# Male Breast Cancer in Serbia: A 33-Year Retrospective Cohort Study of Genetic Predisposition, Clinicopathological Features, and Survival Outcomes

## TL;DR

This study examines male breast cancer in Serbia over 33 years, finding hormone-sensitive tumors and moderate survival rates with few genetic mutations.

## Contribution

The study provides a comprehensive 33-year retrospective analysis of male breast cancer in Serbia, including clinicopathological features, treatment patterns, and survival outcomes.

## Key findings

- Most patients had hormone-sensitive tumors with high estrogen and progesterone receptor positivity.
- Only 7 out of 37 genetically tested patients had pathogenic variants in BRCA1, BRCA2, CHEK2, or PALB2.
- Median overall survival was 131 months with moderate long-term survival rates observed.

## Abstract

Male breast cancer is a very rare type of malignancy, and little is known about its causes, characteristics, and long-term outcomes. This study analyzed 191 patients diagnosed with breast cancer in Serbia over 33 years to better understand the features of the disease, treatment approaches, genetic risk factors, and survival outcomes. We found that most patients had hormone-sensitive tumors, only a few carried inherited genetic mutations, and survival rates were moderate over the long term. By providing detailed information on the clinical and genetic aspects of male breast cancer, this research can help doctors make more informed decisions about diagnosis and treatment. It also provides valuable data for future studies, helping the research community improve the understanding and management of this uncommon disease.

Background/Objectives: Male breast cancer (MBC) is rare, accounting for less than 1% of all breast cancers. Given its low incidence, male breast cancer (MBC) remains understudied; this 33-year Serbian cohort was assessed for clinicopathological features, therapeutic approaches, genetic alterations, and survival. Methods: We retrospectively analyzed MBC patients diagnosed between 1991 and 2024 at the Institute for Oncology and Radiology of Serbia. Data included demographics, tumor characteristics, and stage, treatment, hormone receptor and HER2 status, Ki-67 index, genetic testing, and survival. Results: A total of 191 patients were identified (median age 66). Family history was negative in 91% and positive in 5.8%. T2 tumors were most frequent (36%), and 96% presented without metastasis. Mastectomy with axillary or sentinel lymph node dissection was performed in 78.5%. Neoadjuvant chemotherapy and radiotherapy were administered in 5.8% and 8.4%. Estrogen receptor positivity was 72%, progesterone receptor 88%, HER2 overexpression 11.0%, and triple-negative tumors 2.6% (40% with axillary involvement). High Ki-67 (≥15%) was recorded in 28.8%. Adjuvant chemotherapy, radiotherapy, and hormone therapy were given in 36%, 58%, and 68%. Among 37 genetically tested patients, seven had pathogenic variants (BRCA1, BRCA2, CHEK2, PALB2). Disease recurrence occurred in 30%. Median follow-up was 53 months. Median disease-free survival (DFS) was 82 months (1-, 2-, 5-, 10-year DFS: 87%, 73%, 57%, 39%). Median overall survival (OS) 131 months (1-, 2-, 5-, 10-year OS: 95%, 93%, 73%, 53%). Conclusions: This long-term cohort highlights the predominance of hormone-receptor positivity, the infrequency of germline mutations, and moderate survival rates, informing patient management and guiding future studies.