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Body fatness during childhood and adolescence and breast density in young women: a prospective analysis.

ABSTRACT: INTRODUCTION:Overweight and obesity in childhood and adolescence are associated with reduced breast cancer risk, independent of adult body mass index (BMI). These associations may be mediated through breast density. METHODS:We prospectively examined associations of early life body fatness with adult breast density measured by MRI in 182 women in the Dietary Intervention Study in Children (DISC) who were ages 25-29 at follow-up. Height, weight, and other factors were measured at baseline (ages 8-10) and annual clinic visits through adolescence. We used linear mixed-effects models to quantify associations of percent breast density and dense and non-dense breast volume at ages 25-29 with quartiles of age-specific youth body mass index (BMI) Z-scores, adjusting for clinic, treatment group, current adult BMI, and other well-established risk factors for breast cancer and predictors of breast density. RESULTS:We observed inverse associations between age-specific BMI Z-scores at all youth clinic visits and percent breast density, adjusting for current adult BMI and other covariates (all p values <0.01). Women whose baseline BMI Z-scores (at ages 8-10 years) were in the top quartile had significantly lower adult breast density, after adjusting for current adult BMI and other covariates [least squares mean (LSM): 23.4 %; 95 % confidence interval (CI): 18.0 %, 28.8 %] compared to those in the bottom quartile (LSM: 31.8 %; 95 % CI: 25.2 %, 38.4 %) (p trend <0.01). Significant inverse associations were also observed for absolute dense breast volume (all p values <0.01), whereas there were no clear associations with non-dense breast volume. CONCLUSIONS:These results support the hypothesis that body fatness during childhood and adolescence may play an important role in premenopausal breast density, independent of current BMI, and further suggest direct or indirect influences on absolute dense breast volume. CLINICAL TRIALS REGISTRATION NUMBER:NCT00458588 ; April 9, 2007.

SUBMITTER: Bertrand KA

PROVIDER: S-EPMC4502611 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Body fatness during childhood and adolescence and breast density in young women: a prospective analysis.

Bertrand Kimberly A KA Baer Heather J HJ Orav E John EJ Klifa Catherine C Shepherd John A JA Van Horn Linda L Snetselaar Linda L Stevens Victor J VJ Hylton Nola M NM Dorgan Joanne F JF

Breast cancer research : BCR 20150716

<h4>Introduction</h4>Overweight and obesity in childhood and adolescence are associated with reduced breast cancer risk, independent of adult body mass index (BMI). These associations may be mediated through breast density.<h4>Methods</h4>We prospectively examined associations of early life body fatness with adult breast density measured by MRI in 182 women in the Dietary Intervention Study in Children (DISC) who were ages 25-29 at follow-up. Height, weight, and other factors were measured at ba ...[more]

PMID: 26174168

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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:BackgroundThe treatment of Hodgkin's disease (HD; also called Hodgkin's lymphoma) in children and adolescents with radiotherapy and chemotherapy leads to high survival rates but has a number of late effects. The most serious one is the development of a secondary malignant tumor, usually in the field that was irradiated. In women, breast cancer can arise in this way.MethodData on the occurrence of secondary breast cancer (sBC) were collected from 590 women who were treated in five consecutive pediatric HD treatment studies in the years 1978-1995 and then re-evaluated in a late follow-up study after a median interval of 17.8 years (maximum, 33.7 years). Information was obtained from 1999 onward by written inquiry to the participants and their treating physicians. The cumulative incidence of sBC was calculated by the Gooley method.ResultsBy July 2012, sBC had been diagnosed in 26 of 590 female HD patients; the breast cancer was in the irradiated field in 25 of these 26 patients. Their age at the time of treatment for HD was 9.9 to 16.2 years (the pubertal phase), and sBC was discovered with a median latency of 20.7 years after HD treatment (shortest latency, 14.3 years) and at a median age of 35.3 years (youngest age, 26.8 years). The radiation dose to the supradiaphragmatic fields ranged from 20 to 45 Gy. The cumulative incidence for sBC 30 years after treatment for HD was 19% (95% confidence interval, 12% to 29%). For women aged 25 to 45 in this series, the frequency of breast cancer was 24 times as high as in the corresponding normal population.ConclusionWomen who were treated for HD in childhood or adolescence have an increased risk of developing breast cancer as young adults. The risk is associated with prior radiotherapy and with the age at which it was administered (the pubertal phase). Because of these findings, a structured breast cancer screening project for this high-risk group has been initiated in collaboration with the German Consortium for Hereditary Breast and Ovarian Cancer (Deutsches Konsortium für familiären Brust- und Eierstockkrebs).

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Body fatness during childhood and adolescence and breast density in young women: a prospective analysis.

Publications

Body fatness during childhood and adolescence and breast density in young women: a prospective analysis.

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