Study Identifies Novel Therapeutic Targets for Males With Breast Cancer

By: Joshua D. Madera, MD
Posted: Wednesday, March 20, 2024

Given the low incidence of males diagnosed with breast cancer and the limited insight into the genetic variations associated with their disease, the optimal management strategy for these patients remains elusive. According to a study published in Modern Pathology, whole-genome sequencing has revealed genetic markers that may be suitable treatment targets. Additional investigative efforts are warranted to establish treatment guidelines for this patient population, suggested Juan Miguel Mosquera, MD, MSc, Professor of Pathology and Laboratory Medicine and Director of Research Pathology at the Englander Institute for Precision Medicine at Weill Cornell Medicine, New York, and colleagues.

“Our study is the first whole-genome sequencing characterization of male breast cancer, which uncovered potentially relevant variants, including structural events in cancer genes, homologous recombination deficiency signatures, and germline pathogenic mutations,” explained the study authors.

A total of 28 male patients with breast carcinoma were recruited for the study. Tumor samples were stained with hematoxylin and eosin, and whole-genome sequencing was performed (n = 10). Patients had moderately differentiated intraductal carcinoma (n = 7) or poorly differentiated carcinoma (n = 3). In addition, expression of FGFR1 was measured using fluorescence in situ hybridization in all patients.

The study authors identified mutations in important driver genes including ARID2, FAT1, GATA3, and SMARCA4. In addition, analysis of cancer-associated genes revealed structural variations in ARID1A, ESR1, GATA3, NF1, and NTRK1. Evidence of homologous recombination deficiency was identified in two patients, both of which contained deleterious variants of BRCA2. Furthermore, 21% of cases showed evidence of FGFR1 amplification.