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

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.

Case report: Successful treatment of a rare HER2-positive advanced breast squamous cell carcinoma

“…The majority of MpBC cases exhibit negative expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), resembling triple-negative breast cancer (TNBC) but with a worse prognosis than conventional TNBC (Narayan et al, 2023;Tan et al, 2023;Zheng et al, 2023). In recent Frontiers in Pharmacology frontiersin.org years, advancements in research technology have led to an enhanced understanding of this uncommon breast tumor, resulting in increased attention and the accumulation of relevant treatment experience for MpBC (Qiu et al, 2022;Corso et al, 2023;Coutant et al, 2023;Kawachi et al, 2023). Herein, we report the initial case of a patient diagnosed with HER2-positive breast SCC, who achieved sustained tumor control through the utilization of HER2-targeted drugs in conjunction with paclitaxel.…”