Mutation quadruples repeat breast cancer risk

Younger breast cancer patients who have a mutation in the well-known BRCA1 or BRCA2 genes are four times as likely to get cancer in the other breast as most patients, researchers reported on Monday.

And the younger a woman was at her first diagnosis, the more likely she would have tumors in her other breast, the researchers found. That means testing for BRCA mutations is important in women under the age of 40 if they are diagnosed with breast cancer.

"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," Kathleen Malone of the Fred Hutchinson Cancer Research Center in Seattle, who led the study, said in a statement.

Writing in the Journal of Clinical Oncology, Malone and colleagues said they analyzed data from 705 women whose cancer had come back in the second breast and 1,398 women who just had cancer in one breast. All of the women had been first diagnosed before age 55.

Women with a mutation in the BRCA1 gene had 4.5 times the risk of having cancer in the second breast, and those with a BRCA2 mutation had 3.4 times the risk, compared to women without the mutations, they found.

Patients with either mutation who were diagnosed with breast cancer before age 55 had an 18 percent cumulative probability of developing cancer in the opposite breast within 10 years, compared to a 5 percent probability among breast cancer patients without those two mutations.

Women with BRCA1 mutations diagnosed in their early- to mid-30s had a 31 percent cumulative probability of having a tumor in the other breast within 10 years, while young women without the mutations had a 7 percent risk, Malone's team found.

The BRCA1 and BRCA2 genes are mutated in about 5 percent of breast cancer patients. But the younger a woman is when diagnosed, the more likely she is to have one of the mutations, the researchers said.

"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.

"Our study is the first to include the full spectrum of family history profiles, from minimal to extreme risk, and thus is likely to more accurately reflect the true risk of contralateral breast cancer among BRCA carriers in the general population," she said.

According to the American Cancer Society and the International Agency for Research on Cancer, 1.3 million new breast cancer cases are diagnosed annually and it kills 465,000 women a year, making it the leading global cancer killer of women.

SOURCE: http://jco.ascopubs.org/cgi/content/abstract/JCO.2009.24.2495v1 Journal of Clinical Oncology, online April 5, 2010.