CHEK2*1100delC heterozygosity in women with breast cancer associated with early death, breast cancer-specific death, and increased risk of a second breast cancer

Weischer, M.; Nordestgaard, B. G.; Pharoah, P.; Bolla, M. K.; Nevanlinna, H.; Van't Veer, L. J.; Garcia-Closas, M.; Hopper, J. L.; Hall, P.; Andrulis, I. L.; Devilee, P.; Fasching, P. A.; Anton-Culver, H.; Lambrechts, D.; Hooning, M.; Cox, A.; Giles, G. G.; Burwinkel, B.; Lindblom, A.; Couch, F. J.; Mannermaa, A.; Alnaes, G. G.; John, E. M.; Dork, T.; Flyger, H.; Dunning, A. M.; Wang, Q.; Muranen, T. A.; Van Hien, R.; Figueroa, J.; Southey, M. C.; Czene, K.; Knight, J. A.; Tollenaar, R. A. E. M.; Beckmann, M. W.; Ziogas, A.; Christiaens, M. -R.; Collee, J. M.; Reed, M. W. R.; Severi, G.; Marme, F.; Margolin, S.; Olson, J. E.; Kosma, V. -M.; Kristensen, V. N.; Miron, A.; Bogdanova, N.; Shah, M.; Blomqvist, C.; Broeks, A.; Sherman, M.; Phillips, K. -A.; Li, J.; Liu, J.; Glendon, G.; Seynaeve, C.; Ekici, A. B.; Leunen, K.; Kriege, M.; Cross, S. S.; Baglietto, L.; Sohn, C.; Wang, X.; Kataja, V.; Borresen-Dale, A. -L.; Meyer, A.; Easton, D. F.; Schmidt, M. K.; Bojesen, S. E.

doi:10.1200/JCO.2012.42.7336

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. © 2012 by American Society of Clinical Oncology.

CHEK2*1100delC heterozygosity in women with breast cancer associated with early death, breast cancer-specific death, and increased risk of a second breast cancer / Weischer M.; Nordestgaard B.G.; Pharoah P.; Bolla M.K.; Nevanlinna H.; Van't Veer L.J.; Garcia-Closas M.; Hopper J.L.; Hall P.; Andrulis I.L.; Devilee P.; Fasching P.A.; Anton-Culver H.; Lambrechts D.; Hooning M.; Cox A.; Giles G.G.; Burwinkel B.; Lindblom A.; Couch F.J.; Mannermaa A.; Alnaes G.G.; John E.M.; Dork T.; Flyger H.; Dunning A.M.; Wang Q.; Muranen T.A.; Van Hien R.; Figueroa J.; Southey M.C.; Czene K.; Knight J.A.; Tollenaar R.A.E.M.; Beckmann M.W.; Ziogas A.; Christiaens M.-R.; Collee J.M.; Reed M.W.R.; Severi G.; Marme F.; Margolin S.; Olson J.E.; Kosma V.-M.; Kristensen V.N.; Miron A.; Bogdanova N.; Shah M.; Blomqvist C.; Broeks A.; Sherman M.; Phillips K.-A.; Li J.; Liu J.; Glendon G.; Seynaeve C.; Ekici A.B.; Leunen K.; Kriege M.; Cross S.S.; Baglietto L.; Sohn C.; Wang X.; Kataja V.; Borresen-Dale A.-L.; Meyer A.; Easton D.F.; Schmidt M.K.; Bojesen S.E.. - In: JOURNAL OF CLINICAL ONCOLOGY. - ISSN 0732-183X. - STAMPA. - 30:(2012), pp. 4308-4316. [10.1200/JCO.2012.42.7336]