Associations of a Breast Cancer Polygenic Risk Score With Tumor Characteristics and Survival

Josephine M.N. Lopes Cardozo; Irene L. Andrulis; Stig E. Bojesen; Thilo Dörk; Diana M. Eccles; Peter A. Fasching; Maartje J. Hooning; Renske Keeman; Heli Nevanlinna; Emiel J.T. Rutgers; Douglas F. Easton; Per Hall; Paul D.P. Pharoah; Laura J. Van 't Veer; Marjanka K. Schmidt; Thomas U. Ahearn; Hoda Anton-Culver; Volker Arndt; Paul L. Auer; Annelie Augustinsson; Laura E. Beane Freeman; Heiko Becher; Matthias W. Beckmann; Sabine Behrens; Javier Benitez; Marina Bermisheva; Carl Blomqvist; Manjeet K. Bolla; Bernardo Bonanni; Terry Boyle; Hermann Brenner; Sara Y. Brucker; Thomas Brüning; Barbara Burwinkel; Saundra S. Buys; Nicola J. Camp; Federico Canzian; Fatima Cardoso; Jose E. Castelao; Melissa H. Cessna; Tsun L. Chan; Jenny Chang-Claude; Georgia Chenevix-Trench; Ji Yeob Choi; Sarah V. Colonna; Ellen Copson; Fergus J. Couch; Angela Cox; Simon S. Cross; Kamila Czene; Mary B. Daly; Joe Dennis; Peter Devilee; Caroline A. Drukker; Alison M. Dunning; Miriam Dwek; A. Heather Eliassen; Christoph Engel; D. Gareth Evans; Jonine D. Figueroa; Olivia Fletcher; Henrik Flyger; Manuela Gago-Dominguez; Montserrat García-Closas; José A. García-Sáenz; Jeanine Genkinger; Graham G. Giles; Anna González-Neira; Pascal Guénel; Melanie Gündert; Eric Hahnen; Christopher A. Haiman; Niclas Håkansson; Ute Hamann; Mikael Hartman; Bernadette A.M. Heemskerk-Gerritsen; Alexander Hein; Weang Kee Ho; Reiner Hoppe; John L. Hopper; Richard S. Houlston; Anthony Howell; David J. Hunter; Hidemi Ito; Anna Jakubowska; Helena Jernström; Esther M. John; Nichola Johnson; Michael E. Jones; Vijai Joseph; Rudolf Kaaks; Daehee Kang; Sung Won Kim; Cari M. Kitahara; Linetta B. Koppert; Veli Matti Kosma; Peter Kraft; Vessela N. Kristensen; Katerina Kubelka-Sabit; Stella Koutros; Allison W. Kurian; Ava Kwong; James V. Lacey; Diether Lambrechts; Loic Le Marchand; Jingmei Li; Jan Lubiński; Michael Lush; Arto Mannermaa; Mehdi Manoochehri; Sara Margolin; Keitaro Matsuo; Dimitrios Mavroudis; Kyriaki Michailidou; Roger L. Milne; Nur Aishah Mohd Taib; Anna Marie Mulligan; Patrick Neven; William G. Newman; Nadia Obi; Kenneth Offit; Andrew F. Olshan; Sue K. Park; Tjoung Won Park-Simon; Alpa V. Patel; Dijana Plaseska-Karanfilska; Coralie Poncet; Ross L. Prentice; Nadege Presneau; Renate Prevos; Katri Pylkäs; Paolo Radice; Gad Rennert; Hedy S. Rennert; Atocha Romero; Emmanouil Saloustros; Elinor J. Sawyer; Rita K. Schmutzler; Lukas Schwentner; Christopher Scott; Mitul Shah; Chen Yang Shen; Xiao Ou Shu; Xueling Sim; Melissa C. Southey; Jennifer Stone; Daniel O. Stram; Rulla M. Tamimi; Soo Hwang Teo; Lauren R. Teras; Mary Beth Terry; Katarzyna Tomczyk; Ian Tomlinson; Melissa A. Troester; Thérèse Truong; Celine M. Vachon; Chantal Van Ongeval; Qin Wang; Barbara Wappenschmidt; Camilla Wendt; Robert Winqvist; Alicja Wolk; Anna H. Wu; Siddhartha Yadav; Cheng Har Yip; Wei Zheng; Argyrios Ziogas

doi:10.1200/JCO.22.01978

Associations of a Breast Cancer Polygenic Risk Score With Tumor Characteristics and Survival

Josephine M.N. Lopes Cardozo, Irene L. Andrulis, Stig E. Bojesen, Thilo Dörk, Diana M. Eccles, Peter A. Fasching, Maartje J. Hooning, Renske Keeman, Heli Nevanlinna, Emiel J.T. Rutgers, Douglas F. Easton, Per Hall, Paul D.P. Pharoah, Laura J. Van 't Veer, Marjanka K. Schmidt, Thomas U. Ahearn, Hoda Anton-Culver, Volker Arndt, Paul L. Auer, Annelie AugustinssonLaura E. Beane Freeman, Heiko Becher, Matthias W. Beckmann, Sabine Behrens, Javier Benitez, Marina Bermisheva, Carl Blomqvist, Manjeet K. Bolla, Bernardo Bonanni, Terry Boyle, Hermann Brenner, Sara Y. Brucker, Thomas Brüning, Barbara Burwinkel, Saundra S. Buys, Nicola J. Camp, Federico Canzian, Fatima Cardoso, Jose E. Castelao, Melissa H. Cessna, Tsun L. Chan, Jenny Chang-Claude, Georgia Chenevix-Trench, Ji Yeob Choi, Sarah V. Colonna, Ellen Copson, Fergus J. Couch, Angela Cox, Simon S. Cross, Kamila Czene, Mary B. Daly, Joe Dennis, Peter Devilee, Caroline A. Drukker, Alison M. Dunning, Miriam Dwek, A. Heather Eliassen, Christoph Engel, D. Gareth Evans, Jonine D. Figueroa, Olivia Fletcher, Henrik Flyger, Manuela Gago-Dominguez, Montserrat García-Closas, José A. García-Sáenz, Jeanine Genkinger, Graham G. Giles, Anna González-Neira, Pascal Guénel, Melanie Gündert, Eric Hahnen, Christopher A. Haiman, Niclas Håkansson, Ute Hamann, Mikael Hartman, Bernadette A.M. Heemskerk-Gerritsen, Alexander Hein, Weang Kee Ho, Reiner Hoppe, John L. Hopper, Richard S. Houlston, Anthony Howell, David J. Hunter, Hidemi Ito, Anna Jakubowska, Helena Jernström, Esther M. John, Nichola Johnson, Michael E. Jones, Vijai Joseph, Rudolf Kaaks, Daehee Kang, Sung Won Kim, Cari M. Kitahara, Linetta B. Koppert, Veli Matti Kosma, Peter Kraft, Vessela N. Kristensen, Katerina Kubelka-Sabit, Stella Koutros, Allison W. Kurian, Ava Kwong, James V. Lacey, Diether Lambrechts, Loic Le Marchand, Jingmei Li, Jan Lubiński, Michael Lush, Arto Mannermaa, Mehdi Manoochehri, Sara Margolin, Keitaro Matsuo, Dimitrios Mavroudis, Kyriaki Michailidou, Roger L. Milne, Nur Aishah Mohd Taib, Anna Marie Mulligan, Patrick Neven, William G. Newman, Nadia Obi, Kenneth Offit, Andrew F. Olshan, Sue K. Park, Tjoung Won Park-Simon, Alpa V. Patel, Dijana Plaseska-Karanfilska, Coralie Poncet, Ross L. Prentice, Nadege Presneau, Renate Prevos, Katri Pylkäs, Paolo Radice, Gad Rennert, Hedy S. Rennert, Atocha Romero, Emmanouil Saloustros, Elinor J. Sawyer, Rita K. Schmutzler, Lukas Schwentner, Christopher Scott, Mitul Shah, Chen Yang Shen, Xiao Ou Shu, Xueling Sim, Melissa C. Southey, Jennifer Stone, Daniel O. Stram, Rulla M. Tamimi, Soo Hwang Teo, Lauren R. Teras, Mary Beth Terry, Katarzyna Tomczyk, Ian Tomlinson, Melissa A. Troester, Thérèse Truong, Celine M. Vachon, Chantal Van Ongeval, Qin Wang, Barbara Wappenschmidt, Camilla Wendt, Robert Winqvist, Alicja Wolk, Anna H. Wu, Siddhartha Yadav, Cheng Har Yip, Wei Zheng, Argyrios Ziogas

Australian Centre For Precision Health

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

16 Citations (Scopus)

Abstract

PURPOSEA polygenic risk score (PRS) consisting of 313 common genetic variants (PRS313) is associated with risk of breast cancer and contralateral breast cancer. This study aimed to evaluate the association of the PRS313 with clinicopathologic characteristics of, and survival following, breast cancer.METHODSWomen with invasive breast cancer were included, 98,397 of European ancestry and 12,920 of Asian ancestry, from the Breast Cancer Association Consortium (BCAC), and 683 women from the European MINDACT trial. Associations between PRS313 and clinicopathologic characteristics, including the 70-gene signature for MINDACT, were evaluated using logistic regression analyses. Associations of PRS313 (continuous, per standard deviation) with overall survival (OS) and breast cancer specific survival (BCSS) were evaluated with Cox regression, adjusted for clinicopathologic characteristics and treatment.RESULTSThe PRS313 was associated with more favorable tumor characteristics. In BCAC, increasing PRS313 was associated with lower grade, hormone receptor positive status, and smaller tumor size. In MINDACT, PRS313 was associated with a low risk 70-gene signature. In European women from BCAC, higher PRS313 was associated with better OS and BCSS: hazard ratio (HR) 0.96 (95% CI, 0.94 to 0.97) and 0.96 (95% CI, 0.94 to 0.98), but the association disappeared after adjustment for clinicopathologic characteristics (and treatment): OS HR, 1.01 (95% CI, 0.98 to 1.05) and BCSS HR, 1.02 (95% CI, 0.98 to 1.07). The results in MINDACT and Asian women from BCAC were consistent.CONCLUSIONAn increased PRS313 is associated with favorable tumor characteristics, but is not independently associated with prognosis. Thus, PRS313 has no role in the clinical management of primary breast cancer at the time of diagnosis. Nevertheless, breast cancer mortality rates will be higher for women with higher PRS313 as increasing PRS313 is associated with an increased risk of disease. This information is crucial for modeling effective stratified screening programs.

Original language	English
Pages (from-to)	1849-1863
Number of pages	15
Journal	Journal of Clinical Oncology
Volume	41
Issue number	10
DOIs	https://doi.org/10.1200/JCO.22.01978
Publication status	Published or Issued - 1 Apr 2023

ASJC Scopus subject areas

Oncology
Cancer Research

Access to Document

10.1200/JCO.22.01978

Cite this

Lopes Cardozo, J. M. N., Andrulis, I. L., Bojesen, S. E., Dörk, T., Eccles, D. M., Fasching, P. A., Hooning, M. J., Keeman, R., Nevanlinna, H., Rutgers, E. J. T., Easton, D. F., Hall, P., Pharoah, P. D. P., Van 't Veer, L. J., Schmidt, M. K., Ahearn, T. U., Anton-Culver, H., Arndt, V., Auer, P. L., ... Ziogas, A. (2023). Associations of a Breast Cancer Polygenic Risk Score With Tumor Characteristics and Survival. Journal of Clinical Oncology, 41(10), 1849-1863. https://doi.org/10.1200/JCO.22.01978

@article{6dd451cdf6cb454d930a68805217f90e,

title = "Associations of a Breast Cancer Polygenic Risk Score With Tumor Characteristics and Survival",

abstract = "PURPOSEA polygenic risk score (PRS) consisting of 313 common genetic variants (PRS313) is associated with risk of breast cancer and contralateral breast cancer. This study aimed to evaluate the association of the PRS313 with clinicopathologic characteristics of, and survival following, breast cancer.METHODSWomen with invasive breast cancer were included, 98,397 of European ancestry and 12,920 of Asian ancestry, from the Breast Cancer Association Consortium (BCAC), and 683 women from the European MINDACT trial. Associations between PRS313 and clinicopathologic characteristics, including the 70-gene signature for MINDACT, were evaluated using logistic regression analyses. Associations of PRS313 (continuous, per standard deviation) with overall survival (OS) and breast cancer specific survival (BCSS) were evaluated with Cox regression, adjusted for clinicopathologic characteristics and treatment.RESULTSThe PRS313 was associated with more favorable tumor characteristics. In BCAC, increasing PRS313 was associated with lower grade, hormone receptor positive status, and smaller tumor size. In MINDACT, PRS313 was associated with a low risk 70-gene signature. In European women from BCAC, higher PRS313 was associated with better OS and BCSS: hazard ratio (HR) 0.96 (95% CI, 0.94 to 0.97) and 0.96 (95% CI, 0.94 to 0.98), but the association disappeared after adjustment for clinicopathologic characteristics (and treatment): OS HR, 1.01 (95% CI, 0.98 to 1.05) and BCSS HR, 1.02 (95% CI, 0.98 to 1.07). The results in MINDACT and Asian women from BCAC were consistent.CONCLUSIONAn increased PRS313 is associated with favorable tumor characteristics, but is not independently associated with prognosis. Thus, PRS313 has no role in the clinical management of primary breast cancer at the time of diagnosis. Nevertheless, breast cancer mortality rates will be higher for women with higher PRS313 as increasing PRS313 is associated with an increased risk of disease. This information is crucial for modeling effective stratified screening programs.",

author = "{Lopes Cardozo}, {Josephine M.N.} and Andrulis, {Irene L.} and Bojesen, {Stig E.} and Thilo D{\"o}rk and Eccles, {Diana M.} and Fasching, {Peter A.} and Hooning, {Maartje J.} and Renske Keeman and Heli Nevanlinna and Rutgers, {Emiel J.T.} and Easton, {Douglas F.} and Per Hall and Pharoah, {Paul D.P.} and {Van 't Veer}, {Laura J.} and Schmidt, {Marjanka K.} and Ahearn, {Thomas U.} and Hoda Anton-Culver and Volker Arndt and Auer, {Paul L.} and Annelie Augustinsson and {Beane Freeman}, {Laura E.} and Heiko Becher and Beckmann, {Matthias W.} and Sabine Behrens and Javier Benitez and Marina Bermisheva and Carl Blomqvist and Bolla, {Manjeet K.} and Bernardo Bonanni and Terry Boyle and Hermann Brenner and Brucker, {Sara Y.} and Thomas Br{\"u}ning and Barbara Burwinkel and Buys, {Saundra S.} and Camp, {Nicola J.} and Federico Canzian and Fatima Cardoso and Castelao, {Jose E.} and Cessna, {Melissa H.} and Chan, {Tsun L.} and Jenny Chang-Claude and Georgia Chenevix-Trench and Choi, {Ji Yeob} and Colonna, {Sarah V.} and Ellen Copson and Couch, {Fergus J.} and Angela Cox and Cross, {Simon S.} and Kamila Czene and Daly, {Mary B.} and Joe Dennis and Peter Devilee and Drukker, {Caroline A.} and Dunning, {Alison M.} and Miriam Dwek and Eliassen, {A. Heather} and Christoph Engel and Evans, {D. Gareth} and Figueroa, {Jonine D.} and Olivia Fletcher and Henrik Flyger and Manuela Gago-Dominguez and Montserrat Garc{\'i}a-Closas and Garc{\'i}a-S{\'a}enz, {Jos{\'e} A.} and Jeanine Genkinger and Giles, {Graham G.} and Anna Gonz{\'a}lez-Neira and Pascal Gu{\'e}nel and Melanie G{\"u}ndert and Eric Hahnen and Haiman, {Christopher A.} and Niclas H{\aa}kansson and Ute Hamann and Mikael Hartman and Heemskerk-Gerritsen, {Bernadette A.M.} and Alexander Hein and Ho, {Weang Kee} and Reiner Hoppe and Hopper, {John L.} and Houlston, {Richard S.} and Anthony Howell and Hunter, {David J.} and Hidemi Ito and Anna Jakubowska and Helena Jernstr{\"o}m and John, {Esther M.} and Nichola Johnson and Jones, {Michael E.} and Vijai Joseph and Rudolf Kaaks and Daehee Kang and Kim, {Sung Won} and Kitahara, {Cari M.} and Koppert, {Linetta B.} and Kosma, {Veli Matti} and Peter Kraft and Kristensen, {Vessela N.} and Katerina Kubelka-Sabit and Stella Koutros and Kurian, {Allison W.} and Ava Kwong and Lacey, {James V.} and Diether Lambrechts and {Le Marchand}, Loic and Jingmei Li and Jan Lubi{\'n}ski and Michael Lush and Arto Mannermaa and Mehdi Manoochehri and Sara Margolin and Keitaro Matsuo and Dimitrios Mavroudis and Kyriaki Michailidou and Milne, {Roger L.} and {Mohd Taib}, {Nur Aishah} and Mulligan, {Anna Marie} and Patrick Neven and Newman, {William G.} and Nadia Obi and Kenneth Offit and Olshan, {Andrew F.} and Park, {Sue K.} and Park-Simon, {Tjoung Won} and Patel, {Alpa V.} and Dijana Plaseska-Karanfilska and Coralie Poncet and Prentice, {Ross L.} and Nadege Presneau and Renate Prevos and Katri Pylk{\"a}s and Paolo Radice and Gad Rennert and Rennert, {Hedy S.} and Atocha Romero and Emmanouil Saloustros and Sawyer, {Elinor J.} and Schmutzler, {Rita K.} and Lukas Schwentner and Christopher Scott and Mitul Shah and Shen, {Chen Yang} and Shu, {Xiao Ou} and Xueling Sim and Southey, {Melissa C.} and Jennifer Stone and Stram, {Daniel O.} and Tamimi, {Rulla M.} and Teo, {Soo Hwang} and Teras, {Lauren R.} and Terry, {Mary Beth} and Katarzyna Tomczyk and Ian Tomlinson and Troester, {Melissa A.} and Th{\'e}r{\`e}se Truong and Vachon, {Celine M.} and {Van Ongeval}, Chantal and Qin Wang and Barbara Wappenschmidt and Camilla Wendt and Robert Winqvist and Alicja Wolk and Wu, {Anna H.} and Siddhartha Yadav and Yip, {Cheng Har} and Wei Zheng and Argyrios Ziogas",

note = "Publisher Copyright: {\textcopyright} 2023 American Society of Clinical Oncology.",

year = "2023",

month = apr,

day = "1",

doi = "10.1200/JCO.22.01978",

language = "English",

volume = "41",

pages = "1849--1863",

journal = "Journal of Clinical Oncology",

issn = "0732-183X",

publisher = "Lippincott Williams and Wilkins",

number = "10",

}

Lopes Cardozo, JMN, Andrulis, IL, Bojesen, SE, Dörk, T, Eccles, DM, Fasching, PA, Hooning, MJ, Keeman, R, Nevanlinna, H, Rutgers, EJT, Easton, DF, Hall, P, Pharoah, PDP, Van 't Veer, LJ, Schmidt, MK, Ahearn, TU, Anton-Culver, H, Arndt, V, Auer, PL, Augustinsson, A, Beane Freeman, LE, Becher, H, Beckmann, MW, Behrens, S, Benitez, J, Bermisheva, M, Blomqvist, C, Bolla, MK, Bonanni, B, Boyle, T, Brenner, H, Brucker, SY, Brüning, T, Burwinkel, B, Buys, SS, Camp, NJ, Canzian, F, Cardoso, F, Castelao, JE, Cessna, MH, Chan, TL, Chang-Claude, J, Chenevix-Trench, G, Choi, JY, Colonna, SV, Copson, E, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, Dennis, J, Devilee, P, Drukker, CA, Dunning, AM, Dwek, M, Eliassen, AH, Engel, C, Evans, DG, Figueroa, JD, Fletcher, O, Flyger, H, Gago-Dominguez, M, García-Closas, M, García-Sáenz, JA, Genkinger, J, Giles, GG, González-Neira, A, Guénel, P, Gündert, M, Hahnen, E, Haiman, CA, Håkansson, N, Hamann, U, Hartman, M, Heemskerk-Gerritsen, BAM, Hein, A, Ho, WK, Hoppe, R, Hopper, JL, Houlston, RS, Howell, A, Hunter, DJ, Ito, H, Jakubowska, A, Jernström, H, John, EM, Johnson, N, Jones, ME, Joseph, V, Kaaks, R, Kang, D, Kim, SW, Kitahara, CM, Koppert, LB, Kosma, VM, Kraft, P, Kristensen, VN, Kubelka-Sabit, K, Koutros, S, Kurian, AW, Kwong, A, Lacey, JV, Lambrechts, D, Le Marchand, L, Li, J, Lubiński, J, Lush, M, Mannermaa, A, Manoochehri, M, Margolin, S, Matsuo, K, Mavroudis, D, Michailidou, K, Milne, RL, Mohd Taib, NA, Mulligan, AM, Neven, P, Newman, WG, Obi, N, Offit, K, Olshan, AF, Park, SK, Park-Simon, TW, Patel, AV, Plaseska-Karanfilska, D, Poncet, C, Prentice, RL, Presneau, N, Prevos, R, Pylkäs, K, Radice, P, Rennert, G, Rennert, HS, Romero, A, Saloustros, E, Sawyer, EJ, Schmutzler, RK, Schwentner, L, Scott, C, Shah, M, Shen, CY, Shu, XO, Sim, X, Southey, MC, Stone, J, Stram, DO, Tamimi, RM, Teo, SH, Teras, LR, Terry, MB, Tomczyk, K, Tomlinson, I, Troester, MA, Truong, T, Vachon, CM, Van Ongeval, C, Wang, Q, Wappenschmidt, B, Wendt, C, Winqvist, R, Wolk, A, Wu, AH, Yadav, S, Yip, CH, Zheng, W & Ziogas, A 2023, 'Associations of a Breast Cancer Polygenic Risk Score With Tumor Characteristics and Survival', Journal of Clinical Oncology, vol. 41, no. 10, pp. 1849-1863. https://doi.org/10.1200/JCO.22.01978

TY - JOUR

T1 - Associations of a Breast Cancer Polygenic Risk Score With Tumor Characteristics and Survival

AU - Lopes Cardozo, Josephine M.N.

AU - Andrulis, Irene L.

AU - Bojesen, Stig E.

AU - Dörk, Thilo

AU - Eccles, Diana M.

AU - Fasching, Peter A.

AU - Hooning, Maartje J.

AU - Keeman, Renske

AU - Nevanlinna, Heli

AU - Rutgers, Emiel J.T.

AU - Easton, Douglas F.

AU - Hall, Per

AU - Pharoah, Paul D.P.

AU - Van 't Veer, Laura J.

AU - Schmidt, Marjanka K.

AU - Ahearn, Thomas U.

AU - Anton-Culver, Hoda

AU - Arndt, Volker

AU - Auer, Paul L.

AU - Augustinsson, Annelie

AU - Beane Freeman, Laura E.

AU - Becher, Heiko

AU - Beckmann, Matthias W.

AU - Behrens, Sabine

AU - Benitez, Javier

AU - Bermisheva, Marina

AU - Blomqvist, Carl

AU - Bolla, Manjeet K.

AU - Bonanni, Bernardo

AU - Boyle, Terry

AU - Brenner, Hermann

AU - Brucker, Sara Y.

AU - Brüning, Thomas

AU - Burwinkel, Barbara

AU - Buys, Saundra S.

AU - Camp, Nicola J.

AU - Canzian, Federico

AU - Cardoso, Fatima

AU - Castelao, Jose E.

AU - Cessna, Melissa H.

AU - Chan, Tsun L.

AU - Chang-Claude, Jenny

AU - Chenevix-Trench, Georgia

AU - Choi, Ji Yeob

AU - Colonna, Sarah V.

AU - Copson, Ellen

AU - Couch, Fergus J.

AU - Cox, Angela

AU - Cross, Simon S.

AU - Czene, Kamila

AU - Daly, Mary B.

AU - Dennis, Joe

AU - Devilee, Peter

AU - Drukker, Caroline A.

AU - Dunning, Alison M.

AU - Dwek, Miriam

AU - Eliassen, A. Heather

AU - Engel, Christoph

AU - Evans, D. Gareth

AU - Figueroa, Jonine D.

AU - Fletcher, Olivia

AU - Flyger, Henrik

AU - Gago-Dominguez, Manuela

AU - García-Closas, Montserrat

AU - García-Sáenz, José A.

AU - Genkinger, Jeanine

AU - Giles, Graham G.

AU - González-Neira, Anna

AU - Guénel, Pascal

AU - Gündert, Melanie

AU - Hahnen, Eric

AU - Haiman, Christopher A.

AU - Håkansson, Niclas

AU - Hamann, Ute

AU - Hartman, Mikael

AU - Heemskerk-Gerritsen, Bernadette A.M.

AU - Hein, Alexander

AU - Ho, Weang Kee

AU - Hoppe, Reiner

AU - Hopper, John L.

AU - Houlston, Richard S.

AU - Howell, Anthony

AU - Hunter, David J.

AU - Ito, Hidemi

AU - Jakubowska, Anna

AU - Jernström, Helena

AU - John, Esther M.

AU - Johnson, Nichola

AU - Jones, Michael E.

AU - Joseph, Vijai

AU - Kaaks, Rudolf

AU - Kang, Daehee

AU - Kim, Sung Won

AU - Kitahara, Cari M.

AU - Koppert, Linetta B.

AU - Kosma, Veli Matti

AU - Kraft, Peter

AU - Kristensen, Vessela N.

AU - Kubelka-Sabit, Katerina

AU - Koutros, Stella

AU - Kurian, Allison W.

AU - Kwong, Ava

AU - Lacey, James V.

AU - Lambrechts, Diether

AU - Le Marchand, Loic

AU - Li, Jingmei

AU - Lubiński, Jan

AU - Lush, Michael

AU - Mannermaa, Arto

AU - Manoochehri, Mehdi

AU - Margolin, Sara

AU - Matsuo, Keitaro

AU - Mavroudis, Dimitrios

AU - Michailidou, Kyriaki

AU - Milne, Roger L.

AU - Mohd Taib, Nur Aishah

AU - Mulligan, Anna Marie

AU - Neven, Patrick

AU - Newman, William G.

AU - Obi, Nadia

AU - Offit, Kenneth

AU - Olshan, Andrew F.

AU - Park, Sue K.

AU - Park-Simon, Tjoung Won

AU - Patel, Alpa V.

AU - Plaseska-Karanfilska, Dijana

AU - Poncet, Coralie

AU - Prentice, Ross L.

AU - Presneau, Nadege

AU - Prevos, Renate

AU - Pylkäs, Katri

AU - Radice, Paolo

AU - Rennert, Gad

AU - Rennert, Hedy S.

AU - Romero, Atocha

AU - Saloustros, Emmanouil

AU - Sawyer, Elinor J.

AU - Schmutzler, Rita K.

AU - Schwentner, Lukas

AU - Scott, Christopher

AU - Shah, Mitul

AU - Shen, Chen Yang

AU - Shu, Xiao Ou

AU - Sim, Xueling

AU - Southey, Melissa C.

AU - Stone, Jennifer

AU - Stram, Daniel O.

AU - Tamimi, Rulla M.

AU - Teo, Soo Hwang

AU - Teras, Lauren R.

AU - Terry, Mary Beth

AU - Tomczyk, Katarzyna

AU - Tomlinson, Ian

AU - Troester, Melissa A.

AU - Truong, Thérèse

AU - Vachon, Celine M.

AU - Van Ongeval, Chantal

AU - Wang, Qin

AU - Wappenschmidt, Barbara

AU - Wendt, Camilla

AU - Winqvist, Robert

AU - Wolk, Alicja

AU - Wu, Anna H.

AU - Yadav, Siddhartha

AU - Yip, Cheng Har

AU - Zheng, Wei

AU - Ziogas, Argyrios

PY - 2023/4/1

Y1 - 2023/4/1

N2 - PURPOSEA polygenic risk score (PRS) consisting of 313 common genetic variants (PRS313) is associated with risk of breast cancer and contralateral breast cancer. This study aimed to evaluate the association of the PRS313 with clinicopathologic characteristics of, and survival following, breast cancer.METHODSWomen with invasive breast cancer were included, 98,397 of European ancestry and 12,920 of Asian ancestry, from the Breast Cancer Association Consortium (BCAC), and 683 women from the European MINDACT trial. Associations between PRS313 and clinicopathologic characteristics, including the 70-gene signature for MINDACT, were evaluated using logistic regression analyses. Associations of PRS313 (continuous, per standard deviation) with overall survival (OS) and breast cancer specific survival (BCSS) were evaluated with Cox regression, adjusted for clinicopathologic characteristics and treatment.RESULTSThe PRS313 was associated with more favorable tumor characteristics. In BCAC, increasing PRS313 was associated with lower grade, hormone receptor positive status, and smaller tumor size. In MINDACT, PRS313 was associated with a low risk 70-gene signature. In European women from BCAC, higher PRS313 was associated with better OS and BCSS: hazard ratio (HR) 0.96 (95% CI, 0.94 to 0.97) and 0.96 (95% CI, 0.94 to 0.98), but the association disappeared after adjustment for clinicopathologic characteristics (and treatment): OS HR, 1.01 (95% CI, 0.98 to 1.05) and BCSS HR, 1.02 (95% CI, 0.98 to 1.07). The results in MINDACT and Asian women from BCAC were consistent.CONCLUSIONAn increased PRS313 is associated with favorable tumor characteristics, but is not independently associated with prognosis. Thus, PRS313 has no role in the clinical management of primary breast cancer at the time of diagnosis. Nevertheless, breast cancer mortality rates will be higher for women with higher PRS313 as increasing PRS313 is associated with an increased risk of disease. This information is crucial for modeling effective stratified screening programs.

AB - PURPOSEA polygenic risk score (PRS) consisting of 313 common genetic variants (PRS313) is associated with risk of breast cancer and contralateral breast cancer. This study aimed to evaluate the association of the PRS313 with clinicopathologic characteristics of, and survival following, breast cancer.METHODSWomen with invasive breast cancer were included, 98,397 of European ancestry and 12,920 of Asian ancestry, from the Breast Cancer Association Consortium (BCAC), and 683 women from the European MINDACT trial. Associations between PRS313 and clinicopathologic characteristics, including the 70-gene signature for MINDACT, were evaluated using logistic regression analyses. Associations of PRS313 (continuous, per standard deviation) with overall survival (OS) and breast cancer specific survival (BCSS) were evaluated with Cox regression, adjusted for clinicopathologic characteristics and treatment.RESULTSThe PRS313 was associated with more favorable tumor characteristics. In BCAC, increasing PRS313 was associated with lower grade, hormone receptor positive status, and smaller tumor size. In MINDACT, PRS313 was associated with a low risk 70-gene signature. In European women from BCAC, higher PRS313 was associated with better OS and BCSS: hazard ratio (HR) 0.96 (95% CI, 0.94 to 0.97) and 0.96 (95% CI, 0.94 to 0.98), but the association disappeared after adjustment for clinicopathologic characteristics (and treatment): OS HR, 1.01 (95% CI, 0.98 to 1.05) and BCSS HR, 1.02 (95% CI, 0.98 to 1.07). The results in MINDACT and Asian women from BCAC were consistent.CONCLUSIONAn increased PRS313 is associated with favorable tumor characteristics, but is not independently associated with prognosis. Thus, PRS313 has no role in the clinical management of primary breast cancer at the time of diagnosis. Nevertheless, breast cancer mortality rates will be higher for women with higher PRS313 as increasing PRS313 is associated with an increased risk of disease. This information is crucial for modeling effective stratified screening programs.

UR - http://www.scopus.com/inward/record.url?scp=85151313050&partnerID=8YFLogxK

U2 - 10.1200/JCO.22.01978

DO - 10.1200/JCO.22.01978

M3 - Article

C2 - 36689693

AN - SCOPUS:85151313050

SN - 0732-183X

VL - 41

SP - 1849

EP - 1863

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

IS - 10

ER -

Associations of a Breast Cancer Polygenic Risk Score With Tumor Characteristics and Survival

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