Breast cancer survival and tumor characteristics in premenopausal women carrying the CHEK2*1100delC germline mutation.

PURPOSE

Women carrying a CHEK21100delC germline mutation have an increased risk of developing breast cancer. This study aims to determine the proportion of CHEK21100delC carriers in a premenopausal breast cancer population, unselected for family history of breast cancer, and to investigate tumor characteristics and disease outcome with sufficient follow-up.

PATIENTS AND METHODS

We identified a retrospective cohort of 1,479 patients, who received surgery for invasive breast cancer between 1970 and 1994. All patients were diagnosed before age 50. Paraffin-embedded tissue blocks were collected for DNA isolation (normal tissue), subsequent CHEK2*1100delC analysis, and tumor revision. Median follow-up was 10.1 years.

RESULTS

We detected a CHEK21100delC germline mutation in 54 patients (3.7%). Tumor characteristics of CHEK21100delC carriers did not differ significantly from those of noncarriers. CHEK21100delC carriers had a two-fold increased risk (hazard ratio [HR], 2.1; 95% CI, 1.0 to 4.3; P = .049) of developing a second breast cancer and they had worse recurrence-free survival (HR, 1.7; 95% CI, 1.2 to 2.4; P = .006) and worse breast cancer-specific survival (HR, 1.4; 95% CI, 1.0 to 2.1; P = .072) compared with noncarriers. The poorer disease outcome of CHEK21100delC carriers could not be explained by the increased risk of second breast cancer.

CONCLUSION

Our study, which is representative for the premenopausal breast cancer population, reveals approximately 4% CHEK2*1100delC carriers have an increased risk of second breast cancer and a worse long-term recurrence-free survival rate. Their identification at time of diagnosis and prolonged intensive follow-up should be considered to optimize clinical management.