Comprehensive Inherited Risk Estimation for Risk-Based Breast Cancer Screening in Women
Nina Mars(Broad Institute), Sini Kerminen(University of Helsinki), Max Tamlander(University of Helsinki), Matti Pirinen(University of Helsinki), Eveliina Jakkula(University of Helsinki), Kirsimari Aaltonen(University of Helsinki), Tuomo J Meretoja(University of Helsinki), Sirpa Heinävaara(University of Helsinki), Elisabeth Widén(University of Helsinki), Samuli Ripatti(Broad Institute), Aarno Palotie, Mark J. Daly, Bridget Riley-Gills, Howard J. Jacob, Dirk S. Paul, Athena Matakidou, Adam Platt, Heiko Runz, Sally John, George Okafo, Nathan Lawless, Robert M. Plenge, Joseph Maranville, Mark I. McCarthy, Julie Hunkapiller, Margaret G. Ehm, Kirsi Auro(University of Helsinki), Simonne Longerich, Caroline S. Fox, Anders Mälarstig, K. Klinger, Deepak Raipal, Eric Green, Robert Graham, Robert Yang, Chris O’Donnell, Tomi P. Mäkelä, Jaakko Kaprio, Petri Virolainen, Antti Hakanen, Terhi Kilpi, Markus Perola, Jukka Partanen, Anne Pitkäranta, Juhani Junttila, Raisa Serpi, Tarja Laitinen, Veli‐Matti Kosma, Jari A. Laukkanen, Marco Hautalahti, Outi Tuovila, Raimo Pakkanen, Jeffrey F. Waring, Bridget Riley‐Gillis, Fedik Rahimov, Ioanna Tachmazidou, Chia‐Yen Chen, Heiko Runz, Zhihao Ding, Marc Jung, Shameek Biswas, Rion Pendergrass, Julie Hunkapiller, Margaret G. Ehm, David Pulford, Neha Raghavan, Adriana Huertas‐Vázquez, Jae-Hoon Sul, Anders Mälarstig, Xinli Hu, K. Klinger, Robert Graham, Eric Green, Sahar V. Mozaffari, Dawn Waterworth, Nicole Renaud, Ma’en Obeidat, Samuli Ripatti(Broad Institute), Johanna Schleutker, Markus Perola, Mikko Arvas, Olli Carpén, Reetta Hinttala, Johannes Kettunen, Arto Mannermaa, Katriina Aalto‐Setälä, Mika Kähönen, Jari A. Laukkanen, Johanna Mäkelä, Reetta Kälviäinen, Valtteri Julkunen, Hilkka Soininen, Anne M. Remes, Mikko Hiltunen, Jukka Peltola, Minna Raivio, Pentti Tienari, Juha O. Rinne, Roosa Kallionpää, Juulia Partanen, Ali Abbasi, Adam Ziemann, Nizar Smaoui, Anne Lehtonen, Susan Eaton, Heiko Runz, Sanni Lahdenperä, Shameek Biswas, Julie Hunkapiller, Natalie Bowers, Edmond Teng, Rion Pendergrass, Fanli Xu, David Pulford, Kirsi Auro(University of Helsinki), Laura Addis, John D. Eicher, Qingqin S. Li(Broad Institute), Karen He(University of Helsinki), Ekaterina Khramtsova, Neha Raghavan, Martti Färkkilâ, Jukka Koskela, Sampsa Pikkarainen, Airi Jussila, Katri Kaukinen, Timo Blomster, Mikko Kiviniemi, Markku Voutilainen, Mark J. Daly, Ali Abbasi, Jeffrey F. Waring, Nizar Smaoui, Fedik Rahimov, Anne Lehtonen, Tim Lu, Natalie Bowers, Rion Pendergrass, Linda McCarthy, Amy Hart, Meijian Guan, Jason E. Miller, Kirsi Kalpala(University of Helsinki), Melissa Miller, Xinli Hu, Kari K. Eklund, Antti Palomäki, Pia Isomäki, Laura Pirilä, Oili Kaipiainen‐Seppänen, Johanna Huhtakangas, Nina Mars(Broad Institute), Ali Abbasi, Jeffrey F. Waring, Fedik Rahimov, Apinya Lertratanakul, Nizar Smaoui, Anne Lehtonen, David A. Close, Marla Hochfeld, Natalie Bowers, Rion Pendergrass, Jorge Esparza Gordillo, Kirsi Auro(University of Helsinki), Dawn Waterworth, Fabiana Farias, Kirsi Kalpala(University of Helsinki), Nan Bing, Xinli Hu, Tarja Laitinen, Margit Pelkonen, Paula Kauppi, Hannu Kankaanranta, Terttu Harju, Riitta Lahesmaa, Nizar Smaoui, Alex Mackay, Glenda Lassi, Susan Eaton, Hubert Chen, Rion Pendergrass, Natalie Bowers, Joanna Betts, Kirsi Auro(University of Helsinki), Rajashree Mishra, Majd Mouded, Debby Ngo, Teemu Niiranen, Felix Vaura, Veikko Salomaa, Kaj Metsärinne, Jenni Aittokallio, Mika Kähönen, Jussi Hernesniemi, Daniel Gordin, Juha Sinisalo, Marja‐Riitta Taskinen, Tiinamaija Tuomi, Timo P. Hiltunen, Jari A. Laukkanen, Amanda Elliott, Mary Pat Reeve, Sanni Ruotsalainen, Benjamin Challis, Dirk S. Paul, Julie Hunkapiller, Natalie Bowers, Rion Pendergrass, Audrey Y. Chu, Kirsi Auro(University of Helsinki), Dermot F. Reilly, Mike Mendelson, Jaakko Parkkinen, Melissa Miller, Tuomo J Meretoja(University of Helsinki), Heikki Joensuu, Olli Carpén, Johanna Mattson, Eveliina Salminen(University of Helsinki), Annika Auranen, Peeter Karihtala, Päivi Auvinen, Klaus Elenius, Johanna Schleutker, Esa Pitkänen, Nina Mars(Broad Institute), Mark J. Daly, Relja Popovic, Jeffrey F. Waring, Bridget Riley‐Gillis, Anne Lehtonen, Jennifer L. Schutzman, Julie Hunkapiller, Natalie Bowers, Rion Pendergrass, Diptee Kulkarni, Kirsi Auro(University of Helsinki), Alessandro Porello, Andrey Loboda, Heli Lehtonen, Stefan McDonough, Sauli Vuoti, Kai Kaarniranta, Joni A. Turunen, Terhi Ollila, Hannu Uusitalo, Juha Karjalainen, Esa Pitkänen, Mengzhen Liu, Heiko Runz, Stephanie Loomis, Erich C. Strauss, Natalie Bowers, Hao Chen, Rion Pendergrass, Kaisa Tasanen, Laura Huilaja, Katariina Hannula‐Jouppi, Teea Salmi, Sirkku Peltonen, Leena Koulu, Nizar Smaoui, Fedik Rahimov, Anne Lehtonen, David F. Choy, Rion Pendergrass, Dawn Waterworth, Kirsi Kalpala(University of Helsinki), Ying Wu, Pirkko J. Pussinen, Aino Salminen, Tuula Salo, David Rice, Pekka Nieminen, Ulla Palotie, Maria Siponen(University of Helsinki), Liisa Suominen, Päivi Mäntylä, Ulvi Kahraman Gürsoy, Vuokko Anttonen, Kirsi Sipilä(University of Helsinki), Rion Pendergrass, Hannele Laivuori, Venla Kurra, Laura Kotaniemi‐Talonen, Oskari Heikinheimo, Ilkka Kalliala, Lauri A. Aaltonen(University of Helsinki), Varpu Jokimaa, Johannes Kettunen, Marja Vääräsmäki, Outi Uimari, Laure Morin‐Papunen, Maarit Niinimäki, Terhi Piltonen, Katja Kivinen, Elisabeth Widén(University of Helsinki), Taru Tukiainen, Mary Pat Reeve, Mark J. Daly, Niko Välimäki, Eija K. Laakkonen, Jaakko Tyrmi, Heidi Silven, Eeva Sliz, Riikka K. Arffman, Susanna Savukoski, Triin Laisk, Natalia Pujol, Mengzhen Liu, Bridget Riley‐Gillis, Rion Pendergrass, Janet Kumar, Kirsi Auro(University of Helsinki), Iiris Hovatta, Chia‐Yen Chen, Erkki Isometsä, Kumar Veerapen, Hanna M. Ollila, Jaana Suvisaari, Thomas D. Als, Antti Mäkitie, Argyro Bizaki-Vallaskangas, Sanna Toppila‐Salmi, Tytti Willberg, Elmo Saarentaus, Antti A. Aarnisalo, Eveliina Salminen(University of Helsinki), Elisa Rahikkala(University of Helsinki), Johannes Kettunen, Kristiina Aittomäki, Fredrik Åberg, Mitja Kurki, Samuli Ripatti(Broad Institute), Mark J. Daly, Juha Karjalainen, Aki S. Havulinna, Juha Mehtonen, Priit Palta, Shabbeer Hassan, Pietro Della Briotta Parolo, Wei Zhou, Mutaamba Maasha, Kumar Veerapen, Shabbeer Hassan, Susanna Lemmelä, Manuel A. Rivas, Mari Niemi, Aarno Palotie, Aoxing Liu, Arto Lehistö, Andrea Ganna, Vincent Llorens, Hannele Laivuori, Taru Tukiainen, Mary Pat Reeve, Henrike Heyne, Nina Mars(Broad Institute), Joel Rämö, Elmo Saarentaus, Hanna M. Ollila, Rodos Rodosthenous, Satu Strausz, Tuula Palotie, Kimmo Palin, Javier Gracia‐Tabuenca, Harri Siirtola, Tuomo Kiiskinen(University of Helsinki), Jiwoo Lee, Kristin Tsuo, Amanda Elliott, Kati Kristiansson, Mikko Arvas, Kati Hyvärinen, Jarmo Ritari, Olli Carpén, Johannes Kettunen, Katri Pylkäs, Eeva Sliz, Minna K. Karjalainen, Tuomo Mantere(University of Helsinki), Eeva Kangasniemi, Sami Heikkinen, Arto Mannermaa, Eija K. Laakkonen, Nina Pitkänen(Broad Institute), Samuel Lessard, Clément Chatelain, Perttu Terho, Sirpa Soini(University of Helsinki), Jukka Partanen, Eero Punkka, Raisa Serpi, Sanna Siltanen, Veli‐Matti Kosma, Teijo Kuopio, Anu Jalanko, Huei-Yi Shen, Risto Kajanne, Mervi Aavikko, Mitja Kurki, Juha Karjalainen, Pietro Della Briotta Parolo, Arto Lehistö, Juha Mehtonen, Wei Zhou, Masahiro Kanai, Mutaamba Maasha, Kumar Veerapen, Hannele Laivuori, Aki S. Havulinna, Susanna Lemmelä, Tuomo Kiiskinen(University of Helsinki), L. Elisa Lahtela, Mari Kaunisto(University of Helsinki), Elina Kilpeläinen, Timo P. Sipilä, Oluwaseun Alexander Dada, Awaisa Ghazal, Anastasia Kytölä, Rigbe Weldatsadik, Kati Donner, Timo P. Sipilä, Anu Loukola, Päivi Laiho, Tuuli Sistonen, Essi Kaiharju, Markku Laukkanen, Elina Järvensivu, Sini Lähteenmäki(University of Helsinki), Lotta Männikkö, Regis Wong, Auli Toivola, Minna Brunfeldt, Hannele Mattsson, Kati Kristiansson, Susanna Lemmelä, Sami Koskelainen, Tero Hiekkalinna, Teemu Paajanen, Priit Palta, Kalle Pärn, Mart Kals, Shuang Luo, Vishal Sinha, Tarja Laitinen, Mary Pat Reeve, Marianna Niemi, Kumar Veerapen, Harri Siirtola, Javier Gracia‐Tabuenca, Mika Helminen, Tiina Luukkaala, Iida Vähätalo, Jyrki Pitkänen, Marco Hautalahti, Johanna Mäkelä, Sarah Smith, Tom Southerington
Cited by 31Open Access
Abstract
PURPOSE Family history (FH) and pathogenic variants (PVs) are used for guiding risk surveillance in selected high-risk women but little is known about their impact for breast cancer screening on population level. In addition, polygenic risk scores (PRSs) have been shown to efficiently stratify breast cancer risk through combining information about common genetic factors into one measure. METHODS In longitudinal real-life data, we evaluate PRS, FH, and PVs for stratified screening. Using FinnGen (N = 117,252), linked to the Mass Screening Registry for breast cancer (1992-2019; nationwide organized biennial screening for age 50-69 years), we assessed the screening performance of a breast cancer PRS and compared its performance with FH of breast cancer and PVs in moderate- ( CHEK2 )- to high-risk ( PALB2 ) susceptibility genes. RESULTS Effect sizes for FH, PVs, and high PRS (>90th percentile) were comparable in screening-aged women, with similar implications for shifting age at screening onset. A high PRS identified women more likely to be diagnosed with breast cancer after a positive screening finding (positive predictive value [PPV], 39.5% [95% CI, 37.6 to 41.5]). Combinations of risk factors increased the PPVs up to 45% to 50%. A high PRS conferred an elevated risk of interval breast cancer (hazard ratio [HR], 2.78 [95% CI, 2.00 to 3.86] at age 50 years; HR, 2.48 [95% CI, 1.67 to 3.70] at age 60 years), and women with a low PRS (<10th percentile) had a low risk for both interval- and screen-detected breast cancers. CONCLUSION Using real-life screening data, this study demonstrates the effectiveness of a breast cancer PRS for risk stratification, alone and combined with FH and PVs. Further research is required to evaluate their impact in a prospective risk-stratified screening program, including cost-effectiveness.
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