Polygenic risk scores may predict risk for second breast cancer

Polygenic risk scores appeared to predict contralateral breast cancer among survivors who harbored BRCA1 and BRCA2 mutations, according to findings presented at the European Breast Cancer Conference.

“Our research suggests that [polygenic risk scores] can also be used to help patients who have survived their first breast cancer to better understand their level of risk for a second breast cancer,” Alexandra van den Broek, PhD, of the Netherlands Cancer Institute in Amsterdam, said in a press release. “We hope these findings will add to the existing knowledge about predicting risk for a second breast cancer in these survivors.”

Survivors who also harbor a BRCA1 or BRCA2 mutation are at increased risk for contralateral breast cancer. However, research has shown wide variation in the risks.

Previous research identified low-risk variants that influence risk for breast cancer in the general population, and it has been reported that polygenic risk scores may be highly predictive of the risk for breast cancer.

“Women with a BRCA mutation are more likely to develop breast cancer when they are young and, unfortunately, some will be unlucky and go on to suffer a second breast cancer later in life,” van den Broek said. “We know these women are at a higher risk, but it has also been shown that individual risks may vary widely, so we wanted to see if there was any way to better identify patients at lower and higher risks.”

van den Broek and colleagues evaluated data from more than 10,000 mutations carriers (BRCA1, n = 6,614; BRCA2, n = 4,372) from the Consortium of Investigators of Modifiers of BRCA1/2, a large international cohort of reported mutation carriers.

Researchers genotyped the mutations with the iCOGS Infinium assay (Illumina; 10%) or OncoArray (Illumina; 90%) then performed Kaplan Meier curves and Cox regression analyses to determine any associations between different polygenic risk scores and contralateral breast cancer risk scores.

Preliminary results showed polygenic risk score to be associated with risk for contralateral breast cancer among both BRCA1 and BRCA2 carriers.

The polygenic risk score developed specifically for BRCA1 mutations carriers and for those most at risk for a first ER-negative breast cancer in the general population appeared most predictive of contralateral breast cancer risk among BRCA1 carriers. The HR for highest vs. lowest quartile was 1.33 (95% CI, 1.14-1.54) with the BRCA1 polygenic risk score and 1.47 (95% CI, 1.26-1.72) for the ER-negative polygenic risk score.

The polygenic risk score developed specifically for BRCA2 mutations carriers (HR for highest vs. lowest quartile = 1.47; 95% CI, 1.19-1.83) and those most at risk for a first ER-positive breast cancer in the general population (HR for highest vs. lowest quartile = 1.38; 95% CI, 1.11-1.71) also appeared predictive of contralateral breast cancer risk among BRCA2 carriers.

Researchers observed contralateral breast cancer risks differences of approximately 20% at 20 years between the lowest and highest quartile of the polygenic risk scores with the best predictions.

Further analyses are needed to explore the interaction with other predicting factors, including treatment and age.

“Eventually, the best predicting polygenic risk score should be incorporated in risk prediction tools to contribute to optimizing personalized prevention and early detection strategies after breast cancer for these high-risk women,” the researchers wrote. – by Melinda Stevens

Reference:

van den Broek A, et al. Abstract 7. Presented at: European Breast Cancer Conference; March 18-20, 2018; Barcelona, Spain.

Disclosures: The authors report no relevant financial disclosures.