In a study reported in the Journal of Clinical Oncology, Josephine M.N. Lopes Cardozo, MD, PhD, and colleagues found that a higher score on a polygenic risk score consisting of 313 common genetic variants (the PRS313) was generally associated with more favorable tumor characteristics in patients with invasive breast cancer—but not with improvement in survival outcomes.
As noted by the investigators, increasing PRS313 is associated with an increased risk of breast cancer and contralateral breast cancer.
Josephine M.N. Lopes Cardozo, MD, PhD
Study Details
The analysis included 98,397 patients of European ancestry and 12,920 of Asian ancestry from the Breast Cancer Association Consortium (BCAC) and 683 patients from the European MINDACT trial, which included assessment of a 70-gene signature. The BCAC cohort included a higher proportion of patients with larger tumors and positive lymph nodes than the MINDACT cohort; other tumor and treatment characteristics were similar in the two cohorts.
Key Findings
A higher PRS313 score was generally associated with more favorable tumor characteristics. In the BCAC, increasing PRS313 was associated with lower tumor grade, hormone receptor–positive status, and smaller tumor size; increasing score was also associated with a higher probability of node-positive disease and younger age at diagnosis. In MINDACT, a higher PRS313 was associated with a low-risk 70-gene signature score.
In European patients from the BCAC, increasing PRS313 assessed as a continuous variable was associated with better overall survival (hazard ratio [HR] per unit standard deviation [SD] = 0.96, 95% confidence interval [CI] = 0.94–0.97) and breast cancer–specific survival (HR per unit SD = 0.96, 95% CI = 0.94–0.98). However, the association no longer held after adjustment for clinicopathologic characteristics and treatment: adjusted hazard ratios per unit standard deviation were 1.01 (95% CI = 0.98–1.05) for overall survival and 1.02 (95% CI = 0.98–1.07) for disease-specific survival. It was observed that the associations were no longer significant after adjustment for only estrogen receptor status and tumor grade.
Associations of PRS313 with survival outcomes were also not significant after adjusted analysis in Asian patients from the BCAC or in MINDACT. Among Asian patients, adjusted hazard ratios per unit standard deviation were 0.96 (95% CI = 0.87–1.07) for overall survival and 0.93 (95% CI = 0.75–1.17) for breast cancer–specific survival. In MINDACT, adjusted hazard ratios per unit standard deviation were 0.91 (95% CI = 0.69–1.18) for overall survival and 1.01 (95% CI = 0.69–1.49) for disease-specific survival.
The investigators concluded, “An increased PRS313 is associated with favorable tumor characteristics but is not independently associated with prognosis. Thus, PRS313 has no role in the clinical management of primary breast cancer at the time of diagnosis. Nevertheless, breast cancer mortality rates will be higher for [patients] with higher PRS313, as increasing PRS313 is associated with an increased risk of disease. This information is crucial for modeling effective stratified screening programs.”
Marjanka K. Schmidt, PhD, of the Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Cancer Institute and others. For full disclosures of the study authors, visit ascopubs.org.
