March 2024 | George M. Pikler, M.D., Ph.D., FACP, Lead Oncology Advocate N1X10

Finding New Therapeutic Targets for Male Breast Cancer

Male breast cancer (MaBC) accounts for only 0.5% to 1% of all reported cases of breast cancer each year. Although a majority of the research on breast cancer has focused on female patients, the incidence of breast cancer in male patients has increased at a much faster rate than in female patients over the last 40 years. Most male patients are unaware of their risk of breast cancer and are consequently diagnosed at more advanced stages compared with female patients. And, unlike in female patients, survival rates in male patients with breast cancer haven’t significantly improved over the last 30 years, according to the National Cancer Institute.

The molecular characterization of male breast cancer (MaBC) has received limited attention in research, mostly because of its low incidence rate. Utilizing whole-genome sequencing (WGS) and state-of-the-art analyses, researchers at Weill Cornell Medicine have uncovered distinct alterations in the tumor genome of male patients with breast cancer that may suggest potential therapeutic targets. They examined the complete DNA landscape of the tumor samples from 10 male patients with breast cancer and discovered gene mutations and molecular profiles capable of impacting diagnosis and treatment. The researchers revealed that the mutations were in several genes known to drive cancer progression. They also identified structural variants impacting five other cancer-associated genes. Two of the patients had BRCA-2 mutations that impaired DNA repair, a common cause of breast cancer in female patients.

After evaluating the tumor samples of 18 additional male patients, the researchers found that about 21% of the tumors had 10 to 20 excess copies of the FGFR1 gene linked to treatment resistance in some female patients with breast cancer. They noted that FGFR1 amplification is already a therapeutic target.

The researchers highlighted that their new findings may represent a significant step in viewing breast cancer in male patients as a unique disease. They emphasized that breast cancer therapies are currently available to target the gene mutations identified in 80% (n = 8/10) of the male patients involved in the analysis, opening new pathways to treatment. For instance, immunotherapy and poly-ADP ribose polymerase inhibitors may be effective in patients with BRCA2-mutated breast cancer and a high number of tumor mutations. Cancer-triggering rearrangements in the NTRK1 gene may respond to drugs called kinase inhibitors. In addition, the gene mutations identified in the recent analysis may lead to the discovery of new targeted therapies in this patient population.

Modern Pathology. 2024, 37 (4)

Erica Cross, PA


Erica is a board certified Physician Assistant. She obtained her Master’s degree in Physician Assistant studies from Our Lady of the Lake College in Baton Rouge, LA. She began practicing in 2011 and has worked clinically in Orthopedics and Dermatology. The majority of her career has been spent in a Dermatology practice where she assisted in Mohs surgery, treating various types of skin cancer. She also teaches in the medical simulation department at the University of South Alabama and enjoys every aspect of medical education.