| Title: |
Overlap of high-risk individuals across family history, genetic & non-genetic breast cancer risk models: Analysis of 180,398 women from European & Asian ancestries. |
| Authors: |
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 |
| Source: |
medRxiv |
| Publication Year: |
2025 |
| Subject Terms: |
BRCA1; BRCA2; Breast cancer; Ductal Carcinoma In Situ (DCIS); Gail model; Polygenic risk score (PRS); Risk stratification; risk-based screening |
| Description: |
BACKGROUND: Breast cancer is multifactorial. Focusing on limited risk factors may miss high-risk individuals. 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 ( |
| Document Type: |
report |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://lirias.kuleuven.be/handle/20.500.12942/762048; https://doi.org/10.1101/2025.02.27.25323002; https://pubmed.ncbi.nlm.nih.gov/40093266 |
| DOI: |
10.1101/2025.02.27.25323002 |
| Availability: |
https://lirias.kuleuven.be/handle/20.500.12942/762048; https://hdl.handle.net/20.500.12942/762048; https://lirias.kuleuven.be/retrieve/48ba57e3-3acf-4b45-8cbf-a966af828069; https://doi.org/10.1101/2025.02.27.25323002; https://pubmed.ncbi.nlm.nih.gov/40093266 |
| Rights: |
info:eu-repo/semantics/openAccess ; public ; https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.509F9A39 |
| Database: |
BASE |