Year: 2015
Type: article
Study design: Observational Study
Abstract: INTRODUCTION: Mammographic density (MD) is one of the strongest determinants of sporadic breast cancer (BC). In this study, we compared MD in BRCA1/2 mutation carriers and non-carriers from BRCA1/2 mutation-positive families and investigated the association between MD and BC among BRCA1/2 mutation carriers per type of mutation and tumor subtype. METHODS: The study was carried out in 1039 female members of BRCA1 and BRCA2 mutation-positive families followed at 16 Spanish Genetic Counseling Units. Participants' density was scored retrospectively from available mammograms by a single blinded radiologist using a 5-category scale (<10 %, 10-25 %, 25-50 %, 50-75 %, >75 %). In BC cases, we selected mammograms taken prior to diagnosis or from the contralateral breast, whereas, in non-cases, the last screening mammogram was evaluated. MD distribution in carriers and non-carriers was compared using ordinal logistic models, and the association between MD and BC in BRCA1/2 mutation carriers was studied using logistic regression. Huber-White robust estimators of variance were used to take into account correlations between family members. A similar multinomial model was used to explore this association by BC subtype. RESULTS: We identified and scored mammograms from 341 BRCA1, 350 BRCA2 mutation carriers and 229 non-carriers. Compared to non-carriers, MD was significantly lower among BRCA2 mutation carriers (odds ratio (OR) =0.71; P-value=0.04), but not among BRCA1 carriers (OR=0.84; P-value=0.33). MD was associated with subsequent development BC (OR per category of MD=1.45; 95 % confidence interval=1.18-1.78, P-value<0.001), with no significant differences between BRCA1 and BRCA2 mutation carriers (P-value=0.48). Finally, no statistically significant differences were observed in the association of MD with specific BC subtypes. CONCLUSIONS: Our study, the largest to date on this issue, confirms that MD is an independent risk factor for all BC subtypes in either BRCA1 and BRCA2 mutation carriers, and should be considered a phenotype risk marker in this context.
Source: Breast Cancer Research
Authors: Teresa Ramón y Cajal, Isabel Chirivella, Josefa Miranda, Alexandre Teule, Ángel Izquierdo, Judith Balmaña, Ana Beatriz Sánchez-Heras, Gemma Llort, David Fisas, Virginia Lope, Elena Hernández-Agudo, María José Juan-Fita, Isabel Tena, Luis Robles, Carmen Guillén-Ponce, Pedro Pérez-Segura, Mari Sol Luque-Molina, Susana Hernando-Polo, Mónica Salinas, Joan Brunet, María Dolores Salas-Trejo, Agustí Barnadas, Marina Pollán
Institutions: Hospital de Sant Pau, Hospital Clínico Universitario de Valencia, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, Institut d'Investigació Biomédica de Bellvitge, Institut Català d'Oncologia, Institut d'Investigació Biomèdica de Girona, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institute of Oncology, Hospital General Universitario de Elche, Consorci Sanitari de Terrassa, Corporació Sanitària Parc Taulí, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Spanish National Cancer Research Centre, Fundación Instituto Valenciano de Oncología, Consorcio Hospitalario Provincial de Castellón, Fundación Hospital Provincial de Castellón, Hospital Universitario 12 De Octubre, Instituto Ramón y Cajal de Investigación Sanitaria, Hospital Universitario Ramón y Cajal, Hospital Clínico San Carlos, Hospital General Universitario Gregorio Marañón, Hospital Universitario Fundación Alcorcón, Universitat de Girona
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,190
OpenAlex ID: W2139100340