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Mammographic breast density and subsequent risk of breast cancer in postmenopausal women according to the time since the mammogram.

ABSTRACT: 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.

SUBMITTER: Yaghjyan L

PROVIDER: S-EPMC3681889 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Mammographic breast density and subsequent risk of breast cancer in postmenopausal women according to the time since the mammogram.

Yaghjyan Lusine L Colditz Graham A GA Rosner Bernard B Tamimi Rulla M RM

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20130419 6

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 23603205

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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.

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.

Dataset Information

Mammographic breast density and subsequent risk of breast cancer in postmenopausal women according to the time since the mammogram.

Publications

Mammographic breast density and subsequent risk of breast cancer in postmenopausal women according to the time since the mammogram.

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