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

Maren Weischer; Børge G. Nordestgaard; Paul Pharoah; Manjeet K. Bolla; Heli Nevanlinna; Laura J. Van't Veer; Montserrat Garcia-Closas; John L. Hopper; Per Hall; Irene L. Andrulis; Peter Devilee; Peter A. Fasching; Hoda Anton-Culver; Diether Lambrechts; Maartje Hooning; Angela Cox; Graham G. Giles; Barbara Burwinkel; Annika Lindblom; Fergus J. Couch; Arto Mannermaa; Grethe Grenaker Alnæs; Esther M. John; Thilo Dörk; Henrik Flyger; Alison M. Dunning; Qin Wang; Taru A. Muranen; Richard Van Hien; Jonine Figueroa; Melissa C. Southey; Kamila Czene; Julia A. Knight; Rob A.E.M. Tollenaar; Matthias W. Beckmann; Argyrios Ziogas; Marie Rose Christiaens; Johanna Margriet Collée; Malcolm W.R. Reed; Gianluca Severi; Frederik Marme; Sara Margolin; Janet E. Olson; Veli Matti Kosma; Vessela N. Kristensen; Alexander Miron; Natalia Bogdanova; Mitul Shah; Carl Blomqvist; Annegien Broeks; Mark Sherman; Kelly Anne Phillips; Jingmei Li; Jianjun Liu; Gord Glendon; Caroline Seynaeve; Arif B. Ekici; Karin Leunen; Mieke Kriege; Simon S. Cross; Laura Baglietto; Christof Sohn; Xianshu Wang; Vesa Kataja; Anne Lise Børresen-Dale; Andreas Meyer; Douglas F. Easton; Marjanka K. Schmidt; Stig E. 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

Maren Weischer, Børge G. Nordestgaard, Paul Pharoah, Manjeet K. Bolla, Heli Nevanlinna, Laura J. Van't Veer, Montserrat Garcia-Closas, John L. Hopper, Per Hall, Irene L. Andrulis, Peter Devilee, Peter A. Fasching, Hoda Anton-Culver, Diether Lambrechts, Maartje Hooning, Angela Cox, Graham G. Giles, Barbara Burwinkel, Annika Lindblom, Fergus J. CouchArto Mannermaa, Grethe Grenaker Alnæs, Esther M. John, Thilo Dörk, Henrik Flyger, Alison M. Dunning, Qin Wang, Taru A. Muranen, Richard Van Hien, Jonine Figueroa, Melissa C. Southey, Kamila Czene, Julia A. Knight, Rob A.E.M. Tollenaar, Matthias W. Beckmann, Argyrios Ziogas, Marie Rose Christiaens, Johanna Margriet Collée, Malcolm W.R. Reed, Gianluca Severi, Frederik Marme, Sara Margolin, Janet E. Olson, Veli Matti Kosma, Vessela N. Kristensen, Alexander Miron, Natalia Bogdanova, Mitul Shah, Carl Blomqvist, Annegien Broeks, Mark Sherman, Kelly Anne Phillips, Jingmei Li, Jianjun Liu, Gord Glendon, Caroline Seynaeve, Arif B. Ekici, Karin Leunen, Mieke Kriege, Simon S. Cross, Laura Baglietto, Christof Sohn, Xianshu Wang, Vesa Kataja, Anne Lise Børresen-Dale, Andreas Meyer, Douglas F. Easton, Marjanka K. Schmidt, Stig E. Bojesen

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

113 Scopus citations

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-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.

Original language	English (US)
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
State	Published - Dec 10 2012

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1200/JCO.2012.42.7336

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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., ... Bojesen, S. E. (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

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, Maren; Nordestgaard, Børge G.; Pharoah, Paul et al.
In: Journal of Clinical Oncology, Vol. 30, No. 35, 10.12.2012, p. 4308-4316.

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

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, Alnæs, GG, John, EM, Dörk, 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, Collée, JM, 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, 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 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

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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-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.",

author = "Maren Weischer and Nordestgaard, {B{\o}rge G.} and Paul Pharoah and Bolla, {Manjeet K.} and Heli Nevanlinna and {Van't Veer}, {Laura J.} and Montserrat Garcia-Closas and Hopper, {John L.} and Per Hall and Andrulis, {Irene L.} and Peter Devilee and Fasching, {Peter A.} and Hoda Anton-Culver and Diether Lambrechts and Maartje Hooning and Angela Cox and Giles, {Graham G.} and Barbara Burwinkel and Annika Lindblom and Couch, {Fergus J.} and Arto Mannermaa and Aln{\ae}s, {Grethe Grenaker} and John, {Esther M.} and Thilo D{\"o}rk and Henrik Flyger and Dunning, {Alison M.} and Qin Wang and Muranen, {Taru A.} and {Van Hien}, Richard and Jonine Figueroa and Southey, {Melissa C.} and Kamila Czene and Knight, {Julia A.} and Tollenaar, {Rob A.E.M.} and Beckmann, {Matthias W.} and Argyrios Ziogas and Christiaens, {Marie Rose} and Coll{\'e}e, {Johanna Margriet} and Reed, {Malcolm W.R.} and Gianluca Severi and Frederik Marme and Sara Margolin and Olson, {Janet E.} and Kosma, {Veli Matti} and Kristensen, {Vessela N.} and Alexander Miron and Natalia Bogdanova and Mitul Shah and Carl Blomqvist and Annegien Broeks and Mark Sherman and Phillips, {Kelly Anne} and Jingmei Li and Jianjun Liu and Gord Glendon and Caroline Seynaeve and Ekici, {Arif B.} and Karin Leunen and Mieke Kriege and Cross, {Simon S.} and Laura Baglietto and Christof Sohn and Xianshu Wang and Vesa Kataja and B{\o}rresen-Dale, {Anne Lise} and Andreas Meyer and Easton, {Douglas F.} and Schmidt, {Marjanka K.} and Bojesen, {Stig E.}",

year = "2012",

month = dec,

day = "10",

doi = "10.1200/JCO.2012.42.7336",

language = "English (US)",

volume = "30",

pages = "4308--4316",

journal = "Journal of Clinical Oncology",

issn = "0732-183X",

publisher = "American Society of Clinical Oncology",

number = "35",

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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, Maren

AU - Nordestgaard, Børge G.

AU - Pharoah, Paul

AU - Bolla, Manjeet K.

AU - Nevanlinna, Heli

AU - Van't Veer, Laura J.

AU - Garcia-Closas, Montserrat

AU - Hopper, John L.

AU - Hall, Per

AU - Andrulis, Irene L.

AU - Devilee, Peter

AU - Fasching, Peter A.

AU - Anton-Culver, Hoda

AU - Lambrechts, Diether

AU - Hooning, Maartje

AU - Cox, Angela

AU - Giles, Graham G.

AU - Burwinkel, Barbara

AU - Lindblom, Annika

AU - Couch, Fergus J.

AU - Mannermaa, Arto

AU - Alnæs, Grethe Grenaker

AU - John, Esther M.

AU - Dörk, Thilo

AU - Flyger, Henrik

AU - Dunning, Alison M.

AU - Wang, Qin

AU - Muranen, Taru A.

AU - Van Hien, Richard

AU - Figueroa, Jonine

AU - Southey, Melissa C.

AU - Czene, Kamila

AU - Knight, Julia A.

AU - Tollenaar, Rob A.E.M.

AU - Beckmann, Matthias W.

AU - Ziogas, Argyrios

AU - Christiaens, Marie Rose

AU - Collée, Johanna Margriet

AU - Reed, Malcolm W.R.

AU - Severi, Gianluca

AU - Marme, Frederik

AU - Margolin, Sara

AU - Olson, Janet E.

AU - Kosma, Veli Matti

AU - Kristensen, Vessela N.

AU - Miron, Alexander

AU - Bogdanova, Natalia

AU - Shah, Mitul

AU - Blomqvist, Carl

AU - Broeks, Annegien

AU - Sherman, Mark

AU - Phillips, Kelly Anne

AU - Li, Jingmei

AU - Liu, Jianjun

AU - Glendon, Gord

AU - Seynaeve, Caroline

AU - Ekici, Arif B.

AU - Leunen, Karin

AU - Kriege, Mieke

AU - Cross, Simon S.

AU - Baglietto, Laura

AU - Sohn, Christof

AU - Wang, Xianshu

AU - Kataja, Vesa

AU - Børresen-Dale, Anne Lise

AU - Meyer, Andreas

AU - Easton, Douglas F.

AU - Schmidt, Marjanka K.

AU - Bojesen, Stig E.

PY - 2012/12/10

Y1 - 2012/12/10

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-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.

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-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.

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JO - Journal of Clinical Oncology

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

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