American journal of human genetics · 2020

Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk.

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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, NBCS Collaborators, 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, Fasching Peter A, Flyger Henrik, Gago-Dominguez Manuela, García-Closas Montserrat, García-Sáenz José A, Giles Graham G, Goldgar David E, González-Neira Anna, Haiman Christopher A, Håkansson Niclas, Hamann Ute, Hartman Mikael, Heemskerk-Gerritsen Bernadette A M, Hollestelle Antoinette, Hopper John L, Hou Ming-Feng, Howell Anthony, ABCTB Investigators, kConFab Investigators, Ito Hidemi, Jakimovska Milena, Jakubowska Anna, Janni Wolfgang, John Esther M, Jung Audrey, Kang Daehee, Kets C Marleen, Khusnutdinova Elza, Ko Yon-Dschun, Kristensen Vessela N, Kurian Allison W, Kwong Ava, Lambrechts Diether, Le Marchand Loic, Li Jingmei, Lindblom Annika, Lubiński Jan, Mannermaa Arto, Manoochehri Mehdi, Margolin Sara, Matsuo Keitaro, Mavroudis Dimitrios, Meindl Alfons, Milne Roger L, Mulligan Anna Marie, Muranen Taru A, Neuhausen Susan L, Nevanlinna Heli, Newman William G, Olshan Andrew F, Olson Janet E, Olsson Håkan, Park-Simon Tjoung-Won, Peto Julian, Petridis Christos, Plaseska-Karanfilska Dijana, Presneau Nadege, Pylkäs Katri, Radice Paolo, Rennert Gad, Romero Atocha, Roylance Rebecca, Saloustros Emmanouil, Sawyer Elinor J, Schmutzler Rita K, Schwentner Lukas, Scott Christopher, See Mee-Hoong, Shah Mitul, Shen Chen-Yang, Shu Xiao-Ou, Siesling Sabine, Slager Susan, Sohn Christof, Southey Melissa C, Spinelli John J, Stone Jennifer, Tapper William J, Tengström Maria, Teo Soo Hwang, Terry Mary Beth, Tollenaar Rob A E M, Tomlinson Ian, Troester Melissa A, Vachon Celine M, van Ongeval Chantal, van Veen Elke M, Winqvist Robert, Wolk Alicja, Zheng Wei, Ziogas Argyrios, Easton Douglas F, Hall Per, Schmidt Marjanka K

Аннотация

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.

Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk.

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