Study: Family History Increases Cancer Risk in BRCA-Tested Patients

Women who test negative for BRCA gene mutations may still be at greater risk of developing breast cancer than the general population, according to a study led by Cedars-Sinai Health Sciences University investigators. The findings, published in JAMA Network Open, highlight how strongly family history contributes to cancer risk.

An average woman has about a 13% chance of developing breast cancer during her lifetime, according to the National Cancer Institute. A BRCA1 or BRCA2 gene mutation raises breast cancer risk to 30%-70%, and BRCA testing is recommended for women with personal or family history of certain cancers, a known BRCA mutation in the family, or Ashkenazi Jewish ancestry.

"While most women who undergo genetic testing do not test positive for a cancer-risk-increasing BRCA mutation, they have generally been referred for testing because of strong personal or family cancer history," said Fahima Dossa, MD, PhD, surgical oncologist at Cedars-Sinai Cancer and lead author of the study. "Future cancer risk for these women has not been well studied, and our findings are the first to calculate that risk so that we can better guide all women who undergo BRCA testing."

Looking at the health records of almost 16,000 women who underwent BRCA testing in Ontario, Canada, from 2007 to 2016, investigators found that women who tested negative for a BRCA gene mutation still had a 25% lifetime risk of developing breast cancer.

And lifetime risk for those with a variant of unknown significance, which means little is known about that particular variant, was 30%, according to the findings.

Each patient's individual risk for breast cancer was substantially affected by their family history. Among women who tested positive for a BRCA mutation, breast cancer risk varied from roughly 56% to 86%, depending on the number of immediate family members who had breast or ovarian cancer, the study found.

"Based on these findings, a physician might recommend more frequent mammograms or breast MRI to a BRCA-positive patient in their 50s or 60s with no family history of breast cancer, but suggest preventive mastectomy as an option for a young BRCA patient with several cases of breast cancer in the family," Dossa said.

Dossa said that the only women in the study with the same breast cancer risk as the general population were those who had family history of cancer and a known BRCA mutation in the family, and were tested for that specific mutation but did not have the mutation.

"This study is a reminder to patients about the importance of having discussions with their doctors about genetic test results," Dossa said. "We finally have some data to help inform those conversations."

In July, Cedars-Sinai opened the Cedars-Sinai Cayton BRCA Center to provide coordinated screening, guidance and treatment to patients with BRCA mutations.

"Our leading-edge research supports our efforts to care for and improve outcomes for these patients," said Robert Figlin, MD, interim director of Cedars-Sinai Cancer. "Connecting science with cancer care is at the heart of what we do."

Other study authors include Kelly Metcalfe, RN, PhD; Zharmaine Ante, MSc; Ning Liu, PhD; Jordan Lerner-Ellis, PhD; Andrea Eisen, MD; and Nancy N. Baxter, MD, PhD.

Funding: This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health (MOH) and the Ministry of Long-Term Care (MLTC). This study also received funding from the Canadian Cancer Society (grant #315358). This work was also supported by the Canadian Institutes of Health Research (CIHR) grant funding no #148470.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.