BRCA mutation increases breast cancer risk in opposite breast

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 Fred Hutchinson Cancer Research Center breast cancer epidemiologist Kathleen Malone, Ph.D., 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.

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, first author of the paper and a member of the Public Health Sciences Division at the Hutchinson Center.

This is the first population-based study of these two important breast cancer susceptibility genes and their relation to contralateral breast cancer risk,” Malone said. It is also the largest study to date of the association between BRCA mutations and contralateral breast cancer. “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.

More than 180,000 U.S. women are diagnosed with breast cancer annually. “With growing numbers of breast cancer survivors nationwide, the magnitude of the burden associated with the potential risk of second primary contralateral breast cancer is quite large,” Malone said.

BRCA1 and BRCA2 belong to a class of genes known as tumor suppressors. These genes help ensure genetic integrity of the cell and help prevent uncontrolled cell growth that can lead to cancer. Mutation of these genes has been linked to the development of hereditary breast and ovarian cancer.

Source: Fred Hutchinson Cancer Research Center, USA



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