Researchers have uncovered distinct alterations in the tumor genome of male patients with breast cancer that may suggest potential therapeutic targets, according to a recent study published by Assaad et al in Modern Pathology.
Background
Breast cancer in male patients represents less than 1% of all breast cancer cases per year. However, most male patients are unaware of their risk of breast cancer and are consequently diagnosed at more advanced stages compared with female patients. 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.
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.
Study Methods and Results
In a whole-genome sequencing analysis, the researchers examined the complete DNA landscape of the tumor samples from 10 male patients with breast cancer.
They 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 BRCA2 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.
Conclusions
The researchers highlighted that their new findings may represent a significant step in viewing breast cancer in male patients as a unique disease.
The researchers 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.
While larger studies may be needed to confirm the recent findings, the researchers suggested that tailoring treatments in this understudied male patient population will be necessary to effectively treat breast cancer.
Disclosure: For full disclosures of the study authors, visit modernpathology.org.
