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Adiposity, breast density, and breast cancer risk: epidemiological and biological considerations.

ABSTRACT: Excess total body fat and abdominal adipose tissue are recognized risk factors for metabolic diseases but also for some types of cancers, including breast cancer. Several biological mechanisms in connection with local and systemic effects of adiposity are believed to be implicated in breast cancer development, and may involve breast fat. Breast adipose tissue can be studied through mammography by looking at breast density features such as the nondense area mainly composed of fat, or the percent breast density, which is the proportion of fibroglandular tissue in relation to fat. The relation between adiposity, breast density features, and breast cancer is complex. Studies suggest a paradoxical association as adiposity and absolute nondense area correlate positively with each other, but in contrast to adiposity, absolute nondense area seems to be associated negatively with breast cancer risk. As breast density is one of the strongest risk factors for breast cancer, it is therefore critical to understand how these factors interrelate. In this review, we discuss these relations by first presenting how adiposity measurements and breast density features are linked to breast cancer risk. Then, we used a systematic approach to capture the literature to review the relation between adiposity and breast density features. Finally, the role of adipose tissue in carcinogenesis is discussed briefly from a biological perspective.

SUBMITTER: Soguel L

PROVIDER: S-EPMC5627530 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Adiposity, breast density, and breast cancer risk: epidemiological and biological considerations.

Soguel Ludivine L Durocher Francine F Tchernof André A Diorio Caroline C

European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) 20171101 6

Excess total body fat and abdominal adipose tissue are recognized risk factors for metabolic diseases but also for some types of cancers, including breast cancer. Several biological mechanisms in connection with local and systemic effects of adiposity are believed to be implicated in breast cancer development, and may involve breast fat. Breast adipose tissue can be studied through mammography by looking at breast density features such as the nondense area mainly composed of fat, or the percent ...[more]

PMID: 27571214

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Project description:BackgroundChildhood adiposity is inversely associated with young adult percent dense breast volume (%DBV) and absolute dense breast volume (ADBV), which could contribute to its protective effect for breast cancer later in life. The objective of this study was to identify metabolites in childhood serum that may mediate the inverse association between childhood adiposity and young adult breast density.MethodsLongitudinal data from 182 female participants in the Dietary Intervention Study in Children (DISC) and the DISC 2006 (DISC06) Follow-Up Study were analyzed. Childhood adiposity was assessed by anthropometry at the DISC visit with serum available that occurred closest to menarche and expressed as a body mass index (BMI) z-score. Serum metabolites were measured by untargeted metabolomics using ultra-high-performance liquid chromatography-tandem mass spectrometry. %DBV and ADBV were measured by magnetic resonance imaging at the DISC06 visit when participants were 25-29 years old. Robust mixed effects linear regression was used to identify serum metabolites associated with childhood BMI z-scores and breast density, and the R package mediation was used to quantify mediation.ResultsOf the 115 metabolites associated with BMI z-scores (FDR < 0.20), 4 were significantly associated with %DBV and 6 with ADBV before, though not after, adjustment for multiple comparisons. Mediation analysis identified 2 unnamed metabolites, X-16576 and X-24588, as potential mediators of the inverse association between childhood adiposity and dense breast volume. X-16576 mediated 14% (95% confidence interval (CI) = 0.002, 0.46; P = 0.04) of the association of childhood adiposity with %DBV and 11% (95% CI = 0.01, 0.26; P = 0.02) of its association with ADBV. X-24588 also mediated 7% (95% CI = 0.001, 0.18; P = 0.05) of the association of childhood adiposity with ADBV. None of the other metabolites examined contributed to mediation of the childhood adiposity-%DBV association, though there was some support for contributions of lysine, valine and 7-methylguanine to mediation of the inverse association of childhood adiposity with ADBV.ConclusionsAdditional large longitudinal studies are needed to identify metabolites and other biomarkers that mediate the inverse association of childhood adiposity with breast density and possibly breast cancer risk.

Project description:BackgroundDespite widespread implementation of mammographic breast density (MBD) notification laws, the impact of these laws on knowledge of MBD and knowledge of breast cancer risk is limited by the lack of tools to promote informed decision-making in practice.ObjectiveTo develop and evaluate whether brief, personalized informational videos following a normal mammogram in addition to a legislatively required letter about MBD result can improve knowledge of MBD and breast cancer risk compared to standard care (i.e., legislatively required letter about MBD included with the mammogram result).Design/participantsProspective randomized controlled trial of English-speaking women, age 40-74 years, without prior history of breast cancer, receiving a screening mammogram with a normal or benign finding (intervention group n = 235, control group n = 224).Interventionbrief (3-5 min) video, personalized to a woman's MBD result and breast cancer risk.Main measuresPrimary outcomes were a woman's knowledge of her MBD and risk of breast cancer. Secondary outcomes included whether a woman reported that she discussed the results of her mammogram with her primary care provider (PCP).Key resultsRelative to women in the control arm, women in the intervention arm had greater improvement in their knowledge of both their personal MBD (intervention pre/post 39.2%/ 77.5%; control pre/post 36.2%/ 37.5%; odds ratio (OR) 5.34 for change for intervention vs. control, 95% confidence interval (CI) 3.87-7.36; p < 0.001) and risk of breast cancer (intervention pre/post: 66.8%/74.0%; control pre/post 67.9%/ 65.2%; OR 1.42, 95% confidence interval (CI) 1.09-1.84; p = 0.01). Women in the intervention group were more likely than those in the control group to report discussing the results of their mammogram with their PCP (p = 0.05).ConclusionsBrief, personalized videos following mammography can improve knowledge of MBD and personal risk of breast cancer compared to a legislatively mandated informational letter. Trial Registration Clinicaltrials.gov (NCT02986360).

Dataset Information

Adiposity, breast density, and breast cancer risk: epidemiological and biological considerations.

Publications

Adiposity, breast density, and breast cancer risk: epidemiological and biological considerations.

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