Overlap of high-risk individuals across family history, genetic & non-genetic breast cancer risk models: Analysis of 180,398 women from European & Asian ancestries.
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Ho Peh Joo, Loo Christine Kim Yan, Goh Meng Huang, Abubakar Mustapha, Ahearn Thomas U, Andrulis Irene L, Antonenkova Natalia N, Aronson Kristan J, Augustinsson Annelie, Behrens Sabine, Bodelon Clara, Bogdanova Natalia V, Bolla Manjeet K, Brantley Kristen, Brenner Hermann, Byers Helen, Camp Nicola J, Castelao Jose E, Cessna Melissa H, Chang-Claude Jenny, Chanock Stephen J, Chenevix-Trench Georgia, Choi Ji-Yeob, Colonna Sarah V, Czene Kamila, Daly Mary B, Derouane Francoise, Dörk Thilo, Eliassen A Heather, Engel Christoph, Eriksson Mikael, Evans D Gareth, Fletcher Olivia, Fritschi Lin, Gago-Dominguez Manuela, Genkinger Jeanine M, Geurts-Giele Willemina R R, Glendon Gord, Hall Per, Hamann Ute, Ho Cecilia Y S, Ho Weang-Kee, Hooning Maartje J, Hoppe Reiner, Howell Anthony, Humphreys Keith, ABCTB Investigators, kConFab Investigators, SGBCC Investigators, MyBrCa Investigators, Ito Hidemi, Iwasaki Motoki, Jakubowska Anna, Jernström Helena, John Esther M, Johnson Nichola, Kang Daehee, Kim Sung-Won, Kitahara Cari M, Ko Yon-Dschun, Kraft Peter, Kwong Ava, Lambrechts Diether, Larsson Susanna, Li Shuai, Lindblom Annika, Linet Martha, Lissowska Jolanta, Lophatananon Artitaya, MacInnis Robert J, Mannermaa Arto, Manoukian Siranoush, Margolin Sara, Matsuo Keitaro, Michailidou Kyriaki, Milne Roger L, Taib Nur Aishah Mohd, Muir Kenneth, Murphy Rachel A, Newman William G, O'Brien Katie M, Obi Nadia, Olopade Olufunmilayo I, Panayiotidis Mihalis I, Park Sue K, Park-Simon Tjoung-Won, Patel Alpa V, Peterlongo Paolo, Plaseska-Karanfilska Dijana, Pylkäs Katri, Rashid Muhammad U, Rennert Gad, Rodriguez Juan, Saloustros Emmanouil, Sandler Dale P, Sawyer Elinor J, Scott Christopher G, Shahi Shamim, Shu Xiao-Ou, Shulman Katerina, Simard Jacques, Southey Melissa C, Stone Jennifer, Taylor Jack A, Teo Soo-Hwang, Teras Lauren R, Terry Mary Beth, Torres Diana, Vachon Celine M, Van Houdt Maxime, Verhoeven Jelle, Weinberg Clarice R, Wolk Alicja, Yamaji Taiki, Yip Cheng Har, Zheng Wei, Hartman Mikael, Li Jingmei
Аннотация
METHODS: We assessed the performance and overlap of various risk factors in identifying high-risk individuals for invasive breast cancer (BrCa) and ductal carcinoma in situ (DCIS) in 161,849 European-ancestry and 18,549 Asian-ancestry women. Discriminatory ability was evaluated using the area under the receiver operating characteristic curve (AUC). High-risk criteria included: 5-year absolute risk ≥1·66% by the Gail model [GAILbinary]; first-degree family history of breast cancer [FHbinary]; 5-year absolute risk ≥1·66% by a 313-variants polygenic risk score [PRSbinary]; and carriers of pathogenic variants in breast cancer predisposition genes [PTVbinary].
FINDINGS: The 5-year absolute risk by PRS outperformed the Gail model in predicting BrCa (Europeansvs controls: AUCPRS=0·635 [0·632-0·638] vs AUCGail=0·492 [0·489-0·495]; Asiansvs controls: AUCPRS=0·564 [0·556-0·573] vs AUCGail=0·506 [0·497-0·514]). PRSbinary and GAILbinary identified more high-risk European than Asia individuals. High-risk proportions were higher among BrCa (16-26%) and DCIS (20-33%) compared to controls (9-15%) among young Europeans and all Asians. Fewer than 7% of BrCa, 10% of DCIS, and 3% of controls were classified as high-risk by multiple risk classifiers. Overlap between PRSbinary and PTVbinary was minimal (<0·65% Europeans, <0·15% Asians) compared to the proportion at high risk using PTVbinary alone (Europeans: 4·6%, Asians: 4·4%) and PRSbinary alone (Europeans: 13·9%, Asians: 8·5%). PRSbinary and FHbinary uniquely identified 5-6% and 9-11% of young BrCa, respectively.
INTERPRETATION: The incomplete overlap between high-risk individuals identified by PRSbinary, GAILbinary, FHbinary, and PTVbinary highlights the need for a comprehensive approach to breast cancer risk prediction.