Dutch Study Reveals High Contralateral Risk in BRCA Carriers

Younger Cancer Patients Have Greater Risk of Developing Cancer in Other Breast

Ron Zimmerman

December 12, 2011

December 12, 2011 (San Antonio, Texas) — The fact that women who survive a primary breast cancer have a higher risk of developing a second cancer in their other breast is well recognized. In a study presented here at the 34th Annual San Antonio Breast Cancer Symposium, Dutch investigators attempted to determine which subgroups might be more at risk, and precisely how much more at risk they might be.

Ms. van den Broek

Carriers of the BRCA1 or BRCA2 genetic mutation who had previous breast cancer were 3 times more likely to develop another primary cancer in the contralateral breast, according to the researchers. "We wanted to get a better insight into the precise factors that predict risk," lead author Alexandra J. van den Broek, MSc, from the Department of Psychosocial Research and Epidemiology at the Netherlands Cancer Institute in Amsterdam, told Medscape Medical News.

In the BOSOM (Breast Cancer Outcome Study of Mutation Carriers) study, 4856 women were diagnosed with unilateral invasive breast cancer before the age of 50 years in 10 Dutch hospitals from 1970 to 2003.

Among the eligible women, 206 (4.2%) carried the BRCA1 or BRCA2 mutation. The overall rate of occurrence of contralateral breast cancer was 9%. Median follow-up was 9.8 years. The overall 15-year risk of developing contralateral breast cancer was 10.4% for noncarriers of the mutation and 35.4% for carriers.

Subgroups of women with a high risk of developing second cancers in the other breast were identified; the subgroup of women who were mutation carriers and who had their first tumors detected at a relatively young age had the highest risk.

BRCA1 and BRCA2 carriers who had a first breast cancer diagnosis at 40 years of age or younger had a 15-year risk for contralateral breast cancer of 52.4%. Among BRCA1/2 carriers who were 40 to 50 years of age, the 15-year risk was 21.3%. Mutation carriers with a triple-negative first cancer had a 15-year risk of 43.6%. Among carriers with a nontriple-negative first cancer, the risk was 13.4%.

Among noncarriers of the mutation, age at diagnosis and triple-negative status were not predictors of the risk for contralateral breast cancer.

Ms. van den Broek explained to Medscape Medical News thatthe significance of this study "is that if our results are confirmed, we can find groups of affected patients early and implement guidelines for screening, counseling, or prophylactic measures, such as surgery or preventive chemo- or hormone therapy."

Dr. Kathy Miller

Kathy Miller, MD, assistant professor at Indiana University School of Medicine, Indianapolis, said that physicians already have an understanding that tumors in one breast means that the patient has a heightened risk for a second contralateral tumor.

"We've always known that the incidence is higher [for contralateral cancer] among women with a first cancer, but before, what we had to do for those patients harboring a [BRCA1 or BRCA2] mutation is extrapolate. This study gives us that information. The question is: If you've had a cancer that led you to genetic testing that identified your deleterious mutation, then what is your risk of developing a new breast cancer? This study gives those women the best information."

Dr. Miller believes the study is useful in her practice. "I would much rather have specific estimates from the [same] population of the woman that I'm talking to than have to extrapolate from a global population database. Based on the patient's age, this gives us more specific numbers for exactly that population. But it still really comes down to what these numbers and those risks mean...[to] an individual woman."

Dr. Miller doesn't think she's required to make a decision for her patient, but rather to present the best current information so that the patient can make her own informed decision.

"My job is to find the most reliable estimates of their risks of events and over time so they can make decisions about whether that risk is sufficiently high that they would proceed to prophylactic surgery," she said.

The bottom line for clinicians, Dr. Miller said, is that BOSOM puts epidemiologic numbers on a concept. "What this does is give us estimates specifically for women with mutation who have already had one cancer," she said, "so we don't have to do that extrapolation from the whole population."

The study authors and Dr. Miller have disclosed no relevant financial relationships.

34th Annual San Antonio Breast Cancer Symposium (SABCS): Abstract S4-2. Presented December 8, 2011.

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