Although about one-third of women with BRCA-mutated breast cancer will develop contralateral breast cancer in 15 years, the risk is actually much higher for certain women, and they should be counseled accordingly, said Kelly Metcalfe, RN, PhD, of the University of Toronto, who led a multicenter study to identify relevant risk factors.¹

"Data suggest that women with a BRCA mutation have an increased risk of contralateral breast cancer, but we don't know whether there may be modifiers of this contralateral risk," Dr. Metcalfe said at the 2010 Breast Cancer Symposium.

The study found that age at diagnosis, strong family history of breast cancer, and oophorectomy significantly influenced the patient's risk for contralateral disease. The study population included 846 women (N = 669, plus 177 deceased) with stage I or II disease diagnosed by age 65 between 1975 and 2008. Of these women, 810 had an intact contralateral breast and were included in the analysis. Pedigrees were available for 801 women. A BRCA1 or BRCA2 mutation was identified in either the patient (88%) or a family member (12%).

The mean age at diagnosis was 42 years. Approximately half had undergone a unilateral mastectomy, and the other half underwent lumpectomy, usually with radiation therapy. No patient had a bilateral mastectomy.

Contralateral breast cancer was diagnosed in 18.4% at an average of 5.7 years after diagnosis. The 15-year actuarial risk was 33.8%, the 10-year risk was 22.0%, and the 5‑year risk was 13.1%. Risk was slightly higher for BRCA1 mutation carriers.

Risk Highest among Certain Groups

"Age was an important predictor," Dr. Metcalfe announced. "Women with a young age at onset were at significant risk."

For women aged 40 and younger at diagnosis, the risk of contralateral breast cancer was over 40% at 15 years, compared with approximately 35% for those aged 40 to 49 and 15% for those aged 50 or older (P = .001; see Fig. 1). Annually, this amounted to a 2.8% annual risk for the youngest group vs a 1.3% annual risk for those aged 50 and up.

The decision to undergo oophorectomy or not also significantly affected the patient's risk, as oophorectomy conveyed a 47% reduction in risk, primarily seen in the BRCA1 subset, she said.

Age at diagnosis was also important with regard to oophorectomy, as women younger than 50 with intact ovaries had a 60% 15-year risk, compared with 20% for those aged 50 and up when diagnosed (P = .0003). Women younger than 50 who underwent oophorectomy reduced their risk by 55%.

"Women with early-onset breast cancer have the highest risk and get the most protection from oophorectomy," Dr. Metcalfe concluded.

Family history was also a significant risk factor, especially when affected relatives were young at the time of diagnosis. For every first-degree relative with breast cancer under age 50, the risk of breast cancer rose 33% (P = .008). For women with two or more relatives with breast cancer under age 50, risk was increased by close to 80% compared to those with no affected relatives younger than 50 when diagnosed (P = .006).

Neither chemotherapy nor the use of tamoxifen was protective, overall or by mutation or age subgroup.

Identifying Those at Greatest Risk

Dr. Metcalfe emphasized how these risk factors can be used in counseling women. For example, while the 15-year risk for a woman diagnosed before age 50 is 37.6%, it greatly increases if she decides against oophorectomy and nearly doubles if she has two or more first-degree relatives diagnosed at a young age.

"These are the women we really need to identify and counsel appropriately about surgery to prevent contralateral breast cancer," she said. "Our strongest recommendation is to remove the breast, which can bring their risk down to almost zero."

Dr. Metcalfe and colleagues will be following this cohort to determine the impact of these factors on survival.
The Breast Cancer Symposium was cosponsored by the American Society of Breast Disease, The American Society of Breast Surgeons, ASCO, the American Society for Radiation Oncology, the National Consortium of Breast Centers, and The Society of Surgical Oncology. ■

Reference

1. Metcalfe KA, Lynch HT, Ghadirian P, et al: Predictors of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. 2010 Breast Cancer Symposium. Abstract 159. Presented October 1, 2010.