Pathogenic variants tied to second primary breast cancer diagnosis risk for young survivors

Key takeaways:

• Five- and 10-year risks for second primary breast cancer were lower for women without vs. with pathogenic variants.
• Second primary breast cancer risk was higher for primary in situ vs. invasive breast cancer.

Breast cancer survivors aged 40 years or younger without pathogenic variants had a low second primary breast cancer diagnosis risk in the first 10 years after initial cancer diagnosis, researchers reported in JAMA Oncology.

“Given the increased availability of genetic testing for germline pathogenic variants that predispose young women to breast cancer, it is important to recognize that a heightened risk of second primary breast cancer may not apply to all young women,” Kristen D. Brantley, PhD, MPH, postdoctoral research fellow in the department of epidemiology at the Harvard T.H. Chan School of Public Health and the Dana-Farber Cancer Institute, and colleagues wrote. “There is a need to better classify young patients with breast cancer by their risk of developing second primary breast cancer to inform treatment decisions and surveillance options.”

Brantley and colleagues conducted a cohort study with data from 685 women (mean age at primary diagnosis, 36 years) who were enrolled in the Young Women’s Breast Cancer Study, a prospective study of women aged 40 years or younger with stage 0 to III breast cancer from August 2006 to June 2015. All women in the analysis underwent unilateral mastectomy or lumpectomy as primary breast cancer surgery. Using patient surveys and medical record reviews, researchers obtained data on demographics, genetic testing, treatment and outcomes.

Primary outcome was 5- and 10-year cumulative second primary breast cancer incidence.

During a median follow-up period of 10 years, 2.5% of women had a second primary breast cancer diagnosis. Median time from primary to second primary breast cancer diagnosis was 4.2 years. In the overall cohort, 5-year cumulative incidence of a second primary breast cancer diagnosis was 1.5% and 10-year cumulative incidence was 2.6%.

Overall, 577 women underwent genetic testing. Five- and 10-year cumulative risks for a second primary breast cancer diagnosis were lower among women without a pathogenic variant (1.3% and 2.2%, respectively) vs. women with pathogenic variants (5.5% and 8.9%, respectively).

In multivariate analysis, second primary breast cancer diagnosis risk was higher for women with pathogenic variants compared with women without (subdistribution HR = 5.27; 95% CI, 1.43-19.43) and for women with primary in situ vs. invasive breast cancer (subdistribution HR = 5.61; 95% CI, 1.52-20.7).

“While informative, the evidence from this study is not meant as the primary source for surgical decision-making, which should always consider the evolving literature as well as individual patient needs and risk factor profiles,” the researchers wrote. “It will be important to continue examining rates of second primary breast cancer among these young patients as they get further from primary diagnosis.”