Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/7606
Mammographic density and breast cancer in women from high risk families
Ramón Y Cajal, Teresa | Chirivella, Isabel | Miranda, Josefa | Teule, Alexandre | Izquierdo, Ángel | Balmaña, Judith | Sánchez-Heras, Ana Beatriz | Llort, Gemma | Fisas, David | Lope, Virginia ISCIII | Hernández-Agudo, Elena | Juan-Fita, María José | Tena, Isabel | Robles, Luis | Guillén-Ponce, Carmen | Pérez-Segura, Pedro | Luque-Molina, Mari Sol | Hernando-Polo, Susana | Salinas, Mónica | Brunet, Joan | Salas-Trejo, Dolores | Barnadas, Agustí | Pollan-Santamaria, Marina ISCIII
Breast Cancer Res. 2015 Jul 11;17:93.
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.
Adult | Breast Density | Breast Neoplasms | Female | Genes, BRCA1 | Genes, BRCA2 | Genetic Predisposition to Disease | Hereditary Breast and Ovarian Cancer Syndrome | Heterozygote | Humans | Mammary Glands, Human | Mammography | Middle Aged | Mutation | Odds Ratio | Risk Factors | Family
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