BACKGROUND: Women with BRCA1 mutations develop breast cancer with similar pathologic features to sporadic triple negative (TN) breast cancer, a subtype associated with early disease relapse and poor outcome. The clinical outcome of women with and without BRCA1 mutations who had TN breast cancer treated with conventional chemotherapy were compared. METHODS: Women with stage I to III TN breast cancer who had BRCA1 testing within 36 months of diagnosis and received alkylating chemotherapy were identified from clinical databases and a Specialized Program of Research Excellence (SPORE) specimen bank. BRCA2 mutation carriers were excluded, resulting in a study cohort of 46 BRCA1 carriers and 71 noncarriers. Sites of metastasis, relapse rates, and survival were compared among carriers and noncarriers. The median follow-up was 75 months. RESULTS: BRCA1 carriers were younger at diagnosis (P < .001) and had smaller tumors (P = .03) than noncarriers. Freedom from distant metastasis at 5 years was 76% for carriers and 70% for noncarriers (hazard ratio [HR] 0.79, P = .5). Sites of distant recurrence did not differ significantly (P = .15), although BRCA1 carriers had a propensity for brain relapse (58% vs 24%, P = .06). Overall survival at 5 years was 82% for carriers and 74% for noncarriers (HR 0.64, P = .25). Adjusting for age and stage, BRCA1 mutation status was not an independent predictor of survival (HR 0.73, P = .48). CONCLUSIONS: BRCA1 mutation carriers with TN disease had similar survival rates to noncarriers when treated with alkylating chemotherapy. Women with BRCA1-related breast cancer may benefit from novel therapies that target DNA repair, and further study is needed to identify sporadic TN breast cancers with a BRCA-deficient phenotype.
BACKGROUND:Women with BRCA1 mutations develop breast cancer with similar pathologic features to sporadic triple negative (TN) breast cancer, a subtype associated with early disease relapse and poor outcome. The clinical outcome of women with and without BRCA1 mutations who had TN breast cancer treated with conventional chemotherapy were compared. METHODS:Women with stage I to III TN breast cancer who had BRCA1 testing within 36 months of diagnosis and received alkylating chemotherapy were identified from clinical databases and a Specialized Program of Research Excellence (SPORE) specimen bank. BRCA2 mutation carriers were excluded, resulting in a study cohort of 46 BRCA1 carriers and 71 noncarriers. Sites of metastasis, relapse rates, and survival were compared among carriers and noncarriers. The median follow-up was 75 months. RESULTS:BRCA1 carriers were younger at diagnosis (P < .001) and had smaller tumors (P = .03) than noncarriers. Freedom from distant metastasis at 5 years was 76% for carriers and 70% for noncarriers (hazard ratio [HR] 0.79, P = .5). Sites of distant recurrence did not differ significantly (P = .15), although BRCA1 carriers had a propensity for brain relapse (58% vs 24%, P = .06). Overall survival at 5 years was 82% for carriers and 74% for noncarriers (HR 0.64, P = .25). Adjusting for age and stage, BRCA1 mutation status was not an independent predictor of survival (HR 0.73, P = .48). CONCLUSIONS:BRCA1 mutation carriers with TN disease had similar survival rates to noncarriers when treated with alkylating chemotherapy. Women with BRCA1-related breast cancer may benefit from novel therapies that target DNA repair, and further study is needed to identify sporadic TN breast cancers with a BRCA-deficient phenotype.
Authors: C T M Brekelmans; C Seynaeve; M Menke-Pluymers; H T Brüggenwirth; M M A Tilanus-Linthorst; C C M Bartels; M Kriege; A N van Geel; C M G Crepin; J C Blom; H Meijers-Heijboer; J G M Klijn Journal: Ann Oncol Date: 2005-12-01 Impact factor: 32.976
Authors: M Robson; T Gilewski; B Haas; D Levin; P Borgen; P Rajan; Y Hirschaut; P Pressman; P P Rosen; M L Lesser; L Norton; K Offit Journal: J Clin Oncol Date: 1998-05 Impact factor: 44.544
Authors: T Sørlie; C M Perou; R Tibshirani; T Aas; S Geisler; H Johnsen; T Hastie; M B Eisen; M van de Rijn; S S Jeffrey; T Thorsen; H Quist; J C Matese; P O Brown; D Botstein; P E Lønning; A L Børresen-Dale Journal: Proc Natl Acad Sci U S A Date: 2001-09-11 Impact factor: 11.205
Authors: Sunil R Lakhani; Marc J Van De Vijver; Jocelyne Jacquemier; Thomas J Anderson; Peter P Osin; Lesley McGuffog; Douglas F Easton Journal: J Clin Oncol Date: 2002-05-01 Impact factor: 44.544
Authors: Torsten O Nielsen; Forrest D Hsu; Kristin Jensen; Maggie Cheang; Gamze Karaca; Zhiyuan Hu; Tina Hernandez-Boussard; Chad Livasy; Dave Cowan; Lynn Dressler; Lars A Akslen; Joseph Ragaz; Allen M Gown; C Blake Gilks; Matt van de Rijn; Charles M Perou Journal: Clin Cancer Res Date: 2004-08-15 Impact factor: 12.531
Authors: Mark E Robson; Pierre O Chappuis; Jaya Satagopan; Nora Wong; Jeff Boyd; John R Goffin; Clifford Hudis; David Roberge; Larry Norton; Louis R Bégin; Kenneth Offit; William D Foulkes Journal: Breast Cancer Res Date: 2003-10-24 Impact factor: 6.466
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: Juliana Carvalho Santos; Marcelo Lima Ribeiro; Luis Otávio Sarian; Manoela Marques Ortega; Sophie Françoise Derchain Journal: Am J Cancer Res Date: 2016-10-01 Impact factor: 6.166
Authors: Allison W Kurian; Diego F Munoz; Peter Rust; Elizabeth A Schackmann; Michael Smith; Lauren Clarke; Meredith A Mills; Sylvia K Plevritis Journal: J Clin Oncol Date: 2012-01-09 Impact factor: 44.544
Authors: Nancy U Lin; Laleh Amiri-Kordestani; Diane Palmieri; David J Liewehr; Patricia S Steeg Journal: Clin Cancer Res Date: 2013-12-01 Impact factor: 12.531
Authors: Nicole M Davis; Melissa Sokolosky; Kristin Stadelman; Steve L Abrams; Massimo Libra; Saverio Candido; Ferdinando Nicoletti; Jerry Polesel; Roberta Maestro; Antonino D'Assoro; Lyudmyla Drobot; Dariusz Rakus; Agnieszka Gizak; Piotr Laidler; Joanna Dulińska-Litewka; Joerg Basecke; Sanja Mijatovic; Danijela Maksimovic-Ivanic; Giuseppe Montalto; Melchiorre Cervello; Timothy L Fitzgerald; Zoya Demidenko; Alberto M Martelli; Lucio Cocco; Linda S Steelman; James A McCubrey Journal: Oncotarget Date: 2014-07-15
Authors: Ahmed M Elnour; Abozer Y Elderdery; Jeremy Mills; Babiker A Mohammed; Daw Elbietabdelaal; Abdelraheem Osman Mohamed; Kamal Eldin H Elhassan; Abdel Hady A; Abdel Wahab; Alan Cooper Journal: Int J Health Sci (Qassim) Date: 2012-01