Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk

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Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk. / Kramer, Iris; Hooning, Maartje J; Mavaddat, Nasim; Hauptmann, Michael; Keeman, Renske; Steyerberg, Ewout W; Giardiello, Daniele; Antoniou, Antonis C; Pharoah, Paul D P; Canisius, Sander; Abu-Ful, Zumuruda; Andrulis, Irene L; Anton-Culver, Hoda; Aronson, Kristan J; Augustinsson, Annelie; Becher, Heiko; Beckmann, Matthias W; Behrens, Sabine; Benitez, Javier; Bermisheva, Marina; Bogdanova, Natalia V; Bojesen, Stig E; Bolla, Manjeet K; Bonanni, Bernardo; Brauch, Hiltrud; Bremer, Michael; Brucker, Sara Y; Burwinkel, Barbara; Castelao, Jose E; Chan, Tsun L; Chang-Claude, Jenny; Chanock, Stephen J; Chenevix-Trench, Georgia; Choi, Ji-Yeob; Clarke, Christine L; Collée, J Margriet; Couch, Fergus J; Cox, Angela; Cross, Simon S; Czene, Kamila; Daly, Mary B; Devilee, Peter; Dörk, Thilo; Dos-Santos-Silva, Isabel; Dunning, Alison M; Dwek, Miriam; Eccles, Diana M; Evans, D Gareth; Flyger, Henrik; Scott, Christopher; NBCS Collaborators.

In: American Journal of Human Genetics, Vol. 107, No. 5, 2020, p. 837-848.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Kramer, I, Hooning, MJ, Mavaddat, N, Hauptmann, M, Keeman, R, Steyerberg, EW, Giardiello, D, Antoniou, AC, Pharoah, PDP, Canisius, S, Abu-Ful, Z, Andrulis, IL, Anton-Culver, H, Aronson, KJ, Augustinsson, A, Becher, H, Beckmann, MW, Behrens, S, Benitez, J, Bermisheva, M, Bogdanova, NV, Bojesen, SE, Bolla, MK, Bonanni, B, Brauch, H, Bremer, M, Brucker, SY, Burwinkel, B, Castelao, JE, Chan, TL, Chang-Claude, J, Chanock, SJ, Chenevix-Trench, G, Choi, J-Y, Clarke, CL, Collée, JM, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, Devilee, P, Dörk, T, Dos-Santos-Silva, I, Dunning, AM, Dwek, M, Eccles, DM, Evans, DG, Flyger, H, Scott, C & NBCS Collaborators 2020, 'Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk', American Journal of Human Genetics, vol. 107, no. 5, pp. 837-848. https://doi.org/10.1016/j.ajhg.2020.09.001

APA

Kramer, I., Hooning, M. J., Mavaddat, N., Hauptmann, M., Keeman, R., Steyerberg, E. W., Giardiello, D., Antoniou, A. C., Pharoah, P. D. P., Canisius, S., Abu-Ful, Z., Andrulis, I. L., Anton-Culver, H., Aronson, K. J., Augustinsson, A., Becher, H., Beckmann, M. W., Behrens, S., Benitez, J., ... NBCS Collaborators (2020). Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk. American Journal of Human Genetics, 107(5), 837-848. https://doi.org/10.1016/j.ajhg.2020.09.001

Vancouver

Kramer I, Hooning MJ, Mavaddat N, Hauptmann M, Keeman R, Steyerberg EW et al. Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk. American Journal of Human Genetics. 2020;107(5):837-848. https://doi.org/10.1016/j.ajhg.2020.09.001

Author

Kramer, Iris ; Hooning, Maartje J ; Mavaddat, Nasim ; Hauptmann, Michael ; Keeman, Renske ; Steyerberg, Ewout W ; Giardiello, Daniele ; Antoniou, Antonis C ; Pharoah, Paul D P ; Canisius, Sander ; Abu-Ful, Zumuruda ; Andrulis, Irene L ; Anton-Culver, Hoda ; Aronson, Kristan J ; Augustinsson, Annelie ; Becher, Heiko ; Beckmann, Matthias W ; Behrens, Sabine ; Benitez, Javier ; Bermisheva, Marina ; Bogdanova, Natalia V ; Bojesen, Stig E ; Bolla, Manjeet K ; Bonanni, Bernardo ; Brauch, Hiltrud ; Bremer, Michael ; Brucker, Sara Y ; Burwinkel, Barbara ; Castelao, Jose E ; Chan, Tsun L ; Chang-Claude, Jenny ; Chanock, Stephen J ; Chenevix-Trench, Georgia ; Choi, Ji-Yeob ; Clarke, Christine L ; Collée, J Margriet ; Couch, Fergus J ; Cox, Angela ; Cross, Simon S ; Czene, Kamila ; Daly, Mary B ; Devilee, Peter ; Dörk, Thilo ; Dos-Santos-Silva, Isabel ; Dunning, Alison M ; Dwek, Miriam ; Eccles, Diana M ; Evans, D Gareth ; Flyger, Henrik ; Scott, Christopher ; NBCS Collaborators. / Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk. In: American Journal of Human Genetics. 2020 ; Vol. 107, No. 5. pp. 837-848.

Bibtex

@article{cf305919a2084c83bf6b7d7490313320,

title = "Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk",

abstract = "Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS313 was quantified using Cox regression analyses. We assessed PRS313 interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS313 was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS313 was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18-1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02-1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10th percentile and 20.5% at the 90th percentile of PRS313. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS313 alone was 0.563 (95%CI = 0.547-0.586). In conclusion, PRS313 is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies.",

keywords = "Adult, Aged, Asian Continental Ancestry Group, Breast Neoplasms/diagnosis, Cohort Studies, Estrogen Receptor alpha/genetics, European Continental Ancestry Group, Female, Gene Expression, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Humans, Middle Aged, Multifactorial Inheritance, Neoadjuvant Therapy/methods, Neoplasms, Second Primary/diagnosis, Prognosis, Proportional Hazards Models, Receptor, ErbB-2/genetics, Receptors, Progesterone/genetics, Risk Assessment",

author = "Iris Kramer and Hooning, {Maartje J} and Nasim Mavaddat and Michael Hauptmann and Renske Keeman and Steyerberg, {Ewout W} and Daniele Giardiello and Antoniou, {Antonis C} and Pharoah, {Paul D P} and Sander Canisius and Zumuruda Abu-Ful and Andrulis, {Irene L} and Hoda Anton-Culver and Aronson, {Kristan J} and Annelie Augustinsson and Heiko Becher and Beckmann, {Matthias W} and Sabine Behrens and Javier Benitez and Marina Bermisheva and Bogdanova, {Natalia V} and Bojesen, {Stig E} and Bolla, {Manjeet K} and Bernardo Bonanni and Hiltrud Brauch and Michael Bremer and Brucker, {Sara Y} and Barbara Burwinkel and Castelao, {Jose E} and Chan, {Tsun L} and Jenny Chang-Claude and Chanock, {Stephen J} and Georgia Chenevix-Trench and Ji-Yeob Choi and Clarke, {Christine L} and Coll{\'e}e, {J Margriet} and Couch, {Fergus J} and Angela Cox and Cross, {Simon S} and Kamila Czene and Daly, {Mary B} and Peter Devilee and Thilo D{\"o}rk and Isabel Dos-Santos-Silva and Dunning, {Alison M} and Miriam Dwek and Eccles, {Diana M} and Evans, {D Gareth} and Henrik Flyger and Christopher Scott and {NBCS Collaborators}",

year = "2020",

doi = "10.1016/j.ajhg.2020.09.001",

language = "English",

volume = "107",

pages = "837--848",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "5",

}

RIS

TY - JOUR

T1 - Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk

AU - Kramer, Iris

AU - Hooning, Maartje J

AU - Mavaddat, Nasim

AU - Hauptmann, Michael

AU - Keeman, Renske

AU - Steyerberg, Ewout W

AU - Giardiello, Daniele

AU - Antoniou, Antonis C

AU - Pharoah, Paul D P

AU - Canisius, Sander

AU - Abu-Ful, Zumuruda

AU - Andrulis, Irene L

AU - Anton-Culver, Hoda

AU - Aronson, Kristan J

AU - Augustinsson, Annelie

AU - Becher, Heiko

AU - Beckmann, Matthias W

AU - Behrens, Sabine

AU - Benitez, Javier

AU - Bermisheva, Marina

AU - Bogdanova, Natalia V

AU - Bojesen, Stig E

AU - Bolla, Manjeet K

AU - Bonanni, Bernardo

AU - Brauch, Hiltrud

AU - Bremer, Michael

AU - Brucker, Sara Y

AU - Burwinkel, Barbara

AU - Castelao, Jose E

AU - Chan, Tsun L

AU - Chang-Claude, Jenny

AU - Chanock, Stephen J

AU - Chenevix-Trench, Georgia

AU - Choi, Ji-Yeob

AU - Clarke, Christine L

AU - Collée, J Margriet

AU - Couch, Fergus J

AU - Cox, Angela

AU - Cross, Simon S

AU - Czene, Kamila

AU - Daly, Mary B

AU - Devilee, Peter

AU - Dörk, Thilo

AU - Dos-Santos-Silva, Isabel

AU - Dunning, Alison M

AU - Dwek, Miriam

AU - Eccles, Diana M

AU - Evans, D Gareth

AU - Flyger, Henrik

AU - Scott, Christopher

AU - NBCS Collaborators

PY - 2020

Y1 - 2020

N2 - Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS313 was quantified using Cox regression analyses. We assessed PRS313 interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS313 was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS313 was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18-1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02-1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10th percentile and 20.5% at the 90th percentile of PRS313. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS313 alone was 0.563 (95%CI = 0.547-0.586). In conclusion, PRS313 is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies.

AB - Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS313 was quantified using Cox regression analyses. We assessed PRS313 interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS313 was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS313 was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18-1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02-1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10th percentile and 20.5% at the 90th percentile of PRS313. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS313 alone was 0.563 (95%CI = 0.547-0.586). In conclusion, PRS313 is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies.

KW - Adult

KW - Aged

KW - Asian Continental Ancestry Group

KW - Breast Neoplasms/diagnosis

KW - Cohort Studies

KW - Estrogen Receptor alpha/genetics

KW - European Continental Ancestry Group

KW - Female

KW - Gene Expression

KW - Genetic Predisposition to Disease

KW - Genome, Human

KW - Genome-Wide Association Study

KW - Humans

KW - Middle Aged

KW - Multifactorial Inheritance

KW - Neoadjuvant Therapy/methods

KW - Neoplasms, Second Primary/diagnosis

KW - Prognosis

KW - Proportional Hazards Models

KW - Receptor, ErbB-2/genetics

KW - Receptors, Progesterone/genetics

KW - Risk Assessment

U2 - 10.1016/j.ajhg.2020.09.001

DO - 10.1016/j.ajhg.2020.09.001

M3 - Journal article

C2 - 33022221

VL - 107

SP - 837

EP - 848

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 5

ER -

ID: 260197278