Alexandra J van den Broek1, Laura J van 't Veer1, Maartje J Hooning1, Sten Cornelissen1, Annegien Broeks1, Emiel J Rutgers1, Vincent T H B M Smit1, Cees J Cornelisse1, Mike van Beek1, Maryska L Janssen-Heijnen1, Caroline Seynaeve1, Pieter J Westenend1, Jan J Jobsen1, Sabine Siesling1, Rob A E M Tollenaar1, Flora E van Leeuwen1, Marjanka K Schmidt2. 1. Alexandra J. van den Broek, Laura J. van 't Veer, Sten Cornelissen, Annegien Broeks, Emiel J. Rutgers, Flora E. van Leeuwen, and Marjanka K. Schmidt, Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam; Maartje J. Hooning and Caroline Seynaeve, Erasmus MC Cancer Institute, Rotterdam; Vincent T.H.B.M. Smit, Cees J. Cornelisse, and Rob A.E.M. Tollenaar, Leiden University Medical Center, Leiden; Mike van Beek, PAMM, Catharina Hospital, Eindhoven; Maryska L. Janssen-Heijnen, Netherlands Comprehensive Cancer Organization, Eindhoven, and VieCuri Medical Centre, Venlo; Pieter J. Westenend, Laboratory for Pathology, Dordrecht; Jan J. Jobsen, Medisch Spectrum Twente, Enschede; and Sabine Sieling, Netherlands Comprehensive Cancer Organization, Utrecht, Netherlands. 2. Alexandra J. van den Broek, Laura J. van 't Veer, Sten Cornelissen, Annegien Broeks, Emiel J. Rutgers, Flora E. van Leeuwen, and Marjanka K. Schmidt, Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam; Maartje J. Hooning and Caroline Seynaeve, Erasmus MC Cancer Institute, Rotterdam; Vincent T.H.B.M. Smit, Cees J. Cornelisse, and Rob A.E.M. Tollenaar, Leiden University Medical Center, Leiden; Mike van Beek, PAMM, Catharina Hospital, Eindhoven; Maryska L. Janssen-Heijnen, Netherlands Comprehensive Cancer Organization, Eindhoven, and VieCuri Medical Centre, Venlo; Pieter J. Westenend, Laboratory for Pathology, Dordrecht; Jan J. Jobsen, Medisch Spectrum Twente, Enschede; and Sabine Sieling, Netherlands Comprehensive Cancer Organization, Utrecht, Netherlands. mk.schmidt@nki.nl.
Abstract
PURPOSE: To determine prospectively overall and age-specific estimates of contralateral breast cancer (CBC) risk for young patients with breast cancer with or without BRCA1/2 mutations. PATIENTS AND METHODS: A cohort of 6,294 patients with invasive breast cancer diagnosed under 50 years of age and treated between 1970 and 2003 in 10 Dutch centers was tested for the most prevalent BRCA1/2 mutations. We report absolute risks and hazard ratios within the cohort from competing risk analyses. RESULTS: After a median follow-up of 12.5 years, 578 CBCs were observed in our study population. CBC risk for BRCA1 and BRCA2 mutation carriers was two to three times higher than for noncarriers (hazard ratios, 3.31 [95% CI, 2.41 to 4.55; P < .001] and 2.17 [95% CI,1.22 to 3.85; P = .01], respectively). Ten-year cumulative CBC risks were 21.1% (95% CI, 15.4 to 27.4) for BRCA1, 10.8% (95% CI, 4.7 to 19.6) for BRCA2 mutation carriers and 5.1% (95% CI, 4.5 to 5.7) for noncarriers. Age at diagnosis of the first breast cancer was a significant predictor of CBC risk in BRCA1/2 mutation carriers only; those diagnosed before age 41 years had a 10-year cumulative CBC risk of 23.9% (BRCA1: 25.5%; BRCA2: 17.2%) compared with 12.6% (BRCA1: 15.6%; BRCA2: 7.2%) for those 41 to 49 years of age (P = .02); our review of published studies showed ranges of 24% to 31% before age 40 years (BRCA1: 24% to 32%; BRCA2:17% to 29%) and 8% to 21% after 40 years (BRCA1: 11% to 52%; BRCA2: 7% to 18%), respectively. CONCLUSION: Age at first breast cancer is a strong risk factor for cumulative CBC risk in BRCA1/2 mutation carriers. Considering the available evidence, age-specific risk estimates should be included in counseling.
PURPOSE: To determine prospectively overall and age-specific estimates of contralateral breast cancer (CBC) risk for young patients with breast cancer with or without BRCA1/2 mutations. PATIENTS AND METHODS: A cohort of 6,294 patients with invasive breast cancer diagnosed under 50 years of age and treated between 1970 and 2003 in 10 Dutch centers was tested for the most prevalent BRCA1/2 mutations. We report absolute risks and hazard ratios within the cohort from competing risk analyses. RESULTS: After a median follow-up of 12.5 years, 578 CBCs were observed in our study population. CBC risk for BRCA1 and BRCA2 mutation carriers was two to three times higher than for noncarriers (hazard ratios, 3.31 [95% CI, 2.41 to 4.55; P < .001] and 2.17 [95% CI,1.22 to 3.85; P = .01], respectively). Ten-year cumulative CBC risks were 21.1% (95% CI, 15.4 to 27.4) for BRCA1, 10.8% (95% CI, 4.7 to 19.6) for BRCA2 mutation carriers and 5.1% (95% CI, 4.5 to 5.7) for noncarriers. Age at diagnosis of the first breast cancer was a significant predictor of CBC risk in BRCA1/2 mutation carriers only; those diagnosed before age 41 years had a 10-year cumulative CBC risk of 23.9% (BRCA1: 25.5%; BRCA2: 17.2%) compared with 12.6% (BRCA1: 15.6%; BRCA2: 7.2%) for those 41 to 49 years of age (P = .02); our review of published studies showed ranges of 24% to 31% before age 40 years (BRCA1: 24% to 32%; BRCA2:17% to 29%) and 8% to 21% after 40 years (BRCA1: 11% to 52%; BRCA2: 7% to 18%), respectively. CONCLUSION: Age at first breast cancer is a strong risk factor for cumulative CBC risk in BRCA1/2 mutation carriers. Considering the available evidence, age-specific risk estimates should be included in counseling.
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Authors: Hesham Elghazaly; Hope S Rugo; Hamdy A Azim; Sandra M Swain; Banu Arun; Matti Aapro; Edith A Perez; Benjamin O Anderson; Frederique Penault-Llorca; Pierfranco Conte; Nagi S El Saghir; Cheng-Har Yip; Marwan Ghosn; Philip Poortmans; Mohamed A Shehata; Armando E Giuliano; Jessica W T Leung; Valentina Guarneri; Joseph Gligorov; Bahadir M Gulluoglu; Hany Abdel Aziz; Mona Frolova; Mohamed Sabry; Charles M Balch; Roberto Orecchia; Heba M El-Zawahry; Sana Al-Sukhun; Khaled Abdel Karim; Alaa Kandil; Ruslan M Paltuev; Meteb Foheidi; Mohamed El-Shinawi; Manal ElMahdy; Omalkhair Abulkhair; Wentao Yang; Adel T Aref; Joaira Bakkach; Nermean Bahie Eldin; Hagar Elghazawy Journal: Cancers (Basel) Date: 2021-05-08 Impact factor: 6.639
Authors: Iris Kramer; Maartje J Hooning; Nasim Mavaddat; Michael Hauptmann; Renske Keeman; Ewout W Steyerberg; Daniele Giardiello; Antonis C Antoniou; Paul D P Pharoah; Sander Canisius; Zumuruda Abu-Ful; Irene L Andrulis; Hoda Anton-Culver; Kristan J Aronson; Annelie Augustinsson; Heiko Becher; Matthias W Beckmann; Sabine Behrens; Javier Benitez; Marina Bermisheva; Natalia V Bogdanova; Stig E Bojesen; Manjeet K Bolla; Bernardo Bonanni; Hiltrud Brauch; Michael Bremer; Sara Y Brucker; Barbara Burwinkel; Jose E Castelao; Tsun L Chan; Jenny Chang-Claude; Stephen J Chanock; Georgia Chenevix-Trench; Ji-Yeob Choi; Christine L Clarke; J Margriet Collée; Fergus J Couch; Angela Cox; Simon S Cross; Kamila Czene; Mary B Daly; Peter Devilee; Thilo Dörk; Isabel Dos-Santos-Silva; Alison M Dunning; Miriam Dwek; Diana M Eccles; D Gareth Evans; Peter A Fasching; Henrik Flyger; Manuela Gago-Dominguez; Montserrat García-Closas; José A García-Sáenz; Graham G Giles; David E Goldgar; Anna González-Neira; Christopher A Haiman; Niclas Håkansson; Ute Hamann; Mikael Hartman; Bernadette A M Heemskerk-Gerritsen; Antoinette Hollestelle; John L Hopper; Ming-Feng Hou; Anthony Howell; Hidemi Ito; Milena Jakimovska; Anna Jakubowska; Wolfgang Janni; Esther M John; Audrey Jung; Daehee Kang; C Marleen Kets; Elza Khusnutdinova; Yon-Dschun Ko; Vessela N Kristensen; Allison W Kurian; Ava Kwong; Diether Lambrechts; Loic Le Marchand; Jingmei Li; Annika Lindblom; Jan Lubiński; Arto Mannermaa; Mehdi Manoochehri; Sara Margolin; Keitaro Matsuo; Dimitrios Mavroudis; Alfons Meindl; Roger L Milne; Anna Marie Mulligan; Taru A Muranen; Susan L Neuhausen; Heli Nevanlinna; William G Newman; Andrew F Olshan; Janet E Olson; Håkan Olsson; Tjoung-Won Park-Simon; Julian Peto; Christos Petridis; Dijana Plaseska-Karanfilska; Nadege Presneau; Katri Pylkäs; Paolo Radice; Gad Rennert; Atocha Romero; Rebecca Roylance; Emmanouil Saloustros; Elinor J Sawyer; Rita K Schmutzler; Lukas Schwentner; Christopher Scott; Mee-Hoong See; Mitul Shah; Chen-Yang Shen; Xiao-Ou Shu; Sabine Siesling; Susan Slager; Christof Sohn; Melissa C Southey; John J Spinelli; Jennifer Stone; William J Tapper; Maria Tengström; Soo Hwang Teo; Mary Beth Terry; Rob A E M Tollenaar; Ian Tomlinson; Melissa A Troester; Celine M Vachon; Chantal van Ongeval; Elke M van Veen; Robert Winqvist; Alicja Wolk; Wei Zheng; Argyrios Ziogas; Douglas F Easton; Per Hall; Marjanka K Schmidt Journal: Am J Hum Genet Date: 2020-10-05 Impact factor: 11.025