Women with breast cancer may be receiving treatments that are discordant with guideline recommendations for genetic subtypes of disease, based on a retrospective analysis of more than 20,000 patients.
Radiotherapy and chemotherapy practices were particularly out of alignment with guidelines, reported lead author Allison W. Kurian, MD, of Stanford (Calif.) University, and colleagues.
“Integrating genetic testing into breast cancer care has been complex and challenging,” the investigators wrote in JAMA Oncology. “There is wide variability in which clinicians order testing and disclose results, in the clinical significance of results, and in how clinicians interpret results to patients.”
According to the investigators, while germline testing is on the rise, little is known about how these test results are translating to clinical care.
To learn more, the investigators evaluated data from 20,568 women with stage 0-III breast cancer who entered the Surveillance, Epidemiology, and End Results registries of Georgia and California between 2014 and 2016.
Three treatment types were evaluated: surgery (bilateral vs. unilateral mastectomy), radiotherapy after lumpectomy, and chemotherapy. Treatment selection was compared with test results for breast cancer–associated genes, such as BRCA1/2, TP53, PTEN, and others. Associations were then compared with guideline recommendations.
Data analysis suggested that many clinicians were correctly using genetic test results to guide surgical decisions. For example, almost two-thirds (61.7%) of women with a BRCA mutation underwent bilateral mastectomy, compared with one-quarter (24.3%) who were BRCA negative (odds ratio, 5.52). For other pathogenic variants, the rate of bilateral mastectomy was still elevated, albeit to a lesser degree (OR, 2.41).
Generally, these practices align with recommendations, the investigators wrote, noting that research supports bilateral mastectomy with BRCA1/2, TP53, and PTEN variants, while data are lacking for other genetic subtypes.
Radiotherapy and chemotherapy practices were more discordant with guidelines. For example, women with a BRCA mutation were 78% less likely to receive radiotherapy after lumpectomy (OR, 0.22) and 76% more likely to receive chemotherapy for early-stage, hormone-positive disease (OR, 1.76). According to investigators, these findings suggest possible trends in undertreatment and overtreatment, respectively.
“We believe more research is needed to confirm our results and to evaluate long-term outcomes of pathogenic variant carriers to understand treatment decision making and consequences,” the investigators concluded.
The study was funded by the National Institutes of Health and the California Department of Public Health. The investigators reported relationships with Myriad Genetics, Genomic Health, Roche, and other companies.
SOURCE: Kurian AW et al. JAMA Oncol. 2020 Feb 6. doi: 10.1001/jamaoncol.2019.6400.