Association of the Interaction Between Mammographic Breast Density, Body Mass Index, and Menopausal Status With Breast Cancer Risk Among Korean Women.
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ABSTRACT:
SUBMITTER: Tran TXM
PROVIDER: S-EPMC8703253 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundObesity and elevated breast density are common risk factors for breast cancer, and their effects may vary by estrogen receptor (ER) subtype. However, their joint effects on ER subtype-specific risk are unknown. Understanding this relationship could enhance risk stratification for screening and prevention. Thus, we assessed the association between breast density and ER subtype according to body mass index (BMI) and menopausal status.MethodsWe conducted a case-control study nested within two mammography screening cohorts, the Mayo Mammography Health Study and the San Francisco Bay Area Breast Cancer SPORE/San Francisco Mammography Registry. Our pooled analysis contained 1538 ER-positive and 285 ER-negative invasive breast cancer cases and 4720 controls matched on age, menopausal status at time of mammogram, and year of mammogram. Percent density was measured on digitized film mammograms using computer-assisted techniques. We used polytomous logistic regression to evaluate the association between percent density and ER subtype by BMI subgroup (normal/underweight, < 25 kg/m2 versus overweight/obese, ≥ 25 kg/m2). We used Wald chi-squared tests to assess for interactions between percent density and BMI. Our analysis was stratified by menopausal status and hormone therapy usage at the time of index mammogram.ResultsPercent density was associated with increased risk of overall breast cancer regardless of menopausal status or BMI. However, when analyzing breast cancer across ER subtype, we found a statistically significant (p = 0.008) interaction between percent density and BMI in premenopausal women only. Specifically, elevated percent density was associated with a higher risk of ER-negative than ER-positive cancer in overweight/obese premenopausal women [OR per standard deviation increment 2.17 (95% CI 1.50-3.16) vs 1.33 (95% CI 1.11-1.61) respectively, Pheterogeneity = 0.01]. In postmenopausal women, elevated percent density was associated with similar risk of ER-positive and ER-negative cancers, and no substantive differences were seen after accounting for BMI or hormone therapy usage.ConclusionsThe combination of overweight/obesity and elevated breast density in premenopausal women is associated with a higher risk of ER-negative compared with ER-positive cancer. Eighteen percent of premenopausal women in the USA have elevated BMI and breast density and may benefit from lifestyle modifications involving weight loss and exercise.
| S-EPMC6448282 | biostudies-literature
Project description:BackgroundOverweight/obesity and dense breasts are strong breast cancer risk factors whose prevalences vary by race/ethnicity. The breast cancer population attributable risk proportions (PARP) explained by these factors across racial/ethnic groups are unknown.MethodsWe analyzed data collected from 3,786,802 mammography examinations (1,071,653 women) in the Breast Cancer Surveillance Consortium, associated with 21,253 invasive breast cancers during a median of 5.2 years follow-up. HRs for body mass index (BMI) and breast density, adjusted for age and registry were estimated using separate Cox regression models by race/ethnicity (White, Black, Hispanic, Asian) and menopausal status. HRs were combined with observed risk-factor proportions to calculate PARPs for shifting overweight/obese to normal BMI and shifting heterogeneously/extremely dense to scattered fibroglandular densities.ResultsThe prevalences and HRs for overweight/obesity and heterogeneously/extremely dense breasts varied across races/ethnicities and menopausal status. BMI PARPs were larger for postmenopausal versus premenopausal women (12.0%-28.3% vs. 1.0%-9.9%) and nearly double among postmenopausal Black women (28.3%) than other races/ethnicities (12.0%-15.4%). Breast density PARPs were larger for premenopausal versus postmenopausal women (23.9%-35.0% vs. 13.0%-16.7%) and lower among premenopausal Black women (23.9%) than other races/ethnicities (30.4%-35.0%). Postmenopausal density PARPs were similar across races/ethnicities (13.0%-16.7%).ConclusionsOverweight/obesity and dense breasts account for large proportions of breast cancers in White, Black, Hispanic, and Asian women despite large differences in risk-factor distributions.ImpactRisk prediction models should consider how race/ethnicity interacts with BMI and breast density. Efforts to reduce BMI could have a large impact on breast cancer risk reduction, particularly among postmenopausal Black women.
| S-EPMC7541499 | biostudies-literature
Project description:BackgroundThyroxine (T4) has been positively associated with tumor cell proliferation, while the effect of triiodothyronine (T3) on cell proliferation has not been well-established because it differs according to the type of cell line used. In Mexico, it has been reported that 14.5% of adult women have some type of thyroid dysfunction and abnormalities in thyroid function tests have been observed in a variety of non-thyroidal illnesses, including breast cancer (BC). These abnormalities might change with body mass index (BMI) because thyroid hormones are involved in the regulation of various metabolic pathways and probably by menopausal status because obesity has been negatively associated with BC in premenopausal women and has been positively associated with BC in postmenopausal women.MethodsTo assess the association between serum thyroid hormone concentration (T4 and T3) and BC and the influence of obesity as an effect modifier of this relationship in premenopausal and postmenopausal women, we measured serum thyroid hormone and thyroid antibody levels in 682 patients with incident breast cancer (cases) and 731 controls, who participated in a population-based case-control study performed from 2004 to 2007 in three states of Mexico. We tested the association of total T4 (TT4) and total T3 (TT3) stratifying by menopausal status and body mass index (BMI), and adjusted for other health and demographic risk factors using logistic regressions models.ResultsHigher serum total T4 (TT4) concentrations were associated with BC in both premenopausal (odds ratio (OR) per standard deviation?=?5.98, 95% CI 3.01-11.90) and postmenopausal women (OR per standard deviation?=?2.81, 95% CI 2.17-3.65). In premenopausal women, the effect of TT4 decreased as BMI increased while the opposite was observed in postmenopausal women. The significance of the effect modification was marginal (p?=?0.059) in postmenopausal women and was not significant in premenopausal women (p?=?0.22). Lower TT3 concentrations were associated with BC in both premenopausal and postmenopausal women and no effect modification was observed.ConclusionsThere is a strong association between BC and serum concentrations of TT3 and TT4; this needs to be further investigated to understand why it happens and how important it is to consider these alterations in treatment.
| S-EPMC6085630 | biostudies-literature
Project description:We examined the associations of mammographic breast density with breast cancer risk by tumor aggressiveness and by menopausal status and current postmenopausal hormone therapy.This study included 2596 invasive breast cancer cases and 4059 controls selected from participants of four nested case-control studies within four established cohorts: the Mayo Mammography Health Study, the Nurses' Health Study, Nurses' Health Study II, and San Francisco Mammography Registry. Percent breast density (PD), absolute dense (DA), and non-dense areas (NDA) were assessed from digitized film-screen mammograms using a computer-assisted threshold technique and standardized across studies. We used polytomous logistic regression to quantify the associations of breast density with breast cancer risk by tumor aggressiveness (defined as presence of at least two of the following tumor characteristics: size ?2 cm, grade 2/3, ER-negative status, or positive nodes), stratified by menopausal status and current hormone therapy.Overall, the positive association of PD and borderline inverse association of NDA with breast cancer risk was stronger in aggressive vs. non-aggressive tumors (?51 vs. 11-25% OR 2.50, 95% CI 1.94-3.22 vs. OR 2.03, 95% CI 1.70-2.43, p-heterogeneity = 0.03; NDA 4th vs. 2nd quartile OR 0.54, 95% CI 0.41-0.70 vs. OR 0.71, 95% CI 0.59-0.85, p-heterogeneity = 0.07). However, there were no differences in the association of DA with breast cancer by aggressive status. In the stratified analysis, there was also evidence of a stronger association of PD and NDA with aggressive tumors among postmenopausal women and, in particular, current estrogen+progesterone users (?51 vs. 11-25% OR 3.24, 95% CI 1.75-6.00 vs. OR 1.93, 95% CI 1.25-2.98, p-heterogeneity = 0.01; NDA 4th vs. 2nd quartile OR 0.43, 95% CI 0.21-0.85 vs. OR 0.56, 95% CI 0.35-0.89, p-heterogeneity = 0.01), even though the interaction was not significant.Our findings suggest that associations of mammographic density with breast cancer risk differ by tumor aggressiveness. While there was no strong evidence that these associations differed by menopausal status or hormone therapy, they did appear more prominent among current estrogen+progesterone users.
| S-EPMC5773252 | biostudies-literature
Project description:Breast adiposity is correlated with body mass index, menopausal status and mammary density. We here wish to establish how these factors influence the cross-talk between breast adipocytes and normal or malignant breast cells. Adipocyte-derived stem cells (ASCs) were obtained from healthy women and classified into six distinct groups based on body mass index, menopausal status and mammary density. The ASCs were induced to differentiate, and the influence of their conditioned media (ACM) was determined. Unexpectedly, there were no detectable differences in adipogenic differentiation and secretion between the six ASC groups, while their corresponding ACMs had no detectable influence on normal breast cells. In clear contrast, all ACMs profoundly influenced the proliferation, migration and invasiveness of malignant breast cells and increased the number of lipid droplets in their cytoplasm via increased expression of the fatty acid receptor CD36, thereby increasing fatty acid uptake. Importantly, inhibition of CD36 reduced lipid droplet accumulation and attenuated the migration and invasion of the breast cancer cells. These findings suggest that breast-associated adipocytes potentiate the invasiveness of breast cancer cells which, at least in part, is mediated by metabolic reprogramming via CD36-mediated fatty acid uptake.
| S-EPMC6966437 | biostudies-literature
Project description:BACKGROUND:Understanding how changes in body mass index (BMI) relate to changes in mammographic density is necessary to evaluate adjustment for BMI gain/loss in studies of change in density and breast cancer risk. Increase in BMI has been associated with a decrease in percent density, but the effect on change in absolute dense area or volume is unclear. METHODS:We examined the association between change in BMI and change in volumetric breast density among 24,556 women in the San Francisco Mammography Registry from 2007 to 2013. Height and weight were self-reported at the time of mammography. Breast density was assessed using single x-ray absorptiometry measurements. Cross-sectional and longitudinal associations between BMI and dense volume (DV), non-dense volume (NDV), and percent dense volume (PDV) were assessed using multivariable linear regression models, adjusted for demographics, risk factors, and reproductive history. RESULTS:In cross-sectional analysis, BMI was positively associated with DV [?, 2.95 cm(3); 95% confidence interval (CI), 2.69-3.21] and inversely associated with PDV (?, -2.03%; 95% CI, -2.09, -1.98). In contrast, increasing BMI was longitudinally associated with a decrease in both DV (?, -1.01 cm(3); 95% CI, -1.59, -0.42) and PDV (?, -1.17%; 95% CI, -1.31, -1.04). These findings were consistent for both pre- and postmenopausal women. CONCLUSION:Our findings support an inverse association between change in BMI and change in PDV. The association between increasing BMI and decreasing DV requires confirmation. IMPACT:Longitudinal studies of PDV and breast cancer risk, or those using PDV as an indicator of breast cancer risk, should evaluate adjustment for change in BMI.
| S-EPMC4633314 | biostudies-literature
Project description:BACKGROUND:Mammographic breast density, adjusted for age and body mass index, and a polygenic risk score (PRS), comprised of common genetic variation, are both strong risk factors for breast cancer and increase discrimination of risk models. Understanding their joint contribution will be important to more accurately predict risk. METHODS:Using 3628 breast cancer cases and 5126 controls of European ancestry from eight case-control studies, we evaluated joint associations of a 77-single nucleotide polymorphism (SNP) PRS and quantitative mammographic density measures with breast cancer. Mammographic percent density and absolute dense area were evaluated using thresholding software and examined as residuals after adjusting for age, 1/BMI, and study. PRS and adjusted density phenotypes were modeled both continuously (per 1 standard deviation, SD) and categorically. We fit logistic regression models and tested the null hypothesis of multiplicative joint associations for PRS and adjusted density measures using likelihood ratio and global and tail-based goodness of fit tests within the subset of six cohort or population-based studies. RESULTS:Adjusted percent density (odds ratio (OR)?=?1.45 per SD, 95% CI 1.38-1.52), adjusted absolute dense area (OR?=?1.34 per SD, 95% CI 1.28-1.41), and the 77-SNP PRS (OR?=?1.52 per SD, 95% CI 1.45-1.59) were associated with breast cancer risk. There was no evidence of interaction of the PRS with adjusted percent density or dense area on risk of breast cancer by either the likelihood ratio (P?>?0.21) or goodness of fit tests (P?>?0.09), whether assessed continuously or categorically. The joint association (OR) was 2.60 in the highest categories of adjusted PD and PRS and 0.34 in the lowest categories, relative to women in the second density quartile and middle PRS quintile. CONCLUSIONS:The combined associations of the 77-SNP PRS and adjusted density measures are generally well described by multiplicative models, and both risk factors provide independent information on breast cancer risk.
| S-EPMC6532188 | biostudies-literature
Project description:In analyses combining estrogen with or without progestin, some observational studies describe minimal breast cancer risk in obese and black women. Therefore, we examined these suggested interactions in the two Women's Health Initiative (WHI) randomized hormone therapy trials. The estrogen plus progestin trial entered 16 608 postmenopausal women with a uterus, while the estrogen trial entered 10 736 postmenopausal women with prior hysterectomy. Hazard ratios (HRs), 95% confidence intervals (CIs), and P values from log-rank x(2) statistics were estimated from Cox proportional hazards models with subgroup analyses based on tests of interaction. All statistical tests were two-sided. Estrogen plus progestin statistically significantly increased breast cancer incidence (HR = 1.28, 95% CI = 1.11 to 1.48, P < .001), with hazard ratios greater than 1 in all body mass index (BMI) subgroups (P interaction = .58) and hazard ratios greater than 1 in black and white women (P interaction = .96). In contrast, estrogen alone statistically significantly decreased breast cancer incidence (HR = 0.79, 95% CI = 0.65 to 0.90, P = .02), with hazard ratios lower than 1 in all BMI subgroups (P interaction = .86) and hazard ratios lower than 1 in black and white women, where analyses with limited numbers suggest somewhat greater reduction in black women (P interaction = .09). In summary, estrogen plus progestin and estrogen alone have opposite effects on breast cancer incidence, with no statistically significant interactions by race/ethnicity or BMI. Therefore, observational studies should not combine these two regimens when examining breast cancer risk.
| S-EPMC5943827 | biostudies-other
Project description:We evaluated the association between short-term change in body mass index (BMI) and breast density during a 1 year weight-loss intervention (Manchester, UK). We included 65 premenopausal women (35-45 years, ≥7 kg adult weight gain, family history of breast cancer). BMI and breast density (semi-automated area-based, automated volume-based) were measured at baseline, 1 year, and 2 years after study entry (1 year post intervention). Cross-sectional (between-women) and short-term change (within-women) associations between BMI and breast density were measured using repeated-measures correlation coefficients and multivariable linear mixed models. BMI was positively correlated with dense volume between-women (r = 0.41, 95%CI: 0.17, 0.61), but less so within-women (r = 0.08, 95%CI: -0.16, 0.28). There was little association with dense area (between-women r = -0.12, 95%CI: -0.38, 0.16; within-women r = 0.01, 95%CI: -0.24, 0.25). BMI and breast fat were positively correlated (volume: between r = 0.77, 95%CI: 0.69, 0.84, within r = 0.58, 95%CI: 0.36, 0.75; area: between r = 0.74, 95%CI: 0.63, 0.82, within r = 0.45, 95%CI: 0.23, 0.63). Multivariable models reported similar associations. Exploratory analysis suggested associations between BMI gain from 20 years and density measures (standard deviation change per +5 kg/m2 BMI: dense area: +0.61 (95%CI: 0.12, 1.09); fat volume: -0.31 (95%CI: -0.62, 0.00)). Short-term BMI change is likely to be positively associated with breast fat, but we found little association with dense tissue, although power was limited by small sample size.
| S-EPMC8269424 | biostudies-literature
Project description:Previous studies suggest that the association between mammographic density (MD) and breast cancer risk might be modified by other breast cancer risk factors. In this study, we assessed multiplicative interactions between MD measures and established risk factors on the risk of invasive breast cancer overall and according to menopausal and estrogen receptor status. We used data on 2,137 cases and 4,346 controls from a nested case-control study within the Nurses' Health Study (1976-2004) and Nurses' Health Study II (1989-2007), whose data on percent mammographic density (PMD) and absolute area of dense tissue and nondense tissue (NDA) were available. No interaction remained statistically significant after adjusting for number of comparisons. For breast cancer overall, we observed nominally significant interactions (P < 0.05) between nulliparity and PMD/NDA, age at menarche and area of dense tissue, and body mass index and NDA. Individual nominally significant interactions across MD measures and risk factors were also observed in analyses stratified by either menopausal or estrogen receptor status. Our findings help provide further insights into potential mechanisms underlying the association between MD and breast cancer.
| S-EPMC7946796 | biostudies-literature