Common genetic variants influence the risk of new breast tumor after breast cancer

The odds of developing a tumor in the second breast after breast cancer can be more accurately predicted through a risk score based on hundreds of common genetic variants, researchers of the Netherlands Cancer Institute show in their publication in the American Journal of Human Genetics. The researchers looked into the predictive value of the previously developed Polygenic Risk Score (PRS) in over 56,000 breast cancer patients.

Approximately 4% of breast cancer patients develop a second tumor in the other breast within 10 years after their first diagnosis. Researchers are eager to find the odds for each individual patient. "Patient with high risk scores can opt for a preventative mastectomy on the healthy breast, or come in for additional screenings," researcher Iris Kramer explains. "Patients with lower risk scores can feel more at ease. We can't underestimate how meaningful that can be."

313 genetic variants
To better assess the odds of breast tumors developing in the other breast, researchers make use of the Polygenic Risk Score (PRS). This risk model was developed in collaboration with other researchers in order to determine people's risk of developing a first breast tumor. Next to the well-known BRCA1/2 gene mutations, which significantly increase the risk of developing breast cancer, many other genetic variants can cause a much smaller increase in risk. Assessing all these varieties individually won't render any useful results, but prior research has shown that a combined risk score based on all 313 genetic variants, the PRS313 can be helpful in predicting the risks of developing breast cancer.

Predictability
The researchers tested their PRS313 against a dataset of more than 56,0000 European breast cancer patients, made available by the Breast Cancer Association Consortium. Patients were tracked for more than eight years. As it turned out, the PRS313 also predicted whether breast cancer patients would develop a tumor in the other breast. These predictions were not as accurate as those for a first tumor, however. "We found a hazard ratio per standard deviation of 1.25," Kramer explains. "To bring our research to the clinic, we created a model that can estimate the risk of developing a second tumor in the other breast before the age of 80. The 10% with the lowest PRS313 turned out to have a 12% risk, against 20% for the 10% of patients with the highest PRS313." The PRS313 may be able to predict the risks for women of Asian descent.

In combination with other risk factors
The difference in odds of developing breast cancer in the second breast between the high and low risk groups is minor. "We intend to use the PRS313 model in combination with with other risk factors such as age, family history, other genetic markers, and treatment of the first tumor," prof. dr. Marjanka Schmidt (NKI) explains. "This may help us create a more precise prediction model." Scientists are currently working on the development of a new, combined risk model. All PRS313 results will need to be validated through the use of an independent dataset. "We want to be able to estimate the risks of developing a new breast tumor, which will allow us to develop a personalized plan for each patient," says Schmidt.