HER2-Low Expression in Male Breast Cancer: Results from a Multicenter Series in Italy
Author:
Silvestri Valentina1ORCID, Valentini Virginia1ORCID, Bucalo Agostino1ORCID, Conti Giulia1ORCID, Manzella Livia2, Turchetti Daniela3, Russo Antonio4, Capalbo Carlo15ORCID, Ottini Laura1ORCID
Affiliation:
1. Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy 2. Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy 3. Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy 4. Section of Medical Oncology, Department of Surgical and Oncological Sciences, University of Palermo, 90127 Palermo, Italy 5. Medical Oncology Unit, Sant’Andrea University Hospital, 00189 Rome, Italy
Abstract
In the field of breast cancer care, a significant breakthrough has occurred with the recognition of HER2-low expression as a target for novel anti-HER2 antibody–drug conjugates (ADC). This discovery is reshaping the treatment landscape, challenging previous perceptions that considered HER2-low as clinically insignificant. The ability to target HER2-low expression is expected to have substantial clinical implications, irrespective of gender, including in cases of male breast cancer (MBC). However, an estimate of the prevalence of the HER2-low subtype in MBC is missing. This retrospective, observational, multicenter study was aimed at characterizing the HER2-low subtype in MBC. For the purpose of this study, the three-tiered categorization of HER2 (HER2-0, HER2-low, and HER2-positive) was used to reclassify the HER2-negative group into HER-0 or HER2-low subtypes. In the whole series of 144 invasive MBCs, 79 (54.9%) were HER2-0 (IHC scores of 0), 39 (27.1%) HER2-low (IHC scores of 1+/2+ with negative ISH), and 26 (18.0%) HER2-positive (IHC scores of 3+/2+ with positive ISH). Specifically, among hormone receptor-positive (HR+) HER2-negative invasive MBCs, 34.8% were HER2-low and 65.2% HER2-0. Compared with HER2-0, HER2-low subtype was associated with a positive lymph node involvement (p = 0.01). Other pathologic characteristics including histology, staging, and grading did not show notable variations between the two subtypes. The presence of germline BRCA1/2 pathogenic variants (PVs) did not significantly differ between HER2-0 and HER2-low MBCs. However, about 13% of HER2-low MBCs had germline PVs in BRCA1/2 genes, mainly BRCA2, a clinically relevant observation in the context of combined target therapy. Overall, our data, which focused on the largest gender-specific breast cancer series, to our knowledge, confirm that the emerging three-tiered categorization of HER2 (HER2-0, HER2-low, and HER2-positive) can also be considered in MBC, to mitigate both the gender gap and the underrepresentation of males in clinical trials.
Subject
Cancer Research,Oncology
Reference35 articles.
1. Navigating the HER2-Low Paradigm in Breast Oncology: New Standards, Future Horizons;Tarantino;Cancer Discov.,2022 2. DESTINY-Breast04 Trial Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer;Modi;N. Engl. J. Med.,2022 3. HER2-Low Breast Cancer: Where Are We?;Molinelli;Breast Care,2022 4. HER2-Low Breast Cancer: Pathological and Clinical Landscape;Tarantino;J. Clin. Oncol.,2020 5. Park, W.K., Nam, S.J., Kim, S.W., Lee, J.E., Yu, J., Ryu, J.M., and Chae, B.J. (2023). The Impact of HER2-Low Expression on Oncologic Outcomes in Hormone Receptor-Positive Breast Cancer. Cancers, 15.
|
|