Germline pathogenic variants in metaplastic breast cancer patients: a monocentric study and literature review

Abstract

Abstract Metaplastic breast cancer (MpBC) is a rare, aggressive type of breast cancer, often classified as triple negative (TN). Scarce information is available about germline testing in MpBC. We retrospectively reviewed MpBC patients counseled at our Institute and found to harbor germline pathogenic variants (PVs), and we revised literature data. We identified a germline PV in 15 MpBC patients: 13 in BRCA1 (86.7%), one in TP53 (6.7%), one in MLH1 (6.7%) genes. Eight MpBC PV carriers in BRCA1 have been previously described, including a patient with a PV in both BRCA1 and TP53. MpBC histological subtype in PV carriers was heterogeneous. All MpBCs were TN but 13.3% in our series showed HER2 overexpression. We described the largest series of MpBCs with germline PVs. As previously reported, we observed that BRCA1 is the mainly involved gene in MpBC patients who underwent germline testing according to specific selection criteria. Additional studies on unselected patients are required to assess the authentic role of germline BRCA1 PVs in MpBCs and to explore the possible involvement of other genes in MpBC predisposition. Unraveling a specific MpBC molecular landscape is a starting point for the definition of new therapeutic strategies, since these tumors have a poor prognosis.