Men ages 60 and under showed especially high rates of advanced disease staging. (© Pixel-Shot - stock.adobe.com)
StudyFinds’ Editor-in-Chief Steve Fink says he’s already taking necessary steps after testing positive for BRCA2 variant
For years, we’ve heard about the increased breast and ovarian cancer risks for women who carry mutations in the BRCA1 and BRCA2 genes. But what about men? A new review reveals that male BRCA carriers face significant – and often overlooked – cancer risks of their own.
Half of all people with BRCA mutations are men, yet they undergo genetic testing at just one-tenth the rate of women. This oversight means many men are unaware they carry a mutation that substantially increases their odds of developing aggressive prostate cancer, pancreatic cancer, and male breast cancer.
“Not enough men are getting genetic testing to see if they carry a BRCA1 or BRCA2 gene variant that increases their cancer risk,” explains lead author Dr. Heather Cheng, director of the Fred Hutch Prostate Cancer Genetics Clinic. “And the men who know they are carriers get tested for their daughters, but don’t always know why it’s important for their own health.”
The review, published in JAMA Oncology, highlights how our understanding of cancer risks in male BRCA carriers has evolved. For instance, men with BRCA2 mutations face up to an 8.6-fold increased risk of prostate cancer compared to non-carriers. Their lifetime risk may be as high as 60% – a stark contrast to the typical 12% lifetime risk for men in the general population.
Pancreatic cancer risk is also elevated, with BRCA2 carriers facing a 3- to 7.8-fold increased risk. While less common, male breast cancer risk shoots up dramatically for BRCA2 carriers, with a lifetime risk of up to 8.9% compared to 0.1% in the general male population.
These elevated risks mean male BRCA carriers may benefit from enhanced cancer screening. But without widespread genetic testing, most men remain in the dark about their mutation status and miss out on potentially life-saving early detection.
“After my mother recently tested positive for the BRCA2 gene mutation, I decided to get tested myself,” says StudyFinds Editor-in-Chief Steve Fink. “Thank goodness I did because I learned I was positive for the mutation too. My doctor educated me on all the increased risks and preventative care that I probably wouldn’t have thought about before. I’m scheduled to meet with a geneticist and will be as aggressive as I need to be to protect my health. And of course, it’s important that I tested for my kids too.”
The review also highlights how BRCA status can guide treatment decisions. For men diagnosed with prostate, pancreatic, or breast cancer, knowing they carry a BRCA mutation opens the door to targeted therapies like PARP inhibitors. These drugs have shown impressive results in clinical trials, sometimes doubling survival times compared to standard treatments.
Despite the clear benefits of identifying male BRCA carriers, significant barriers remain. Many physicians lack awareness about testing guidelines for men. There’s also a shortage of genetic counselors to help patients understand complex genetic information.
Cultural factors play a role too. There’s still a stigma around men discussing cancer risk, especially for cancers like breast cancer that are seen as “women’s diseases.” The authors call for increased education about male BRCA risks, both for healthcare providers and the general public.
“At first I laughed when my doctor suggested I begin regularly performing self-breast exams for abnormalities,” says Fink. “But it’s not a laughing matter: I’m at a much higher risk of developing male breast cancer, and it’s imperative I routinely check myself.”
Cheng stressed the need for males to be aware of their family history of cancer and to share this important information with their primary care providers throughout their lives. She also emphasized the importance of proper genetic testing: “Popular direct-to-consumer services, such as 23andMe and Ancestry, perform some genetic testing using DNA collected from saliva, but these services are not adequate for identifying the genetic variants most likely to increase cancer risks.”
The review refers to “males” as individuals assigned the male sex at birth and cites a study recommending that transgender women and gender neutral and gender fluid carriers of the BRCA1/2 mutations undergo individualized cancer screening based on sex-specific organs.
Cheng, who treats prostate cancer patients at the South Lake Union clinic at Fred Hutch, noted that programs such as the Fred Hutch Prostate Cancer Genetics Clinic, the GastrointestinaI Cancer Prevention Program and the Breast and Ovarian Cancer Prevention Clinic collaborate to provide comprehensive resources for both patients with cancer and their family members who may also carry increased inherited cancer risk.
“We have multiple programs centered around cancer genetics and prevention that help patients and their families,” Cheng said. “I get to meet the brothers and sons of my patients, some before they have cancer, in order to talk about screening for prostate cancer. And that’s really gratifying. It’s important for folks out there to know that we have these resources because sometimes they don’t know where to go for state-of-the art cancer early detection, prevention and treatment.”
“These are recent guideline changes,” Cheng stressed. “I personally hope that as more people, including males are screened, we can advance progress and research faster, find the people most impacted and work together to reduce the burden of BRCA1 and BRCA2-related cancers.”
As our understanding of BRCA-related cancers in men continues to grow, so too does the imperative to close the genetic testing gap. The health of countless men – and their families – may depend on it.
Paper Summary
Methodology
This paper was a comprehensive literature review, examining and synthesizing findings from numerous studies on BRCA mutations in men. The authors searched medical databases for relevant research, focusing on studies that assessed cancer risks, screening recommendations, and treatment implications for male BRCA carriers. They also reviewed current clinical guidelines from major medical organizations to assess how well they address male BRCA carriers.
Results
The review found that men with BRCA mutations, especially BRCA2, face significantly increased risks for certain cancers:
- Prostate cancer: Up to 8.6-fold increased risk for BRCA2 carriers, with lifetime risks as high as 60%
- Pancreatic cancer: 3- to 7.8-fold increased risk for BRCA2 carriers
- Male breast cancer: Lifetime risk up to 8.9% for BRCA2 carriers
The authors also found that male BRCA carriers are drastically undertested compared to women, with testing rates about one-tenth that of female carriers. Current screening guidelines for male carriers vary between organizations and are often buried within guidelines primarily focused on women.
Limitations
The authors note several limitations in the current body of research on male BRCA carriers:
- Many risk estimates come from studies with limited diversity, often focusing on populations of European or Ashkenazi Jewish ancestry
- Some studies may have selection bias, as they recruited participants based on family history of breast/ovarian cancer without considering other BRCA-associated cancers
- Long-term data on the effectiveness of enhanced screening protocols for male carriers is still limited
Discussion and Takeaways
The review emphasizes the need for increased awareness about BRCA-related cancer risks in men, both among healthcare providers and the general public. The authors argue for more inclusive genetic testing guidelines and improved access to genetic counseling. They also highlight how identifying male BRCA carriers can inform both cancer screening and treatment decisions, potentially improving outcomes.
The paper discusses ongoing clinical trials investigating novel screening approaches for male carriers, such as MRI-based prostate cancer screening. The authors encourage male BRCA carriers to participate in such trials when possible to help advance the field.
A key takeaway is the need for a shift in perspective – viewing BRCA mutations as a family health issue rather than primarily a women’s health concern. This shift could help normalize genetic testing for men and improve cascade testing within families.
Funding and Disclosures
This work was funded by the National Cancer Institute and U.S. Department of Defense. The authors acknowledge support from the BRCA Research and Cure Alliance and the Men & BRCA Program at the Basser Center for BRCA, as well as several government grants.
