Germline mutations in BRCA1 and BRCA2 account for approximately 2–3% of breast cancers while CHEK2*1100delC may account for an additional 0.7% 1. To date, several small studies have suggested a worse outcome of survival in BRCA1 and BRCA2 carriers. However, the evidence is inconsistent and most studies were subject to different types of bias. An increased risk for contralateral breast cancer, especially in interaction with radiotherapy, for CHEK2*1100delC carriers has been shown 2. Only one study has so far evaluated the impact of CHEK2*1100delC on survival, showing a worse disease-free survival compared with control breast cancer patients 3.

Our aim is to evaluate breast cancer survival and to determine risk estimations for the development of contralateral breast or ovarian cancer (as a second primary), as well as to evaluate tumour characteristics, in BRCA1/2 and CHEK2*1100delC carriers in an unselected, non-family based, retrospective cohort of breast cancer patients diagnosed under age 50. The cohort to be evaluated will include approximately 5000 patients, treated in several Dutch hospitals between 1973 and 1995. Tissue blocks from these patients are being obtained and, after coding, about 70 BRCA1/2 founder and recurrent mutations, representing approximately 72% of the Dutch BRCA1/2 mutations, and the CHEK*1100delC mutation are being determined. Data for 1700 patients from the Netherlands Cancer Institute and the Leiden University Medical Center are being completed. We have so far found, in 1255 samples, 4.1% BRCA1/2 carriers (41 BRCA1 and 11 BRCA2 mutations) and 3.8% CHEK2*1100delC, with no overlap among these groups. An interim analysis showed that BRCA1 tumours seem to have less favourable prognostic characteristics while BRCA carriers have an OR of 3 for contralateral breast cancer compared with the non-BRCA carriers. Genetic determinants of tumour characteristics, risk for contralateral breast cancer and survival of CHEK2*1100delC carriers will be presented.