PURPOSE: BRCA1-related breast cancers are more frequently estrogen receptor (ER) negative than are either BRCA2-related or nonhereditary breast cancers. The relationship between ER status and other clinical features of hereditary breast cancers has not been well studied. EXPERIMENTAL DESIGN: ER status, grade, and histological tumor type were evaluated in 1131 women with invasive breast cancer, ascertained at 10 centers in North America. There were 208 BRCA1 mutation carriers, 88 BRCA2 carriers, and 804 women without a known mutation. We stratified the patients by mutation status, grade, age, and histological type and calculated the percentage of ER-positive tumors within each stratum. RESULTS: BRCA1 mutation carriers were more likely to have ER-negative breast cancers than were women in other groups, after adjustment for age, grade, and histological subtype (P < 0.001). Only 3.9% of BRCA1-related breast cancers were ER-positive cancers occurring in women in their postmenopausal years. The direction and magnitude of the change in ER status with increasing age at diagnosis in BRCA1 carriers was significantly different from in BRCA2 carriers (P(intercept) = 0.0002, P(slope) = 0.04). Notably, changes in ER status with age at diagnosis for BRCA1 carriers and noncarriers were almost identical (P(slope) = 0.98). CONCLUSIONS: The strong relationship between the presence of a BRCA1 mutation and the ER-negative status of the breast cancers is neither a consequence of the young age at onset nor the high grade but is an intrinsic property of BRCA1-related cancers. The ER-negative status of these cancers may reflect the cell of origin of BRCA1-related cancers.
PURPOSE:BRCA1-related breast cancers are more frequently estrogen receptor (ER) negative than are either BRCA2-related or nonhereditary breast cancers. The relationship between ER status and other clinical features of hereditary breast cancers has not been well studied. EXPERIMENTAL DESIGN:ER status, grade, and histological tumor type were evaluated in 1131 women with invasive breast cancer, ascertained at 10 centers in North America. There were 208 BRCA1 mutation carriers, 88 BRCA2 carriers, and 804 women without a known mutation. We stratified the patients by mutation status, grade, age, and histological type and calculated the percentage of ER-positive tumors within each stratum. RESULTS:BRCA1 mutation carriers were more likely to have ER-negative breast cancers than were women in other groups, after adjustment for age, grade, and histological subtype (P < 0.001). Only 3.9% of BRCA1-related breast cancers were ER-positive cancers occurring in women in their postmenopausal years. The direction and magnitude of the change in ER status with increasing age at diagnosis in BRCA1 carriers was significantly different from in BRCA2 carriers (P(intercept) = 0.0002, P(slope) = 0.04). Notably, changes in ER status with age at diagnosis for BRCA1 carriers and noncarriers were almost identical (P(slope) = 0.98). CONCLUSIONS: The strong relationship between the presence of a BRCA1 mutation and the ER-negative status of the breast cancers is neither a consequence of the young age at onset nor the high grade but is an intrinsic property of BRCA1-related cancers. The ER-negative status of these cancers may reflect the cell of origin of BRCA1-related cancers.
Authors: Nasim Mavaddat; Daniel Barrowdale; Irene L Andrulis; Susan M Domchek; Diana Eccles; Heli Nevanlinna; Susan J Ramus; Amanda Spurdle; Mark Robson; Mark Sherman; Anna Marie Mulligan; Fergus J Couch; Christoph Engel; Lesley McGuffog; Sue Healey; Olga M Sinilnikova; Melissa C Southey; Mary Beth Terry; David Goldgar; Frances O'Malley; Esther M John; Ramunas Janavicius; Laima Tihomirova; Thomas V O Hansen; Finn C Nielsen; Ana Osorio; Alexandra Stavropoulou; Javier Benítez; Siranoush Manoukian; Bernard Peissel; Monica Barile; Sara Volorio; Barbara Pasini; Riccardo Dolcetti; Anna Laura Putignano; Laura Ottini; Paolo Radice; Ute Hamann; Muhammad U Rashid; Frans B Hogervorst; Mieke Kriege; Rob B van der Luijt; Susan Peock; Debra Frost; D Gareth Evans; Carole Brewer; Lisa Walker; Mark T Rogers; Lucy E Side; Catherine Houghton; JoEllen Weaver; Andrew K Godwin; Rita K Schmutzler; Barbara Wappenschmidt; Alfons Meindl; Karin Kast; Norbert Arnold; Dieter Niederacher; Christian Sutter; Helmut Deissler; Doroteha Gadzicki; Sabine Preisler-Adams; Raymonda Varon-Mateeva; Ines Schönbuchner; Heidrun Gevensleben; Dominique Stoppa-Lyonnet; Muriel Belotti; Laure Barjhoux; Claudine Isaacs; Beth N Peshkin; Trinidad Caldes; Miguel de la Hoya; Carmen Cañadas; Tuomas Heikkinen; Päivi Heikkilä; Kristiina Aittomäki; Ignacio Blanco; Conxi Lazaro; Joan Brunet; Bjarni A Agnarsson; Adalgeir Arason; Rosa B Barkardottir; Martine Dumont; Jacques Simard; Marco Montagna; Simona Agata; Emma D'Andrea; Max Yan; Stephen Fox; Timothy R Rebbeck; Wendy Rubinstein; Nadine Tung; Judy E Garber; Xianshu Wang; Zachary Fredericksen; Vernon S Pankratz; Noralane M Lindor; Csilla Szabo; Kenneth Offit; Rita Sakr; Mia M Gaudet; Christian F Singer; Muy-Kheng Tea; Christine Rappaport; Phuong L Mai; Mark H Greene; Anna Sokolenko; Evgeny Imyanitov; Amanda Ewart Toland; Leigha Senter; Kevin Sweet; Mads Thomassen; Anne-Marie Gerdes; Torben Kruse; Maria Caligo; Paolo Aretini; Johanna Rantala; Anna von Wachenfeld; Karin Henriksson; Linda Steele; Susan L Neuhausen; Robert Nussbaum; Mary Beattie; Kunle Odunsi; Lara Sucheston; Simon A Gayther; Kate Nathanson; Jenny Gross; Christine Walsh; Beth Karlan; Georgia Chenevix-Trench; Douglas F Easton; Antonis C Antoniou Journal: Cancer Epidemiol Biomarkers Prev Date: 2011-12-05 Impact factor: 4.254
Authors: Joyce Liu; Mihaela C Cristea; Paul Frankel; Susan L Neuhausen; Linda Steele; Verena Engelstaedter; Ursula Matulonis; Sharon Sand; Nadine Tung; Judy E Garber; Jeffrey N Weitzel Journal: Cancer Genet Date: 2012 Jan-Feb
Authors: Soley Bayraktar; Angelica M Gutierrez-Barrera; Diane Liu; Tunc Tasbas; Ugur Akar; Jennifer K Litton; E Lin; Constance T Albarracin; Funda Meric-Bernstam; Ana M Gonzalez-Angulo; Gabriel N Hortobagyi; Banu K Arun Journal: Breast Cancer Res Treat Date: 2011-08-10 Impact factor: 4.872
Authors: Robert M W Hofstra; Amanda B Spurdle; Diana Eccles; William D Foulkes; Niels de Wind; Nicoline Hoogerbrugge; Frans B L Hogervorst Journal: Hum Mutat Date: 2008-11 Impact factor: 4.878
Authors: P Shah; M Rosen; J Stopfer; J Siegfried; R Kaltman; B Mason; K Armstrong; K L Nathanson; M Schnall; S M Domchek Journal: Breast Cancer Res Treat Date: 2009-07-17 Impact factor: 4.872