. We identified 64 patients with cancers metastatic to the breast: 51 carcinomas and 13 melanomas. Programmed death ligand 1 (PD-L1), steroid receptors, and HER2/neu expressions were evaluated using immunohistochemistry. Gene sequencing, copy number alterations, microsatellite instability, and tumor mutational burden were performed using next-generation sequencing platforms. The 3 most common primary sites for metastatic carcinomas were lung (37%), ovary (29%), and fallopian tubes/peritoneum (14%). TP53 mutations were commonly (50%) observed among the carcinoma cases, while other mutations were characteristic for the primary cancers (VHL in renal, BRCA1 in the fallopian tube, and BRAF in melanomas). High tumor mutational burden was detected in 5/14 carcinomas and 3/7 melanomas. Tumor cell PD-L1 expression was detected in 6 carcinomas, but not in any of the melanomas, whereas immune cells’ expression of PD-L1 was seen in 17 carcinomas and 6 melanomas. Estrogen receptor status was positive in 13/49 carcinomas including 12 adenocarcinomas originating from the ovary and fallopian tube or peritoneum and 1 duodenal neuroendocrine carcinoma. No carcinoma was HER2/neu positive. Intrinsic genetic characteristics of the metastases to the breast followed the pattern commonly seen in primary tumors. Biomarkers of potential benefit to immune checkpoint inhibition therapy were limited to PD-L1-positive non–small cell lung cancer. No common characteristics of the heterogeneous group of tumor metastases to this organ were identified.

中文翻译：

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乳腺癌转移癌靶向治疗和免疫肿瘤学的生物标志物

补充数字内容在文本中可用。乳房是罕见的转移部位，其分子特征尚未得到研究。先前尚未研究过多种乳腺转移中的内在分子遗传学、癌症特征和乳腺组织反应。我们确定了 64 名癌症转移到乳房的患者：51 名癌和 13 名黑色素瘤。使用免疫组织化学评估程序性死亡配体 1 (PD-L1)、类固醇受体和 HER2/neu 表达。使用下一代测序平台进行基因测序、拷贝数改变、微卫星不稳定性和肿瘤突变负荷。转移癌最常见的 3 个原发部位是肺 (37%)、卵巢 (29%) 和输卵管/腹膜 (14%)。TP53 突变在癌症病例中常见（50%），而其他突变是原发性癌症的特征（肾脏中的 VHL、输卵管中的 BRCA1 和黑色素瘤中的 BRAF）。在 5/14 癌和 3/7 黑色素瘤中检测到高肿瘤突变负荷。在 6 种癌中检测到肿瘤细胞 PD-L1 表达，但在任何黑色素瘤中均未检测到，而在 17 种癌和 6 种黑色素瘤中观察到免疫细胞表达 PD-L1。雌激素受体状态在 13/49 癌中呈阳性，包括 12 例源自卵巢和输卵管或腹膜的腺癌和 1 例十二指肠神经内分泌癌。没有癌是 HER2/neu 阳性的。乳腺转移瘤的内在遗传特征遵循原发性肿瘤中常见的模式。对免疫检查点抑制疗法有潜在益处的生物标志物仅限于 PD-L1 阳性非小细胞肺癌。没有鉴定到该器官的异质性肿瘤转移组的共同特征。