Profiling of metastatic cancers to the breast for the biomarkers of immuno-oncology therapy


Zoran Gatalica, Wijendra Senarathne, Kelsey Poorman, Semir Vranic, Barbara A. Pockaj


In the present study, we reviewed a large cohort (n=64) of cancers metastatic to breast profiled at a single reference center (Caris Life Sciences, Phoenix, AZ) for detected biomarkers of targeted and immuno-oncologic therapies.


Female or male breast is a rare organ for non-mammary cancers to metastasize to, and molecular characteristics of these metastases have not been yet studied. We investigated molecular and immune characteristics of diverse types of metastases to the breast, in order to gain knowledge of potential therapy options.

We identified 64 patients with metastatic cancers to the breast: 51 carcinomas and 13 melanomas. PD-L1 expression was evaluated using SP142 (Ventana) (n=41), 22c3 (DAKO) (n=10) and 28-8 (DAKO) (n=13) antibodies. Gene sequencing was done using two different panels: 592-gene [n=19]; and 44-gene [n=41]). Copy number alterations (n=17), microsatellite instability (MSI) and tumor mutational burden (TMB) (n=19) were performed using next generation sequencing platforms (Illumina).

Three most common primary sites for metastatic carcinomas to the breasts were lung (37%), ovary (29%) and fallopian tubes/peritoneum (14%). Carcinomas of an unknown primary site (CUP) were rare (n=2) while melanomas of unknown primary (MUP) were common (n=10/13). Mutations in TP53 gene were commonly (50%) observed among the carcinoma cases, while other mutated genes were characteristic for the primary tumor type (e.g. VHL in renal clear cell carcinomas, BRCA1 in fallopian tube carcinoma, SMARCB1 in renal medullary carcinoma and BRAF in melanomas). High TMB (≥10 mutations/Mb) was detected in five of 14 analyzed carcinomas (the highest TMB was 29/mb and was detected in a CUP case) and in three of seven analyzed melanomas, (two were MUP). No case exhibited MSI. Tumor cells (TC) PD-L1 expression was detected in six carcinomas but not in any of the melanoma, while immune cells (IC) expression of PD-L1 was seen in 17 carcinomas and 6 melanomas.

Metastases to the breast proved to be heterogeneous and biomarkers of potential benefit to approved immuneoncology therapy were limited to PD-L1 positive NSCLC, while targeted therapy biomarkers followed the pattern commonly seen in primary tumors.


  • We confirm the rarity of secondary cancers to the breast (1.4% of all breast biopsies with a malignancy).
  • The study also showed heterogeneity in terms of biomarkers of potential benefit to I-O and targeted therapies, necessitating individual patient profiling.

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