Early Genetic Testing Linked to Bilateral Mastectomy in Young BRCA Carriers with Breast Cancer

In women with young-onset breast cancer who carry a pathogenic BRCA1/2 mutation, receipt of early genetic testing was closely associated with bilateral mastectomy, according to an international study published in JAMA Network.

Background

Young women with breast cancer who have the BRCA1 or BRCA2 mutation face numerous concerns. They may have worries about the many years ahead of them with future cancer risk. Some may be interested in future fertility or preserving the option for breastfeeding. The BRCA BCY Collaboration is an international, retrospective cohort study network that came together to better understand the management of this population and what could be done to improve their care.

“While risk-reducing mastectomy has not been shown to improve survival among the general population or older BRCA carriers with breast cancer, the data show that bilateral mastectomy does offer survival advantages for BRCA mutation carriers with young-onset disease,” says Breast Medical Oncologist Halle Moore, MD. “For this study, we looked into the surgical choices of BRCA mutation carriers with young-onset breast cancer as well as the factors associated with type of surgery, whether it was a lumpectomy, mastectomy or bilateral mastectomy.”

Study details

Conducted at 109 centers across five continents, this study gathered data about women with a germline pathogenic or likely pathogenic variant in BRCA1/2 who were diagnosed at age 40 or younger with invasive stage 1-3 breast cancer between January 1, 2000 and December 31, 2020.

The study included 4,715 patients. Of these patients,

• 1,805 underwent breast-conserving surgery
• 1,752 underwent unilateral mastectomy
• 1,158 underwent bilateral mastectomy

Study findings

The strongest correlate of the choice of bilateral mastectomy was knowing the genetic mutation status at the time of diagnosis. Patients who knew this information at the time of surgical decision-making were much more likely to choose bilateral mastectomy. All patients in the data set had genetic testing but those who knew their status later were less likely to undertake this risk-reducing surgery.

Performing genetic testing in patients with early-onset breast cancer is concordant with NCCN guidelines, though the guidelines don’t specify the timing of testing. This study provides evidence for early testing.

“One of the biggest surprises to me of the study was that less than 10% of patients with young-onset breast cancer had genetic testing results available at the time of their surgical decision-making,” says Dr. Moore. “That’s far too low. We need to increase education, since the results of genetic testing will influence surgical decisions and potentially systemic treatment choices.”

In some centers like Cleveland Clinic, genetic testing can be done in parallel with surgical planning to avoid treatment delays. Dr. Moore notes that it’s also essential for those with a strong family history of breast cancer or a known mutation in their family to get genetic testing, even if they don’t have a breast cancer diagnosis.

Additional findings

Over the 20-year period studied, the use of bilateral mastectomies increased. The higher rates may be attributed to various factors, including heightened awareness about risk reduction options as well as improved options for immediate reconstructive surgery. There was significant variation in the rates of bilateral mastectomy by region. The highest rates (55.6%) were in North America with lower rates (17.3%) in Asia and Africa. Understanding these variations is quite complex, and may be due to many facets of care, such as differences in resources, payer systems, guidelines as well as cultural factors.

“Bilateral mastectomy isn’t the right option for everyone,” says Dr. Moore. “For those who are caring for patients with breast cancer, it is important for patients diagnosed at a young age to be offered genetic testing right away. Getting that information as soon as we can is going to empower the patient to make better decisions for herself.”

What’s next

With this vast patient data set, researchers are poised to conduct additional studies to better understand surgical interventions. In the meantime, more work is needed to best facilitate broad access to genetic testing for those with early-onset breast cancer and those at risk of it.