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Breast Cancer Polygenic Risk Score Can Help Predict Risk of Contralateral Disease

This story has been updated to correct Marjanka Schmidt's academic affiliation.

NEW YORK – A polygenic risk score for breast cancer can not only identify individuals at increased risk of developing primary breast cancer but also those carrying a higher risk of developing contralateral breast cancer, according to a new study.

About four percent of breast cancer patients develop contralateral breast cancer within 10 years of their initial diagnosis, though patients' risk varies. Previous studies have found that polygenic risk scores can stratify an individual's risk of primary breast cancer. An international team of researchers has now examined whether such scores can also uncover patients at increased risk of contralateral breast cancer.

Using data collected on thousands of individuals by the Breast Cancer Association Consortium, the team found that a polygenic risk score drawing on more than 300 different variants could predict contralateral breast cancer risk among women of European ancestry and, to a slightly weaker degree, women of Asian ancestry. As they reported in the American Journal of Human Genetics on Monday, the researchers found that adding this information to other risk factors could improve predictions.

"More accurate risk prediction will help identify women at high [contralateral breast cancer] risk who will benefit from additional surveillance and/or risk reducing mastectomy, and equally important, to identify those women at low risk in order to avoid unnecessary surgeries," Marjanka Schmidt from the Netherlands Cancer Institute and her colleagues wrote in the paper.

The researchers evaluated the association between two previously developed polygenic risk scores — PRS313 and PRS77 — and contralateral breast cancer within a Breast Cancer Association Consortium cohort. This cohort included 56,068 women of European ancestry who were diagnosed with invasive breast cancer, of whom 1,027 later developed contralateral breast cancer. 

They found that the hazard ratio for contralateral breast cancer per standard deviation of PRS313 was 1.25, and, by comparison, 1.21 for PRS77. In particular, women in the 90th to 100th percentile had a 1.38-fold risk of CBC, as compared with women in the 40th to 60th percentile.

From this, they estimated that women in the 10th percentile of PRS313 had 12.4 percent risk of developing contralateral breast cancer by the age of 80, while those in the 90th percentile had a 20.5 percent risk.

Meanwhile, in a study of 81,000 women with unilateral breast cancer, 3,607 women with contralateral breast cancer, and 62,830 women without breast cancer, they found that the odds ratio for contralateral breast cancer per standard deviation of PRS313 was 1.30, as compared to unilateral breast cancer, while the odds ratio for unilateral breast cancer per standard deviation of PRS313 was 1.82, as compared to control women.

When they focused on women of Asian ancestry within their cohort, they found a weaker odds ratio of 1.15 for contralateral breast cancer per standard deviation of PRS313. This weaker association could be due to the development of the risk score within a European population. Larger studies of Asian women and women of other ancestral backgrounds are needed to validate these findings and to generate population-specific risk scores, the researchers noted.

They found no evidence that the association between PRS313 and contralateral breast cancer risk was confounded by family history, adjuvant therapy, age, or other factors. This suggested to them that PRS313 is an independent risk factor for contralateral breast cancer and could be combined with other risk factors to provide an improved picture of risk.

"In conclusion, PRS313 is an independent factor associated with [contralateral breast cancer] risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies," the researchers wrote.