Breast cancer polygenic risk score and contralateral breast cancer risk

Iris Kramer; Maartje J. Hooning; Nasim Mavaddat; Michael Hauptmann; Renske Keeman; Ewout W. Steyerberg; Daniele Giardiello; Antonis C. Antoniou; Paul D. P. Pharoah; Sander Canisius; Zumuruda Abu-Ful; Irene L. Andrulis; Hoda Anton-Culver; Kristan J. Aronson; Annelie Augustinsson; Heiko Becher; Matthias W. Beckmann; Sabine Behrens; Javier Benitez; Marina Bermisheva; Natalia V. Bogdanova; Stig E. Bojesen; Manjeet K. Bolla; Bernardo Bonanni; Hiltrud Brauch; Michael Bremer; Sara Y. Brucker; Barbara Burwinkel; Jose E. Castelao; Tsun L. Chan; Jenny Chang-Claude; Stephen J. Chanock; Georgia Chenevix-Trench; Ji Yeob Choi; Christine Clarke; NBCS Collaborators; J. Margriet Collée; Fergus J. Couch; Angela Cox; Simon S. Cross; Kamila Czene; Mary B. Daly; Peter Devilee; Thilo Dörk; Isabel dos-Santos-Silva; Alison M. Dunning; Miriam Dwek; Diana M. Eccles; D. Gareth Evans; Peter A. Fasching; Henrik Flyger; Manuela Gago-Dominguez; Montserrat García-Closas; José A. García-Sáenz; Graham G. Giles; David E. Goldgar; Anna González-Neira; Christopher A. Haiman; Niclas Håkansson; Ute Hamann; Mikael Hartman; Bernadette A. M. Heemskerk-Gerritsen; Antoinette Hollestelle; John L. Hopper; Ming Feng Hou; Anthony Howell; ABCTB Investigators; kConFab Investigators; Hidemi Ito; Milena Jakimovska; Anna Jakubowska; Wolfgang Janni; Esther M. John; Audrey Jung; Daehee Kang; C. Marleen Kets; Elza Khusnutdinova; Yon Dschun Ko; Vessela N. Kristensen; Allison W. Kurian; Ava Kwong; Diether Lambrechts; Loic Le Marchand; Jingmei Li; Annika Lindblom; Jan Lubiński; Arto Mannermaa; Mehdi Manoochehri; Sara Margolin; Keitaro Matsuo; Dimitrios Mavroudis; Alfons Meindl; Roger L. Milne; Anna Marie Mulligan; Taru A. Muranen; Susan L. Neuhausen; Heli Nevanlinna; William G. Newman; Andrew F. Olshan; Janet E. Olson; Håkan Olsson; Tjoung-Won Park-Simon; Julian Peto; Christos Petridis; Dijana Plaseska-Karanfilska; Nadege Presneau; Katri Pylkäs; Paolo Radice; Gad Rennert; Atocha Romero; Rebecca Roylance; Emmanouil Saloustros; Elinor J. Sawyer; Rita K. Schmutzler; Lukas Schwentner; Christopher Scott; Mee Hoong See; Mitul Shah; Chen Yang Shen; Xiao Ou Shu; Sabine Siesling; Susan Slager; Christof Sohn; Melissa C. Southey; John J. Spinelli; Jennifer Stone; William J. Tapper; Maria Tengström; Soo Hwang Teo; Mary Beth Terry; Rob A. E. M. Tollenaar; Ian Tomlinson; Melissa A. Troester; Celine M. Vachon; Chantal van Ongeval; Elke M. van Veen; Robert Winqvist; Alicja Wolk; Wei Zheng; Argyrios Ziogas; Douglas F. Easton; Per Hall; Marjanka K. Schmidt

doi:10.1016/j.ajhg.2020.09.001

Breast cancer polygenic risk score and contralateral breast cancer risk

Iris Kramer, Maartje J. Hooning, Nasim Mavaddat, Michael Hauptmann, Renske Keeman, Ewout W. Steyerberg, Daniele Giardiello, Antonis C. Antoniou, Paul D. P. Pharoah, Sander Canisius, Zumuruda Abu-Ful, Irene L. Andrulis, Hoda Anton-Culver, Kristan J. Aronson, Annelie Augustinsson, Heiko Becher, Matthias W. Beckmann, Sabine Behrens, Javier Benitez, Marina BermishevaNatalia V. Bogdanova, Stig E. Bojesen, Manjeet K. Bolla, Bernardo Bonanni, Hiltrud Brauch, Michael Bremer, Sara Y. Brucker, Barbara Burwinkel, Jose E. Castelao, Tsun L. Chan, Jenny Chang-Claude, Stephen J. Chanock, Georgia Chenevix-Trench, Ji Yeob Choi, Christine Clarke, NBCS Collaborators, J. Margriet Collée, Fergus J. Couch, Angela Cox, Simon S. Cross, Kamila Czene, Mary B. Daly, Peter Devilee, Thilo Dörk, Isabel dos-Santos-Silva, Alison M. Dunning, Miriam Dwek, Diana M. Eccles, D. Gareth Evans, Peter A. Fasching, Henrik Flyger, Manuela Gago-Dominguez, Montserrat García-Closas, José A. García-Sáenz, Graham G. Giles, David E. Goldgar, Anna González-Neira, Christopher A. Haiman, Niclas Håkansson, Ute Hamann, Mikael Hartman, Bernadette A. M. Heemskerk-Gerritsen, Antoinette Hollestelle, John L. Hopper, Ming Feng Hou, Anthony Howell, ABCTB Investigators, kConFab Investigators, Hidemi Ito, Milena Jakimovska, Anna Jakubowska, Wolfgang Janni, Esther M. John, Audrey Jung, Daehee Kang, C. Marleen Kets, Elza Khusnutdinova, Yon Dschun Ko, Vessela N. Kristensen, Allison W. Kurian, Ava Kwong, Diether Lambrechts, Loic Le Marchand, Jingmei Li, Annika Lindblom, Jan Lubiński, Arto Mannermaa, Mehdi Manoochehri, Sara Margolin, Keitaro Matsuo, Dimitrios Mavroudis, Alfons Meindl, Roger L. Milne, Anna Marie Mulligan, Taru A. Muranen, Susan L. Neuhausen, Heli Nevanlinna, William G. Newman, Andrew F. Olshan, Janet E. Olson, Håkan Olsson, Tjoung-Won Park-Simon, Julian Peto, Christos Petridis, Dijana Plaseska-Karanfilska, Nadege Presneau, Katri Pylkäs, Paolo Radice, Gad Rennert, Atocha Romero, Rebecca Roylance, Emmanouil Saloustros, Elinor J. Sawyer, Rita K. Schmutzler, Lukas Schwentner, Christopher Scott, Mee Hoong See, Mitul Shah, Chen Yang Shen, Xiao Ou Shu, Sabine Siesling, Susan Slager, Christof Sohn, Melissa C. Southey, John J. Spinelli, Jennifer Stone, William J. Tapper, Maria Tengström, Soo Hwang Teo, Mary Beth Terry, Rob A. E. M. Tollenaar, Ian Tomlinson, Melissa A. Troester, Celine M. Vachon, Chantal van Ongeval, Elke M. van Veen, Robert Winqvist, Alicja Wolk, Wei Zheng, Argyrios Ziogas, Douglas F. Easton, Per Hall, Marjanka K. Schmidt^*

^*Corresponding author for this work

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

48 Citations (Scopus)

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 10^th percentile and 20.5% at the 90^th 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.

Original language	English
Pages (from-to)	837-848
Number of pages	12
Journal	American Journal of Human Genetics
Volume	107
Issue number	5
DOIs	https://doi.org/10.1016/j.ajhg.2020.09.001
Publication status	Published - 5 Nov 2020

Keywords

contralateral breast cancer
epidemiology
genetic
polygenic risk score

Access to Document

10.1016/j.ajhg.2020.09.001

Cite this

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., ... Schmidt, M. K. (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

@article{92cf9297b6214ec3a4c99822d990dd25,

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 = "contralateral breast cancer, epidemiology, genetic, polygenic risk score",

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 Choi, {Ji Yeob} and Christine Clarke and {NBCS Collaborators} and B{\o}rresen-Dale, {Anne Lise} and Kristine Sahlberg and Lars Ottestad and Rolf K{\aa}resen and Ellen Schlichting and Holmen, {Marit Muri} and Toril Sauer and Vilde Haakensen and Olav Engebr{\aa}ten and Bj{\o}rn Naume and Alexander Foss{\aa} and Cecile Kiserud and Kristin Reinertsen and {\AA}slaug Helland and Margit Riis and J{\"u}rgen Geisler and Aln{\ae}s, {Grethe Grenaker} 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 Fasching, {Peter A.} and Henrik Flyger and Manuela Gago-Dominguez and Montserrat Garc{\'i}a-Closas and Garc{\'i}a-S{\'a}enz, {Jos{\'e} A.} and Giles, {Graham G.} and Goldgar, {David E.} and Anna Gonz{\'a}lez-Neira and Haiman, {Christopher A.} and Niclas H{\aa}kansson and Ute Hamann and Mikael Hartman and Heemskerk-Gerritsen, {Bernadette A. M.} and Antoinette Hollestelle and Hopper, {John L.} and Hou, {Ming Feng} and Anthony Howell and {ABCTB Investigators} and Deborah Marsh and Rodney Scott and Robert Baxter and Desmond Yip and Jane Carpenter and Alison Davis and Nirmala Pathmanathan and Peter Simpson and Graham, {J. Dinny} and Mythily Sachchithananthan and {kConFab Investigators} and David Amor and Lesley Andrews and Yoland Antill and Rosemary Balleine and Jonathan Beesley and Ian Bennett and Michael Bogwitz and Leon Botes and Meagan Brennan and Melissa Brown and Michael Buckley and Jo Burke and Phyllis Butow and Liz Caldon and Ian Campbell and Deepa Chauhan and Manisha Chauhan and Alice Christian and Paul Cohen and Alison Colley and Ashley Crook and James Cui and Margaret Cummings and Dawson, {Sarah Jane} and Anna deFazio and Martin Delatycki and Rebecca Dickson and Joanne Dixon and Ted Edkins and Stacey Edwards and Gelareh Farshid and Andrew Fellows and Georgina Fenton and Michael Field and James Flanagan and Peter Fong and Laura Forrest and Stephen Fox and Juliet French and Michael Friedlander and Clara Gaff and Mike Gattas and Peter George and Sian Greening and Marion Harris and Stewart Hart and Nick Hayward and John Hopper and Cass Hoskins and Clare Hunt and Paul James and Mark Jenkins and Alexa Kidd and Judy Kirk and Jessica Koehler and James Kollias and Sunil Lakhani and Mitchell Lawrence and Geoff Lindeman and Lara Lipton and Liz Lobb and Graham Mann and McLachlan, {Sue Anne} and Bettina Meiser and Sophie Nightingale and Shona O'Connell and Sarah O'Sullivan and Ortega, {David Gallego} and Nick Pachter and Briony Patterson and Amy Pearn and Kelly Phillips and Ellen Pieper and Edwina Rickard and Bridget Robinson and Mona Saleh and Elizabeth Salisbury and Christobel Saunders and Jodi Saunus and Clare Scott and Adrienne Sexton and Andrew Shelling and Amanda Spurdle and Jessica Taylor and Renea Taylor and Heather Thorne and Alison Trainer and Kathy Tucker and Jane Visvader and Logan Walker and Rachael Williams and Ingrid Winship and Young, {Mary Ann} and Hidemi Ito and Milena Jakimovska and Anna Jakubowska and Wolfgang Janni and John, {Esther M.} and Audrey Jung and Daehee Kang and Kets, {C. Marleen} and Elza Khusnutdinova and Ko, {Yon Dschun} and Kristensen, {Vessela N.} and Kurian, {Allison W.} and Ava Kwong and Diether Lambrechts and {Le Marchand}, Loic and Jingmei Li and Annika Lindblom and Jan Lubi{\'n}ski and Arto Mannermaa and Mehdi Manoochehri and Sara Margolin and Keitaro Matsuo and Dimitrios Mavroudis and Alfons Meindl and Milne, {Roger L.} and Mulligan, {Anna Marie} and Muranen, {Taru A.} and Neuhausen, {Susan L.} and Heli Nevanlinna and Newman, {William G.} and Olshan, {Andrew F.} and Olson, {Janet E.} and H{\aa}kan Olsson and Tjoung-Won Park-Simon and Julian Peto and Christos Petridis and Dijana Plaseska-Karanfilska and Nadege Presneau and Katri Pylk{\"a}s and Paolo Radice and Gad Rennert and Atocha Romero and Rebecca Roylance and Emmanouil Saloustros and Sawyer, {Elinor J.} and Schmutzler, {Rita K.} and Lukas Schwentner and Christopher Scott and See, {Mee Hoong} and Mitul Shah and Shen, {Chen Yang} and Shu, {Xiao Ou} and Sabine Siesling and Susan Slager and Christof Sohn and Southey, {Melissa C.} and Spinelli, {John J.} and Jennifer Stone and Tapper, {William J.} and Maria Tengstr{\"o}m and Teo, {Soo Hwang} and Terry, {Mary Beth} and Tollenaar, {Rob A. E. M.} and Ian Tomlinson and Troester, {Melissa A.} and Vachon, {Celine M.} and {van Ongeval}, Chantal and {van Veen}, {Elke M.} and Robert Winqvist and Alicja Wolk and Wei Zheng and Argyrios Ziogas and Easton, {Douglas F.} and Per Hall and Schmidt, {Marjanka K.}",

year = "2020",

month = nov,

day = "5",

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",

}

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, JY, Clarke, C, NBCS Collaborators, 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, Fasching, PA, Flyger, H, Gago-Dominguez, M, García-Closas, M, García-Sáenz, JA, Giles, GG, Goldgar, DE, González-Neira, A, Haiman, CA, Håkansson, N, Hamann, U, Hartman, M, Heemskerk-Gerritsen, BAM, Hollestelle, A, Hopper, JL, Hou, MF, Howell, A, ABCTB Investigators, kConFab Investigators, Ito, H, Jakimovska, M, Jakubowska, A, Janni, W, John, EM, Jung, A, Kang, D, Kets, CM, Khusnutdinova, E, Ko, YD, Kristensen, VN, Kurian, AW, Kwong, A, Lambrechts, D, Le Marchand, L, Li, J, Lindblom, A, Lubiński, J, Mannermaa, A, Manoochehri, M, Margolin, S, Matsuo, K, Mavroudis, D, Meindl, A, Milne, RL, Mulligan, AM, Muranen, TA, Neuhausen, SL, Nevanlinna, H, Newman, WG, Olshan, AF, Olson, JE, Olsson, H, Park-Simon, T-W, Peto, J, Petridis, C, Plaseska-Karanfilska, D, Presneau, N, Pylkäs, K, Radice, P, Rennert, G, Romero, A, Roylance, R, Saloustros, E, Sawyer, EJ, Schmutzler, RK, Schwentner, L, Scott, C, See, MH, Shah, M, Shen, CY, Shu, XO, Siesling, S, Slager, S, Sohn, C, Southey, MC, Spinelli, JJ, Stone, J, Tapper, WJ, Tengström, M, Teo, SH, Terry, MB, Tollenaar, RAEM, Tomlinson, I, Troester, MA, Vachon, CM, van Ongeval, C, van Veen, EM, Winqvist, R, Wolk, A, Zheng, W, Ziogas, A, Easton, DF, Hall, P & Schmidt, MK 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

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

AU - NBCS Collaborators

AU - Børresen-Dale, Anne Lise

AU - Sahlberg, Kristine

AU - Ottestad, Lars

AU - Kåresen, Rolf

AU - Schlichting, Ellen

AU - Holmen, Marit Muri

AU - Sauer, Toril

AU - Haakensen, Vilde

AU - Engebråten, Olav

AU - Naume, Bjørn

AU - Fosså, Alexander

AU - Kiserud, Cecile

AU - Reinertsen, Kristin

AU - Helland, Åslaug

AU - Riis, Margit

AU - Geisler, Jürgen

AU - Alnæs, Grethe Grenaker

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 - Fasching, Peter A.

AU - Flyger, Henrik

AU - Gago-Dominguez, Manuela

AU - García-Closas, Montserrat

AU - García-Sáenz, José A.

AU - Giles, Graham G.

AU - Goldgar, David E.

AU - González-Neira, Anna

AU - Haiman, Christopher A.

AU - Håkansson, Niclas

AU - Hamann, Ute

AU - Hartman, Mikael

AU - Heemskerk-Gerritsen, Bernadette A. M.

AU - Hollestelle, Antoinette

AU - Hopper, John L.

AU - Hou, Ming Feng

AU - Howell, Anthony

AU - ABCTB Investigators

AU - Marsh, Deborah

AU - Scott, Rodney

AU - Baxter, Robert

AU - Yip, Desmond

AU - Carpenter, Jane

AU - Davis, Alison

AU - Pathmanathan, Nirmala

AU - Simpson, Peter

AU - Graham, J. Dinny

AU - Sachchithananthan, Mythily

AU - kConFab Investigators

AU - Amor, David

AU - Andrews, Lesley

AU - Antill, Yoland

AU - Balleine, Rosemary

AU - Beesley, Jonathan

AU - Bennett, Ian

AU - Bogwitz, Michael

AU - Botes, Leon

AU - Brennan, Meagan

AU - Brown, Melissa

AU - Buckley, Michael

AU - Burke, Jo

AU - Butow, Phyllis

AU - Caldon, Liz

AU - Campbell, Ian

AU - Chauhan, Deepa

AU - Chauhan, Manisha

AU - Christian, Alice

AU - Cohen, Paul

AU - Colley, Alison

AU - Crook, Ashley

AU - Cui, James

AU - Cummings, Margaret

AU - Dawson, Sarah Jane

AU - deFazio, Anna

AU - Delatycki, Martin

AU - Dickson, Rebecca

AU - Dixon, Joanne

AU - Edkins, Ted

AU - Edwards, Stacey

AU - Farshid, Gelareh

AU - Fellows, Andrew

AU - Fenton, Georgina

AU - Field, Michael

AU - Flanagan, James

AU - Fong, Peter

AU - Forrest, Laura

AU - Fox, Stephen

AU - French, Juliet

AU - Friedlander, Michael

AU - Gaff, Clara

AU - Gattas, Mike

AU - George, Peter

AU - Greening, Sian

AU - Harris, Marion

AU - Hart, Stewart

AU - Hayward, Nick

AU - Hopper, John

AU - Hoskins, Cass

AU - Hunt, Clare

AU - James, Paul

AU - Jenkins, Mark

AU - Kidd, Alexa

AU - Kirk, Judy

AU - Koehler, Jessica

AU - Kollias, James

AU - Lakhani, Sunil

AU - Lawrence, Mitchell

AU - Lindeman, Geoff

AU - Lipton, Lara

AU - Lobb, Liz

AU - Mann, Graham

AU - McLachlan, Sue Anne

AU - Meiser, Bettina

AU - Nightingale, Sophie

AU - O'Connell, Shona

AU - O'Sullivan, Sarah

AU - Ortega, David Gallego

AU - Pachter, Nick

AU - Patterson, Briony

AU - Pearn, Amy

AU - Phillips, Kelly

AU - Pieper, Ellen

AU - Rickard, Edwina

AU - Robinson, Bridget

AU - Saleh, Mona

AU - Salisbury, Elizabeth

AU - Saunders, Christobel

AU - Saunus, Jodi

AU - Scott, Clare

AU - Sexton, Adrienne

AU - Shelling, Andrew

AU - Spurdle, Amanda

AU - Taylor, Jessica

AU - Taylor, Renea

AU - Thorne, Heather

AU - Trainer, Alison

AU - Tucker, Kathy

AU - Visvader, Jane

AU - Walker, Logan

AU - Williams, Rachael

AU - Winship, Ingrid

AU - Young, Mary Ann

AU - Ito, Hidemi

AU - Jakimovska, Milena

AU - Jakubowska, Anna

AU - Janni, Wolfgang

AU - John, Esther M.

AU - Jung, Audrey

AU - Kang, Daehee

AU - Kets, C. Marleen

AU - Khusnutdinova, Elza

AU - Ko, Yon Dschun

AU - Kristensen, Vessela N.

AU - Kurian, Allison W.

AU - Kwong, Ava

AU - Lambrechts, Diether

AU - Le Marchand, Loic

AU - Li, Jingmei

AU - Lindblom, Annika

AU - Lubiński, Jan

AU - Mannermaa, Arto

AU - Manoochehri, Mehdi

AU - Margolin, Sara

AU - Matsuo, Keitaro

AU - Mavroudis, Dimitrios

AU - Meindl, Alfons

AU - Milne, Roger L.

AU - Mulligan, Anna Marie

AU - Muranen, Taru A.

AU - Neuhausen, Susan L.

AU - Nevanlinna, Heli

AU - Newman, William G.

AU - Olshan, Andrew F.

AU - Olson, Janet E.

AU - Olsson, Håkan

AU - Park-Simon, Tjoung-Won

AU - Peto, Julian

AU - Petridis, Christos

AU - Plaseska-Karanfilska, Dijana

AU - Presneau, Nadege

AU - Pylkäs, Katri

AU - Radice, Paolo

AU - Rennert, Gad

AU - Romero, Atocha

AU - Roylance, Rebecca

AU - Saloustros, Emmanouil

AU - Sawyer, Elinor J.

AU - Schmutzler, Rita K.

AU - Schwentner, Lukas

AU - Scott, Christopher

AU - See, Mee Hoong

AU - Shah, Mitul

AU - Shen, Chen Yang

AU - Shu, Xiao Ou

AU - Siesling, Sabine

AU - Slager, Susan

AU - Sohn, Christof

AU - Southey, Melissa C.

AU - Spinelli, John J.

AU - Stone, Jennifer

AU - Tapper, William J.

AU - Tengström, Maria

AU - Teo, Soo Hwang

AU - Terry, Mary Beth

AU - Tollenaar, Rob A. E. M.

AU - Tomlinson, Ian

AU - Troester, Melissa A.

AU - Vachon, Celine M.

AU - van Ongeval, Chantal

AU - van Veen, Elke M.

AU - Winqvist, Robert

AU - Wolk, Alicja

AU - Zheng, Wei

AU - Ziogas, Argyrios

AU - Easton, Douglas F.

AU - Hall, Per

AU - Schmidt, Marjanka K.

PY - 2020/11/5

Y1 - 2020/11/5

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 - contralateral breast cancer

KW - epidemiology

KW - genetic

KW - polygenic risk score

UR - http://www.scopus.com/inward/record.url?scp=85094963024&partnerID=8YFLogxK

U2 - 10.1016/j.ajhg.2020.09.001

DO - 10.1016/j.ajhg.2020.09.001

M3 - Article

C2 - 33022221

AN - SCOPUS:85094963024

SN - 0002-9297

VL - 107

SP - 837

EP - 848

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 5

ER -

Breast cancer polygenic risk score and contralateral breast cancer risk

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this