Senarathne, Wijendra

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.

Abstract Introduction: Breast metastases from non-mammary carcinomas are very rare and the molecular characteristics of these metastases have not been studied. Due to the uniqueness of this type of metastases, we evaluated whether there was any molecular or immunologic similarities among the patients with metastases to the breast. Patients and Methods: Fifty-one patients with metastatic carcinomas to the breast (49 female and 2 male) were identified in the files of Caris Life Sciences (Phoenix, AZ). Average age at presentation was 57 years (range, 20-90 years). Immunohistochemistry for PD-L1 was performed using SP142 (Ventana) or 22c3 (DAKO) antibodies; 592 genes sequencing (n=47), DNA microsatellite instability (MSI) (n=6) and total mutational burden (TMB) (n=14) were obtained from a next generation sequencing platform (Illumina). Results: Three most common primary sites were lung (19, 37%), ovary (15, 29%) and fallopian tubes/peritoneum (7, 14%). Ten metastases (20%) demonstrated neuroendocrine differentiation. When 1% cutoff was applied, tumor cells PD-L1 expression was detected in 10 cases (20%), and immune cells expression of PD-L1 in 19 patients (37%). Three cases (6%) had PD-L1 staining in both cancer and infiltrating immune cells. 50% of the cases exhibited mutations in TP53 gene, while other mutated genes followed the pathways typically seen in their primary sites (e.g. VHL in renal carcinomas, BRCA1 in fallopian tube carcinoma). Total mutational burden was high (≥10 mutations/Mb) in five out of 14 successfully analyzed cases (36%) and no case (0%) exhibited high microsatellite instability. Interestingly, estrogen receptor status was positive in 13/49 patients (26.5%) including 12 adenocarcinomas originating from ovary, Fallopian tube or peritoneum and one duodenal neuroendocrine. No tumor was HER2 positive. Conclusions: Metastases to the breast proved to be heterogeneous but there were molecular, endocrine and immunologic findings that yielded information that could be used to make therapeutic decisions which including the use of new immunotherapeutic strategies. Citation Format: Gatalica Z, Senarathne W, Vranic S, Pockaj BA. Profiling of metastatic carcinomas to the breast for the biomarkers of immuno-oncology therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-10-27.