CHEK2*1100delC Heterozygosity in Women With Breast Cancer Associated With Early Death, Breast Cancer-Specific Death, and Increased Risk of a Second Breast Cancer

M Weischer; BG Nordestgaard; P Pharoah; MK Bolla; H Nevanlinna; LJ (Laura) van 't Veer; M Garcia-Closas; JL Hopper; P Hall; IL Andrulis; P Devilee; PA Fasching; H Anton-Culver; D Lambrechts; M Hooning; A Cox; GG Giles; B Burwinkel; A Lindblom; FJ Couch; A Mannermaa; GG Alnaes; EM John; T Dork; H Flyger; AM Dunning; Q (Qing) Wang; TA Muranen; R van Hien; J Figueroa; MC Southey; K Czene; JA Knight; RAEM Tollenaar; MW Beckmann; A Ziogas; MR Christiaens; Margriet Collee; MWR Reed; G Severi; F Marme; S Margolin; JE Olson; VM Kosma; VN Kristensen; A Miron; N Bogdanova; M Shah; C Blomqvist; A Broeks; M Sherman; KA Phillips; JM Li; JJ Liu; G Glendon; Caroline Seynaeve; AB Ekici; K Leunen; Mieke Kriege; SS Cross; L Baglietto; C Sohn; XS Wang; V Kataja; AL Borresen-Dale; A Meyer; DF Easton; Marjanka K Schmidt; SE Bojesen

doi:10.1200/JCO.2012.42.7336

CHEK2*1100delC Heterozygosity in Women With Breast Cancer Associated With Early Death, Breast Cancer-Specific Death, and Increased Risk of a Second Breast Cancer

M Weischer, BG Nordestgaard, P Pharoah, MK Bolla, H Nevanlinna, LJ (Laura) van 't Veer, M Garcia-Closas, JL Hopper, P Hall, IL Andrulis, P Devilee, PA Fasching, H Anton-Culver, D Lambrechts, M Hooning, A Cox, GG Giles, B Burwinkel, A Lindblom, FJ CouchA Mannermaa, GG Alnaes, EM John, T Dork, H Flyger, AM Dunning, Q (Qing) Wang, TA Muranen, R van Hien, J Figueroa, MC Southey, K Czene, JA Knight, RAEM Tollenaar, MW Beckmann, A Ziogas, MR Christiaens, Margriet Collee, MWR Reed, G Severi, F Marme, S Margolin, JE Olson, VM Kosma, VN Kristensen, A Miron, N Bogdanova, M Shah, C Blomqvist, A Broeks, M Sherman, KA Phillips, JM Li, JJ Liu, G Glendon, Caroline Seynaeve, AB Ekici, K Leunen, Mieke Kriege, SS Cross, L Baglietto, C Sohn, XS Wang, V Kataja, AL Borresen-Dale, A Meyer, DF Easton, Marjanka K Schmidt, SE Bojesen

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

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 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. J Clin Oncol 30: 4308-4316. (C) 2012 by American Society of Clinical Oncology

Original language	Undefined/Unknown
Pages (from-to)	4308-4316
Number of pages	9
Journal	Journal of Clinical Oncology
Volume	30
Issue number	35
DOIs	https://doi.org/10.1200/JCO.2012.42.7336
Publication status	Published - 2012

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EMC MGC-02-96-01
EMC MM-03-86-01

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10.1200/JCO.2012.42.7336

http://hdl.handle.net/1765/64392

Cite this

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., ... Bojesen, SE. (2012). CHEK2*1100delC Heterozygosity in Women With Breast Cancer Associated With Early Death, Breast Cancer-Specific Death, and Increased Risk of a Second Breast Cancer. Journal of Clinical Oncology, 30(35), 4308-4316. https://doi.org/10.1200/JCO.2012.42.7336

@article{fb7402d0f8ef424481e9f5e563b9342a,

title = "CHEK2*1100delC Heterozygosity in Women With Breast Cancer Associated With Early Death, Breast Cancer-Specific Death, and Increased Risk of a Second Breast Cancer",

abstract = "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 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. J Clin Oncol 30: 4308-4316. (C) 2012 by American Society of Clinical Oncology",

author = "M Weischer and BG Nordestgaard and P Pharoah and MK Bolla and H Nevanlinna and {van 't Veer}, {LJ (Laura)} and M Garcia-Closas and JL Hopper and P Hall and IL Andrulis and P Devilee and PA Fasching and H Anton-Culver and D Lambrechts and M Hooning and A Cox and GG Giles and B Burwinkel and A Lindblom and FJ Couch and A Mannermaa and GG Alnaes and EM John and T Dork and H Flyger and AM Dunning and Wang, {Q (Qing)} and TA Muranen and {van Hien}, R and J Figueroa and MC Southey and K Czene and JA Knight and RAEM Tollenaar and MW Beckmann and A Ziogas and MR Christiaens and Margriet Collee and MWR Reed and G Severi and F Marme and S Margolin and JE Olson and VM Kosma and VN Kristensen and A Miron and N Bogdanova and M Shah and C Blomqvist and A Broeks and M Sherman and KA Phillips and JM Li and JJ Liu and G Glendon and Caroline Seynaeve and AB Ekici and K Leunen and Mieke Kriege and SS Cross and L Baglietto and C Sohn and XS Wang and V Kataja and AL Borresen-Dale and A Meyer and DF Easton and Schmidt, {Marjanka K} and SE Bojesen",

year = "2012",

doi = "10.1200/JCO.2012.42.7336",

language = "Undefined/Unknown",

volume = "30",

pages = "4308--4316",

journal = "Journal of Clinical Oncology",

issn = "0732-183X",

publisher = "Lippincott Williams & Wilkins",

number = "35",

}

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, Alnaes, GG, John, EM, Dork, T, Flyger, H, Dunning, AM, Wang, Q, Muranen, TA, van Hien, R, Figueroa, J, Southey, MC, Czene, K, Knight, JA, Tollenaar, RAEM, Beckmann, MW, Ziogas, A, Christiaens, MR, Collee, M, Reed, MWR, 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, JM, Liu, JJ, Glendon, G, Seynaeve, C, Ekici, AB, Leunen, K, Kriege, M, Cross, SS, Baglietto, L, Sohn, C, Wang, XS, Kataja, V, Borresen-Dale, AL, Meyer, A, Easton, DF, Schmidt, MK & Bojesen, SE 2012, 'CHEK2*1100delC Heterozygosity in Women With Breast Cancer Associated With Early Death, Breast Cancer-Specific Death, and Increased Risk of a Second Breast Cancer', Journal of Clinical Oncology, vol. 30, no. 35, pp. 4308-4316. https://doi.org/10.1200/JCO.2012.42.7336

TY - JOUR

T1 - CHEK2*1100delC Heterozygosity in Women With Breast Cancer Associated With Early Death, Breast Cancer-Specific Death, and Increased Risk of a Second Breast Cancer

AU - Weischer, M

AU - Nordestgaard, BG

AU - Pharoah, P

AU - Bolla, MK

AU - Nevanlinna, H

AU - van 't Veer, LJ (Laura)

AU - Garcia-Closas, M

AU - Hopper, JL

AU - Hall, P

AU - Andrulis, IL

AU - Devilee, P

AU - Fasching, PA

AU - Anton-Culver, H

AU - Lambrechts, D

AU - Hooning, M

AU - Cox, A

AU - Giles, GG

AU - Burwinkel, B

AU - Lindblom, A

AU - Couch, FJ

AU - Mannermaa, A

AU - Alnaes, GG

AU - John, EM

AU - Dork, T

AU - Flyger, H

AU - Dunning, AM

AU - Wang, Q (Qing)

AU - Muranen, TA

AU - van Hien, R

AU - Figueroa, J

AU - Southey, MC

AU - Czene, K

AU - Knight, JA

AU - Tollenaar, RAEM

AU - Beckmann, MW

AU - Ziogas, A

AU - Christiaens, MR

AU - Collee, Margriet

AU - Reed, MWR

AU - Severi, G

AU - Marme, F

AU - Margolin, S

AU - Olson, JE

AU - Kosma, VM

AU - Kristensen, VN

AU - Miron, A

AU - Bogdanova, N

AU - Shah, M

AU - Blomqvist, C

AU - Broeks, A

AU - Sherman, M

AU - Phillips, KA

AU - Li, JM

AU - Liu, JJ

AU - Glendon, G

AU - Seynaeve, Caroline

AU - Ekici, AB

AU - Leunen, K

AU - Kriege, Mieke

AU - Cross, SS

AU - Baglietto, L

AU - Sohn, C

AU - Wang, XS

AU - Kataja, V

AU - Borresen-Dale, AL

AU - Meyer, A

AU - Easton, DF

AU - Schmidt, Marjanka K

AU - Bojesen, SE

PY - 2012

Y1 - 2012

N2 - 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 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. J Clin Oncol 30: 4308-4316. (C) 2012 by American Society of Clinical Oncology

AB - 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 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. J Clin Oncol 30: 4308-4316. (C) 2012 by American Society of Clinical Oncology

U2 - 10.1200/JCO.2012.42.7336

DO - 10.1200/JCO.2012.42.7336

M3 - Article

C2 - 23109706

SN - 0732-183X

VL - 30

SP - 4308

EP - 4316

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

IS - 35

ER -