# Novel Insights into the Enigmatic Genetics of Male Breast Cancer in China

## TL;DR

This study explores the genetic basis of male breast cancer in China, identifying key mutations that could improve diagnosis and treatment.

## Contribution

The study is the first to investigate germline genomic alterations in male breast cancer among the Han Chinese population.

## Key findings

- 14.6% of MaBC cases had pathogenic BRCA1/2 or PALB2 mutations, with BRCA2 being the most common.
- Recurrent mutations in RAD50, DMD, ARSA, and ABCC6 were identified in MaBC patients.
- One patient had a BRCA1 c.4015G > T mutation, and another had a PALB2 c.481_482dupGA alteration.

## Abstract

Objectives: The molecular characterization of male breast cancer (MaBC) has long been understudied, primarily due to its rare occurrence. Clinical management of MaBC remains profoundly challenging, with current therapeutic strategies largely extrapolated from female breast cancer protocols. Methods: Through panel-based sequencing targeting BRCA1, BRCA2, and PALB2 variants, we delineated the genomic landscape of 96 MaBC cases. Subsequent whole-exome sequencing (WES) of 84 BRCA1/2- and PALB2-mutation-negative MaBC patients, compared against 4480 healthy controls, revealed compelling findings. Results: Pathogenic variants in BRCA1/2 and PALB2 were identified in 14.6% (14/96) of MaBC cases, with BRCA2 mutations predominating at 12.5% (n = 12). Notably, one patient harbored the BRCA1 c.4015G > T stop-gained mutation, while another exhibited the PALB2 c.481_482dupGA alteration. Our analysis further uncovered 170 pathogenic/likely pathogenic mutations, with RAD50, DMD, ARSA, and ABCC6 demonstrating recurrent mutations in MaBC. Conclusions: As the inaugural germline genomic investigation of MaBC in a Han Chinese population, this work reveals clinically actionable alterations with diagnostic and therapeutic implications. These discoveries not only advance our understanding of MaBC’s molecular architecture but also underscore the critical need for dedicated research into this malignancy.