S4-2: The Risk of Contralateral Breast Cancer in BRCA1/2 Carriers Compared to Non-BRCA1/2 Carriers in an Unselected Cohort.
Authors: van den Broek AJ , Schmidt MK , Tollenaar RAEM , van't Veer LJ , van Leeuwen FE 
Published: June 2012

Background: Women who survived their first breast cancer have a higher risk to develop a new primary tumor in the contralateral breast than the risk of women in the general population to develop a first breast cancer. Especially women who carry a germline mutation in either the BRCA1 or the BRCA2 gene face a high lifetime risk of developing a synchronous or metachronous bilateral breast cancer. It is important to provide precise risk estimates of contralateral breast cancer and identify factors which predict the risk of CBC in this group of high risk women. To answer these questions, we looked at the effect of BRCA1/2-carriership and its interaction with other factors on the risk to develop a CBC in an unselected cohort of breast cancer patients. Materials and methods: We collected clinico-pathological, treatment and follow-up data for 4856 patients with unilateral, invasive breast cancer, diagnosed under the age of 50, between 1970 and 2003, in ten different hospitals throughout The Netherlands. Germline DNA was isolated from formalin-fixed paraffin-embedded tissue and patients were tested for the most prevalent pathogenic BRCA1 and BRCA2 mutations in The Netherlands. DNA and clinical data were coded before the analyses. All second primary breast tumors in the contralateral breast diagnosed more than 3 months after the diagnosis of the first breast cancer were considered as events. Preliminary results from life-table analysis and Cox Proportional Hazard models adjusted for age at diagnosis are shown here. Further statistical analyses will include competing risk analysis.

Results: In 4856 patients genotyped for BRCA1/2 mutations, 206 (4.2%) carriers were identified. During a median follow-up of 9.8 years (range 0–38), 9% of the patients developed a CBC, resulting in a cumulative 15-year risk for CBC of 10.4% (95% CI = 9.25−11.7) for non-carriers and 35.4% (95% CI = 25.9−46.9) for carriers of a BRCA1 or BRCA2 mutation (HR = 4.04 (95% CI = 2.88−5.68)). Patients carrying a BRCA1/2 mutation who were diagnosed under the age of 40 with their first breast cancer experienced a cumulative 15-year risk for CBC of 52.4% (95% CI = 36.4−70.3) versus 21.3% (95% CI = 12.0−36.0) in those over the age of 40 (HR = 0.30 (95% CI = 0.14−0.65)). Furthermore, BRCA1/2 mutation carriers with a triple negative first tumor had a cumulative risk for CBC of 43.6 (95% CI = 25.1−67.7), in contrast, BRCA1/2 mutation carriers with a non-triple negative first tumor had a cumulative risk for CBC of 13.4% (95% CI = 4.21−38.4) (HR = 0.24 (95% CI = 0.07−0.86)). Age at diagnosis and triple negative status were not found to be predictors of the risk of CBC in non-carriers (HR = 0.81 (95% CI = 0.53−1.24) and HR = 1.49 (95% CI = 0.91−2.41) respectively).

Discussion: In this study we identified subgroups of patients with a high risk to develop a CBC after their first breast cancer. Guidelines about treatment decisions and screening for follow-up should take into account these high risk subgroups to provide even better information and counseling for BRCA1/2 mutation carriers.

On behalf of more than 20 involved authors of the BOSOM study from 10 different hospitals and institutions throughout The Netherlands.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr S4-2.