Gene mutation boosts breast cancer risk contralaterally

Women with breast cancer before age 55 who carry an inherited mutation in the breast cancer susceptibility genes BRCA1 or BRCA2 are four times more likely to develop cancer in the breast opposite, or contralateral, to their initial tumor as compared to breast cancer patients without these genetic defects. These findings, by the Public Health Sciences Division’s Dr. Kathi Malone and colleagues, were published online April 5 in the Journal of Clinical Oncology.

Compared to non-carriers, breast cancer patients with a BRCA1 mutation had a 4.5-fold increased risk and those with a BRCA2 mutation had a 3.4-fold increased risk of a subsequent contralateral breast cancer, the researchers found. Carriers of either mutation who were diagnosed with breast cancer before age 55 faced an 18 percent cumulative probability of developing cancer in the opposite breast within 10 years as compared to a 5 percent cumulative probability among women who were mutation-free.

Factor: Age at initial diagnosis

In addition, the study revealed that among those who harbored a BRCA1 mutation, the younger they were at the time of initial diagnosis the higher was their risk of developing contralateral breast cancer. For example, mutation carriers diagnosed initially in their early to mid 30s had a 31 percent cumulative probability of developing contralateral breast cancer within 10 years as compared to a 7 percent probability among non-carriers.

“For young women with breast cancer, our results reinforce the message that early-onset disease is much more likely to be associated with a BRCA mutation,” said Malone, a breast cancer epidemiologist and the paper’s first author.

While only about 5 percent of breast cancer patients across all age groups carry a BRCA mutation, the younger a woman is at the time of her first breast cancer diagnosis, the more likely she is to have such a mutation. “In the youngest patients in our study— those with a first cancer diagnosed before age 35—we found that 16 percent of those with one breast tumor and 54 percent of those who had developed two primary breast cancers carried a mutation,” Malone said. Mutation frequencies were elevated also in women diagnosed with a first cancer between ages 34 and 44; among those initially diagnosed with one breast tumor the mutation frequency was 6.3; those diagnosed with two primary breast cancers had a mutation rate of 22 percent.

Importance of genetic testing

“These elevated mutation frequencies and risks for contralateral breast cancer associated with these mutations underscore the need for women diagnosed with a first breast cancer at a young age—regardless of family history—to consider genetic testing and to discuss it with their health care providers,” Malone said. “If they are found to carry a mutation in either of the BRCA genes, they should consider strategies for treatment, prevention and heightened surveillance in relation to their increased risk of a subsequent breast cancer diagnosis.”

This international, multicenter study (coordinated by Memorial Sloan Kettering Cancer Center) analyzed data from 705 women with contralateral breast cancer and a comparison group of 1,398 women with unilateral breast cancer. All of the women had been first diagnosed before age 55.

“This is the first and largest population-based study to date of these two important breast cancer susceptibility genes and their relation to contralateral breast cancer risk,” Malone said. “This study provides the clearest picture yet of the prevalence and risk of contralateral breast cancer among women in the general population who carry mutations in BRCA1 and BRCA2.”

Grants from the National Cancer Institute funded the study, which was conducted in collaboration with researchers from City of Hope; the Danish Cancer Society; Lund University (Sweden); Memorial Sloan-Kettering Cancer Center; the University of California, Irvine; the University of Iowa; the University of Southern California; the University of Virginia; and Vanderbilt University.