Adiposity Change Over the Life Course and Mammographic Breast Density in Postmenopausal Women.
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ABSTRACT:
SUBMITTER: Han Y
PROVIDER: S-EPMC8210631 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundEarly life adiposity and changes in adiposity over the life course are associated with mammographic breast density among postmenopausal women. However, the underlying mechanisms are unknown; therefore, we comprehensively examined the associations of early life body mass index (BMI) and changes in BMI from ages 10, 18 to age at mammogram with growth factor, RANK pathway, and sex hormone gene expression in 372 postmenopausal women.MethodsWe estimated early life BMI at age 10 using the validated 9-level Stunkard pictogram. We calculated BMI at other ages (18, 30, and current age at mammogram) by dividing weight in kilograms at these ages with height in meters squared. Sequencing for gene expression was performed using the NanoString nCounter system. After adjusting for confounders, we estimated associations using multivariable linear regressions.ResultsA 10 kg/m2 increase in early life BMI at age 10 was associated with a 17.2% decrease in RANKL gene expression (95% confidence interval [CI] = -30.8, -0.9) but was not associated with changes in other markers. BMI changes from ages 10, 18 to age at mammogram were associated with an increase in BMP2 and decreases in RANK, RANKL, and TNFRSF13B gene expression but were not associated with gene expression of other markers. A 10 kg/m2 increase in early life BMI from age 10 to current age was associated with a 7.8% increase in BMP2 (95% CI = -1.4, 17.8), an 8.5% decrease in RANK (95% CI = -13.9, -2.8), a 10.4% decrease in RANKL (95% CI = -16.9, -3.3), and an 8.5% decrease in TNFRSF13B gene expression (95% CI = -13.8, -2.8).ConclusionThe results provide new insights into the biological mechanisms underlying the associations of adiposity changes from early life to adulthood and early life adiposity with mammographic breast density in postmenopausal women.
| S-EPMC9249983 | biostudies-literature
Project description:Mammographic breast density (MBD) is a risk factor for breast cancer, but its molecular basis is poorly understood. Growth factors stimulate cellular and epithelial proliferation and could influence MBD via these mechanisms. Studies investigating the associations of circulating growth factors with MBD have, however, yielded conflicting results especially in postmenopausal women. We, therefore, investigated the associations of plasma growth factor gene expression [insulin-like growth factor (IGF)-1, IGF-binding protein 3, FGF-1, FGF-12, TGFβ1 and bone morphogenetic protein (BMP)-2] with MBD in postmenopausal women. We used NanoString nCounter platform to quantify plasma growth factor gene expression and Volpara to evaluate volumetric MBD measures. We investigated the associations of growth factor gene expression with MBD using both multiple linear regression (fold change) and multinomial logistic regression models, adjusted for potential confounders. The mean age of the 368 women enrolled was 58 years (range, 50-64). In analyses using linear regression models, one unit increase in IGF-1 gene expression was associated with a 35% higher volumetric percent density (VPD, 1.35; 95% confidence interval (CI), 1.13-1.60; P = 0.001). There were suggestions that TGFβ1 gene expression was positively associated with VPD while BMP-2 gene expression was inversely associated with VPD, but these were not statistically significant. In analyses using multinomial logistic regression, TGFβ1 gene expression was 33% higher (OR = 1.33; 95% CI, 1.13-1.56; P = 0.0008) in women with extremely dense breasts than those with almost entirely fatty breasts. There were no associations between growth factor gene expression and dense volume or nondense volume. Our study provides insights into the associations of growth factors with MBD in postmenopausal women and requires confirmation in other study populations.Prevention relevanceMammographic breast density is a strong risk factor for breast cancer. Understanding its underlying biological mechanisms could have utility in breast cancer prevention.
| S-EPMC9167743 | biostudies-literature
Project description:Mammographic density (MD) is a strong risk factor for breast cancer, but the biological mechanism underlying this association is not clear. Current adult body mass index (BMI) is inversely associated with percent MD; however, few studies have included Hispanic women or evaluated associations with measures of body fatness earlier in life. ESMaestras was established in 2006, when 28,345 women ages ?35 responded to a detailed questionnaire that assessed possible disease risk factors, including body fatness in childhood, adolescence, and young adulthood. In 2007, 2084 ESMaestras participants underwent a clinical examination, which included measurements of weight, height, and sitting height and a mammogram. We measured percent MD using a computer-assisted method. The current analysis includes 972 premenopausal and 559 postmenopausal women. We used multivariable linear regression to evaluate associations between measures of body size and MD, independent of current BMI. Among pre- and postmenopausal women, we observed no significant associations between body fatness during childhood, adolescence, or young adulthood and percent MD. Among postmenopausal women, we observed a modest positive association between body fatness immediately before first pregnancy and between ages 25 and 35 after adjustment for current BMI, with differences of 4.9 and 3.6 % points, respectively, in percent MD between the heaviest and leanest women (p-trend = 0.02). There were no significant associations between height, sitting height, and percent MD among pre- or postmenopausal women in multivariable models adjusting for BMI. In general, we found no clear associations between measures of body size in early life, current sitting height, or current height, and percent MD, after adjusting for current BMI, in this population of Mexican women. Our observation of a positive association between early adult body fatness (i.e., before first pregnancy and ages 25-35) and percent MD among postmenopausal women is inconsistent with prior research and requires confirmation in other studies.
| S-EPMC3627398 | biostudies-literature
Project description:PURPOSE:Consumption of alcoholic beverages during adolescence and early adulthood has been consistently associated with higher breast cancer risk. The influence of alcohol consumption early in life on mammographic breast density, a marker of breast cancer risk, is inconclusive. This study examined associations of alcohol consumption across the life course with premenopausal mammographic density. METHODS:The study population included 1211 premenopausal women in the Nurses' Health Study II without cancer, who recalled their alcohol consumption at age 15 through enrollment in 1989 (baseline), and had mammograms available. Recent alcohol consumption was updated over follow-up. Percent and absolute measures of mammographic density were quantified on digitized film mammograms. Generalized linear regression was used to assess associations. RESULTS:There were no notable differences in any of the three density measures for alcohol consumption at any age (15-17, 18-22, 23-30, and 31-mammogram). Neither alcohol consumption before first pregnancy nor after first pregnancy was significantly associated with any of the three density measures. CONCLUSIONS:Moderate alcohol consumption during different age intervals during adolescence and early adulthood was not associated with mammographic density in premenopausal women.
| S-EPMC5792299 | biostudies-literature
Project description:Background A decrease in breast density due to tamoxifen preventive therapy might indicate greater benefit from the drug. It is not known whether mammographic density continues to decline after 1 year of therapy, or whether measures of breast density change are sufficiently stable for personalised recommendations. Methods Mammographic density was measured annually over up to 5 years in premenopausal women with no previous diagnosis of breast cancer but at increased risk of breast cancer attending a family-history clinic in Manchester, UK (baseline 2010-2013). Tamoxifen (20 mg/day) for prevention was prescribed for up to 5 years in one group; the other group did not receive tamoxifen and were matched by age. Fully automatic methods were used on mammograms over the 5-year follow-up: three area-based measures (NN-VAS, Stratus, Densitas) and one volumetric (Volpara). Additionally, percentage breast density at baseline and first follow-up mammograms was measured visually. The size of density declines at the first follow-up mammogram and thereafter was estimated using a linear mixed model adjusted for age and body mass index. The stability of density change at 1 year was assessed by evaluating mean squared error loss from predictions based on individual or mean density change at 1 year. Results Analysis used mammograms from 126 healthy premenopausal women before and as they received tamoxifen for prevention (median age 42 years) and 172 matched controls (median age 41 years), with median 3 years follow-up. There was a strong correlation between percentage density measures used on the same mammogram in both the tamoxifen and no tamoxifen groups (all correlation coeficients > 0.8). Tamoxifen reduced mean breast density in year 1 by approximately 17–25% of the inter-quartile range of four automated percentage density measures at baseline, and from year 2, it decreased further by approximately 2–7% per year. Predicting change at 2 years using individual change at 1 year was approximately 60–300% worse than using mean change at 1year. Conclusions All measures showed a consistent and large average tamoxifen-induced change in density over the first year, and a continued decline thereafter. However, these measures of density change at 1 year were not stable on an individual basis.
| S-EPMC7523310 | biostudies-literature
Project description:BackgroundThe Alberta Physical Activity and Breast Cancer Prevention (ALPHA) Trial examined the influence of aerobic exercise on biological factors that are associated with breast cancer risk. Mammographic density, a secondary outcome, is reported here.MethodsThe ALPHA Trial was a parallel group randomized controlled trial conducted between May 2003 and July 2007. Postmenopausal, sedentary women ages 50 to 74 years (n = 320) were evenly randomized to aerobic exercise (45 minutes, 5 days per week) or control (usual life-style) for 1 year. Dense fibroglandular tissue and nondense fatty tissue were measured from mammograms at baseline and 1 year using computer-assisted thresholding software for area measurements and a new technique that relies on the calibration of mammography units with a tissue-equivalent phantom for volumetric measurements.ResultsNondense volume decreased in the exercise group relative to the control group (difference between groups = -38.5 cm(3); 95% confidence interval, -61.6 to 15.4; P = 0.001). Changes in total body fat accounted for this decrease. Changes in dense area and dense volume, measures that have previously been associated with breast cancer risk, were not significantly different between the groups (P > or = 0.26).ConclusionsAchieving changes in mammographic measures may require more exercise or a study population with higher baseline levels of sex hormones or a wider range of mammographic density. The data from this study, however, suggest that the protective effect of exercise on breast cancer risk may operate through a mechanism other than mammographic density.
| S-EPMC2945907 | biostudies-literature
Project description:BackgroundBreast density, as estimated by mammography, is a strong risk factor for breast cancer in pre- and postmenopausal women, but the determinants of breast density have not yet been established. The aim of this study was to assess if urinary estrogens or gut microbiota alterations are associated with mammographic density in postmenopausal women.MethodsAmong 54 cancer-free, postmenopausal controls in the Breast and Colon Health study, we classified low- versus high-density women with Breast Imaging Reporting and Data System (BI-RADS, 5th edition) mammographic screening data, then assessed associations with urinary estrogens and estrogen metabolites (determined by liquid chromatography/tandem mass spectrometry), and fecal microbiota alpha and beta diversity (using Illumina sequencing of 16S rRNA amplicons).ResultsMultiple logistic regression revealed no significant association between breast density and fecal microbiota metrics (PD_tree P-value = 0.82; un-weighted and weighted UniFrac P = 0.92 and 0.83, respectively, both by MiRKAT). In contrast, total urinary estrogens (and all 15 estrogens/estrogen metabolites) were strongly and inversely associated with breast density (P = 0.01) after adjustment for age and body mass index.ConclusionMammographic density was not associated with the gut microbiota, but it was inversely associated with urinary estrogen levels.ImpactThe finding of an inverse association between urinary estrogens and breast density in cancer-free women adds to the growing breast cancer literature on understanding the relationship between endogenous estrogens and mammographic density.
| S-EPMC6505928 | biostudies-literature
Project description:Few studies have shown that the association between mammographic breast density and breast cancer persists for up to 10 years after the mammogram. We investigated associations of percent density, absolute dense, and nondense areas with breast cancer risk according to the time since the mammogram.This study included 1,028 incident breast cancer cases diagnosed within the Nurses' Health Study and 1,780 matched controls. Breast density was measured from digitized film images with computerized techniques. Information on breast cancer risk factors was obtained prospectively from the biennial questionnaires before the date of cancer diagnosis for cases and their matched controls. The data were analyzed with logistic regression.Breast cancer risk increased with increasing percent density and increasing absolute dense area and decreased with increasing nondense area. In multivariate analysis, the magnitude of the association between percent density and breast cancer was similar when the time since the mammogram was <2, 2 to <5, and 5 to <10 years [density ?50% vs.<10%: ORs, 3.12; 95% confidence interval (CI): 1.55-6.25, 5.35 (95% CI: 2.93-9.76), and 3.91 (95%CI: 2.22-6.88), respectively]. Similarly, the magnitude of association between quartiles of dense and nondense areas and breast cancer risk were similar across the time strata. We found no interactions between the time since the mammogram and breast density measures (Pinteraction > 0.05).Patterns of the associations between percent density, absolute dense, and nondense area with breast cancer risk persist for up to 10 years after the mammogram.A one-time density measure can be used for long-term breast cancer risk prediction.
| S-EPMC3681889 | biostudies-literature
Project description:BackgroundProspective studies have consistently found that postmenopausal breast cancer risk increases with circulating estrogens; however, findings from studies of estrogens and mammographic density (MD), an intermediate marker of breast cancer risk, have been inconsistent. We investigated the cross-sectional associations of urinary estrogens, and their 2-, 4-, and 16-hydroxylated metabolites with MD.MethodsPostmenopausal women without breast cancer (n = 194), ages 48 to 82 years, and reporting no current menopausal hormone therapy use were enrolled at a clinic in Western NY in 2005. Urinary estrogens and estrogen metabolites were measured using mass spectrometry. Percent MD and dense area (cm(2)) were measured using computer-assisted analyses of digitized films. Linear regression models were used to estimate associations of log-transformed estrogen measures with MD while adjusting for age, body mass index (BMI), parity, and past hormone therapy use.ResultsUrinary concentrations of most individual estrogens and metabolites were not associated with MD; however, across the interdecile range of the ratio of parent estrogens (estrone and estradiol) to their metabolites, MD increased by 6.8 percentage points (P = 0.02) and dense area increased by 10.3 cm(2) (P = 0.03). Across the interdecile ranges of the ratios of 2-, 4-, and 16-hydroxylation pathways to the parent estrogens, MD declined by 6.2 (P = 0.03), 6.4 (P = 0.04), and 5.7 (P = 0.05) percentage points, respectively. All associations remained apparent in models without adjustment for BMI.ConclusionIn this study of postmenopausal women, less extensive hydroxylation of parent estrogens was associated with higher MD.ImpactHydroxylation of estrogens may modulate postmenopausal breast cancer risk through a pathway involving MD.
| S-EPMC3436977 | biostudies-literature
Project description:BackgroundHigh mammographic breast density (MBD) is a strong risk factor for breast cancer development, but the biological mechanisms underlying MBD are unclear. Lipids play important roles in cell differentiation, and perturbations in lipid metabolism are implicated in cancer development. Nevertheless, no study has applied untargeted lipidomics to profile the lipidome of MBD. Through this study, our goal is to characterize the lipidome of MBD in premenopausal women.MethodsPremenopausal women were recruited during their annual screening mammogram at the Washington University School of Medicine in St. Louis, MO. Untargeted lipidomic profiling for 982 lipid species was performed at Metabolon (Durham, NC®), and volumetric measures of MBD (volumetric percent density (VPD), dense volume (DV), and non-dense volume (NDV)) was assessed using Volpara 1.5 (Volpara Health®). We performed multivariable linear regression models to investigate the associations of lipid species with MBD and calculated the covariate-adjusted least square mean of MBD by quartiles of lipid species. MBD measures were log10 transformed, and lipid species were standardized. Linear coefficients of MBD were back-transformed and considered significant if the Bonferroni corrected p-value was < 0.05.ResultsOf the 705 premenopausal women, 72% were non-Hispanic white, and 23% were non-Hispanic black. Mean age, and BMI were 46 years and 30 kg/m2, respectively. Fifty-six lipid species were significantly associated with VPD (52 inversely and 4 positively). The lipid species with positive associations were phosphatidylcholine (PC)(18:1/18:1), lysophosphatidylcholine (LPC)(18:1), lactosylceramide (LCER)(14:0), and phosphatidylinositol (PI)(18:1/18:1). VPD increased across quartiles of PI(18:1/18:1): (Q1 = 7.5%, Q2 = 7.7%, Q3 = 8.4%, Q4 = 9.4%, Bonferroni p-trend = 0.02). The lipid species that were inversely associated with VPD were mostly from the triacylglycerol (N = 43) and diacylglycerol (N = 7) sub-pathways. Lipid species explained some of the variation in VPD. The inclusion of lipid species increased the adjusted R2 from 0.45, for a model that includes known determinants of VPD, to 0.59.ConclusionsWe report novel lipid species that are associated with MBD in premenopausal women. Studies are needed to validate our results and the translational potential.
| S-EPMC10561435 | biostudies-literature