Study Identifies Most Important Genetic Factors in Breast Cancer Risk

A new, large-scale study has identified the most important genetic factors in a person’s breast cancer risk. The study was conducted by 250 researchers from institutions and universities in more than 25 countries.

The study, which was published on January 20 in the New England Journal of Medicine, analyzed data from more than 113,000 women—some who had breast cancer and some without the disease. The researchers specifically looked at 34 genes that are thought to raise a woman’s risk of breast cancer. The risk of developing breast cancer is partially linked with genetics, but figuring out exactly which genes increase the risk is still being explored.

After studying the data, the researchers pared down the list of genes that can raise breast cancer risk to nine. Those include:

• ATM
• BRCA1
• BRCA2
• CHEK2
• PALB2
• BARD1
• RAD51C
• RAD51D
• TP53

The importance of each gene varies depending on the type of cancer someone may have. Variations in five genes—ATM, BRCA1, BRCA2, CHEK2, and PALB2—were linked with a higher overall risk of developing breast cancer, while variants in ATM and CHEK2 were more likely to indicate a risk for estrogen receptor-positive breast cancers.

“The results of this study define the genes that are most clinically useful for inclusion on panels for the prediction of breast cancer risk, as well as provide estimates of the risks associated with protein-truncating variants, to guide genetic counseling,” the researchers concluded.

Breast Cancer Risk

Breast cancer is the most common cancer for women in the U.S., behind skin cancers, according to the American Cancer Society. The average risk of developing breast cancer for a woman in the U.S. is 13%—or a one in eight chance.

While anyone, regardless of gender, can develop breast cancer, there are certain factors that put someone at greater risk of developing the disease, including:

• Getting older
• Having certain genetic mutations
• Getting menstrual periods before age 12 and starting menopause after age 55
• Having dense breasts
• A personal history of breast cancer or certain non-cancerous breast diseases
• A family history of breast or ovarian cancer
• A previous treatment using radiation therapy
• Having previously taken the drug diethylstilbestrol (DES)

Impact on Genetic Testing

This study “basically confirms what we already know,” Banu Arun, MD, a professor in the Department of Breast Medical Oncology at The University of Texas MD Anderson Cancer Center in Houston, tells Verywell.

Doctors already test for these genes when screening patients for breast cancer risk, Arun says. However, she points out, the findings may help doctors home in on how many genes they test for. “I’m hoping this will clarify that maybe there are 50 genes out there that we can test for, but we don’t have to test for all 50,” she says.

The study also underscores that certain BRCA gene mutations have a higher risk for developing cancer, Arun says, adding, “this study and others can help give relative risks, so you can determine the significance of someone’s results based on that.”

If you do happen to test positive for one of these genes or genetic variants, Arun says you shouldn’t panic. “The ordering physician or genetic counselor will discuss next steps with you,” she says. “There are recommendations and best practices to help.”