Genetic testing results may reduce likelihood of guideline-concordant breast cancer treatment

In In The News by Barbara Jacoby

By: Allison W. Kurian


Women with breast cancer who tested positive for certain genetic mutations appeared more likely to receive distinct treatments, according to results of a population-based cohort study published in JAMA Oncology.

“These treatment patterns may be less concordant with practice guidelines, particularly for radiotherapy and chemotherapy,” Allison W. Kurian, MD, MSc, associate professor of medicine and health research and policy at Stanford University School of Medicine, told Healio. “Specifically, there may be more use of bilateral mastectomy and chemotherapy and less use of radiotherapy after breast-conserving surgery. This raises concern about the potential health outcomes that may result from such care.”

Germline genetic testing after breast cancer diagnosis has rapidly increased in recent years. However, little is known about the potential link between the results of genetic testing and subsequent treatment patterns.

To assess this possible association, Kurian and colleagues pooled data from SEER registries of Georgia and California on 20,568 women (mean age, 51.4 years) diagnosed with stage 0 to stage III breast cancer between 2014 and 2016. All women underwent germline genetic testing within 3 months after a breast cancer diagnosis and had more than 1 year of follow-up data available for review.

Researchers examined tumor characteristics to assess the standard guideline-recommended treatment options for each woman. They then evaluated the actual treatments received by women who tested positive for BRCA1 or BRCA2 mutations, those who tested positive for other pathogenic variants associated with breast cancer, including ATM, CDH1, CHEK2, NBN, NF1, PALB2, PTEN and TP53, and those who tested negative for these variants or had a variant not known to increase breast cancer risk.

Overall, 15,126 women were eligible for unilateral breast surgery, 7,248 for post-lumpectomy radiation therapy and 8,509 for possible omission of chemotherapy.

Researchers found BRCA1 or BRCA2 pathogenic variant carriers appeared more likely than those who tested negative for pathogenic variants to undergo bilateral mastectomy for a unilateral tumor (61.7% vs. 24.3%; OR = 5.52; 95% CI, 4.73-6.44), less likely to undergo post-lumpectomy radiotherapy (50.2% vs. 81.5%; OR = 0.22; 95% CI, 0.15-0.32) and more likely to receive chemotherapy for early-stage, ER/PR-positive breast cancer (38% vs. 30.3%; OR = 1.76; 95% CI, 1.31-2.34). Researchers observed similar patterns among women who carried pathogenic variants in other breast cancer-associated genes, but not among those with variants of undetermined significance.

Limitations of the study included difficulty in determining the exact start date of treatments using SEER data and the fact that the interval between diagnosis and testing was not statistically significant in multivariable models.

“We should be cautious about treating pathogenic variant carriers differently from other [patients with] breast cancer, unless evidence emerges to support doing so,” Kurian told Healio. “Future research will entail assessment of whether or not the observed departure from guidelines is associated with worse patient outcomes among pathogenic variant carriers.” – by Jennifer Southall

For more information:

Allison W. Kurian, MD, MSc, can be reached at Stanford University School of Medicine, 150 Governor’s Lane, HRP Redwood Bldg., Room T254A, Stanford, CA 94305; email:

Disclosures: The study was supported by grants from the NCI. Kurian reports research funding to her institution from Myriad Genetics. Please see the study for all other authors’ relevant financial disclosures.