||Weischer M, Nordestgaard BG, Pharoah P, Bolla MK, Nevanlinna H, Van't Veer LJ, Garcia-Closas M, Hopper JL, Hall P, Andrulis IL, Devilee P, Fasching PA, Anton-Culver H, Lambrechts D, Hooning M, Cox A, Giles GG, Burwinkel B, Lindblom A, Couch FJ, Mannermaa A, Grenaker Alnæs G, John EM, Dörk T, Flyger H, Dunning AM, Wang Q, Muranen TA, van Hien R, Figueroa J, Southey MC, Czene K, Knight JA, Tollenaar RA, Beckmann MW, Ziogas A, Christiaens MR, Collée JM, Reed MW, Severi G, Marme F, Margolin S, Olson JE, Kosma VM, Kristensen VN, Miron A, Bogdanova N, Shah M, Blomqvist C, Broeks A, Sherman M, Phillips KA, Li J, Liu J, Glendon G, Seynaeve C, Ekici AB, Leunen K, Kriege M, Cross SS, Baglietto L, Sohn C, Wang X, Kataja V, Børresen-Dale AL, Meyer A, Easton DF, Schmidt MK, Bojesen SE
||PURPOSE: We tested the hypotheses that CHEK2*1100delC heterozygosity is associated with increased risk of early death, breast cancer-specific death, and risk of a second breast cancer in women with a first breast cancer. PATIENTS AND METHODS: From 22 studies participating in the Breast Cancer Association Consortium, 25,571 white women with invasive breast cancer were genotyped for CHEK2*1100delC and observed for up to 20 years (median, 6.6 years). We examined risk of early death and breast cancer-specific death by estrogen receptor status and risk of a second breast cancer after a first breast cancer in prospective studies. RESULTS: CHEK2*1100delC heterozygosity was found in 459 patients (1.8%). In women with estrogen receptor-positive breast cancer, multifactorially adjusted hazard ratios for heterozygotes versus noncarriers were 1.43 (95% CI, 1.12 to 1.82; log-rank P = .004) for early death and 1.63 (95% CI, 1.24 to 2.15; log-rank P < .001) for breast cancer-specific death. In all women, hazard ratio for a second breast cancer was 2.77 (95% CI, 2.00 to 3.83; log-rank P < .001) increasing to 3.52 (95% CI, 2.35 to 5.27; log-rank P < .001) in women with estrogen receptor-positive first breast cancer only. CONCLUSION: Among women with estrogen receptor-positive breast cancer, CHEK2*1100delC heterozygosity was associated with a 1.4-fold risk of early death, a 1.6-fold risk of breast cancer-specific death, and a 3.5-fold risk of a second breast cancer. This is one of the few examples of a genetic factor that influences long-term prognosis being documented in an extensive series of women with breast cancer.