Women who have cancer in one breast may be more likely to develop cancer in the opposite breast if they have specific genetic changes that predispose them to developing breast cancer, according to a study led by the Mayo Clinic Comprehensive Cancer Center. The study findings, published in the Journal of Clinical Oncology, will help personalize approaches to breast cancer screening and risk factors, according to the study authors.
The study used data from 15,104 prospectively followed women in the CARRIERS (Cancer Risk Estimates Related to Susceptibility) consortium. The researchers found that patients who carry a germline mutation of BRCA1, BRCA2 or CHEK2 have at least a two-fold increased risk of developing cancer in both breasts, known as contralateral breast cancer. In contrast, patients carrying germline ATM mutations did not have a significantly increased risk of contralateral breast cancer. Among PALB2 carriers, the risk of contralateral breast cancer was significantly increased only in patients with estrogen receptor-negative disease.
“These are the first population numbers for these three genes beyond BRCA1/2,” says Fergus Couch, PhD, a breast cancer researcher at the Mayo Clinic Comprehensive Cancer Center, Zbigniew and Anna M. Scheller Professor of Medical Research and principal investigator of the CARRIERS study. “It is also one of the largest studies to provide estimates of contralateral breast cancer risk by age at diagnosis, menopausal status, and race/ethnicity in germline mutation carriers.” Most breast cancer patients who carry germline mutations assume they are at high risk of developing cancer in the opposite breast, says co-author Siddhartha Yadav, MD, medical oncologist, Mayo Clinic Comprehensive Cancer Center. Although this is true for BRCA1/2 mutation carriers with breast cancer, the risk of contralateral breast cancer in carriers of a germline mutation in ATM, CHEK2, or PALB2 has not been previously determined. Even in BRCA1/2 carriers, a comprehensive assessment of the risk of contralateral breast cancer based on age, estrogen receptor status, menopausal status and the effect of treatment of the initial breast cancer has not been performed.
“The findings reveal important information that will aid in personalized risk assessment of contralateral breast cancer in our patients who are carriers of germline mutations,” says Dr Yadav. “This level of detail will help inform decisions among patients and their care teams about appropriate screening and steps to reduce the risk of contralateral breast cancer based on more accurate and individualized risk estimates.” Premenopausal women who carry germline mutations generally have a higher risk of contralateral breast cancer compared with women who are postmenopausal when diagnosed with breast cancer, researchers have found. The study found that among women with germline mutations in breast cancer predisposition genes, black and non-Hispanic white women have a similarly increased risk of contralateral breast cancer, suggesting that risk management strategies should be similar.
“Many women undergo a bilateral mastectomy to reduce the chance of a second breast cancer,” says Dr. Couch. “We now have data to work from when making decisions about removing the other breast, aggressive monitoring, or using preventative medications.” (NEITHER)
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