Breast Density In Postmenopausal Women Research Articles

Cigarette smoking and mammographic breast density in post-menopausal women from the EPIC Florence cohort.

Cigarette smoking has been recognized as a risk factor for breast cancer (BC) also if the biological mechanism remains poorly understood. High mammographic breast density (MBD) is associated with BC risk and many BC risk factors, such as genetic, anthropometric, reproductive and lifestyle factors and age, are also able to modulate MBD. The aim of the present study was to prospectively explore, in post-menopausal women, the association between smoking habits and MBD, assessed using an automated software, considering duration and intensity of smoking. The analysis was carried out in 3,774 women enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) Florence cohort in 1993-98, participating in the 2004-06 follow up (FU) and with at least one full-field digital mammography (FFDM) performed after FU. For each woman, detailed information on smoking habits, anthropometry, lifestyle and reproductive history was collected at enrollment and at FU. Smoking information at baseline and at FU was integrated. The fully automated Volpara™ software was used to obtain total breast volume (cm3), absolute breast dense volume (DV, cm3) and volumetric percent density (VPD, %) from the first available FFDM (average 5.3 years from FU). Multivariable linear regression models were applied to evaluate the associations between smoking habits and VPD or DV. An inverse association between smoking exposure and VPD emerged (Diff% -7.96%, p <0.0001 for current smokers and -3.92%, p 0.01 for former smokers, compared with non-smokers). An inverse dose-response relationship with number of cigarettes/day, years of smoking duration and lifetime smoking exposure (pack-years) and a direct association with time since smoking cessation among former smokers emerged. Similar associations, with an attenuated effect, emerged when DV was considered as the outcome variable. This longitudinal study confirms the inverse association between active smoking, a known risk factor for BC, and MBD among post-menopausal women. The inclusion of smoking habits in the existing BC risk prediction models could be evaluated in future studies.

Factors Associated with Longitudinal Changes in Mammographic Density in a Multiethnic Breast Screening Cohort of Postmenopausal Women.

Breast density is an important risk factor for breast cancer and is known to be associated with characteristics such as age, race, and hormone levels; however, it is unclear what factors contribute to changes in breast density in postmenopausal women over time. Understanding factors associated with density changes may enable a better understanding of breast cancer risk and facilitate potential strategies for prevention. This study investigated potential associations between personal factors and changes in mammographic density in a cohort of 3,392 postmenopausal women with no personal history of breast cancer between 2011 and 2017. Self-reported information on demographics, breast and reproductive history, and lifestyle factors, including body mass index (BMI), alcohol intake, smoking, and physical activity, was collected by an electronic intake form, and breast imaging reporting and database system (BI-RADS) mammographic density scores were obtained from electronic medical records. Factors associated with a longitudinal increase or decrease in mammographic density were identified using Fisher's exact test and multivariate conditional logistic regression. 7.9% of women exhibited a longitudinal decrease in mammographic density, 6.7% exhibited an increase, and 85.4% exhibited no change. Longitudinal changes in mammographic density were correlated with age, race/ethnicity, and age at menopause in the univariate analysis. In the multivariate analysis, Asian women were more likely to exhibit a longitudinal increase in mammographic density and less likely to exhibit a decrease compared to White women. On the other hand, obese women were less likely to exhibit an increase and more likely to exhibit a decrease compared to normal weight women. Women who underwent menopause at age 55 years or older were less likely to exhibit a decrease in mammographic density compared to women who underwent menopause at a younger age. Besides obesity, lifestyle factors (alcohol intake, smoking, and physical activity) were not associated with longitudinal changes in mammographic density. The associations we observed between Asian race/obesity and longitudinal changes in BI-RADS density in postmenopausal women are paradoxical in that breast cancer risk is lower in Asian women and higher in obese women. However, the association between later age at menopause and a decreased likelihood of decreasing in BI-RADS density over time is consistent with later age at menopause being a risk factor for breast cancer and suggests a potential relationship between greater cumulative lifetime estrogen exposure and relative stability in breast density after menopause. Our findings support the complexity of the relationships between breast density, BMI, hormone exposure, and breast cancer risk.

Lifetime changes in body fatness and breast density in postmenopausal women: the FEDRA study

BackgroundHigh mammographic breast density (MBD) is an established risk factor for breast cancer (BC). Body fatness conveys an increased BC risk in postmenopause but is associated with less dense breasts. Here, we studied the relationship between body fatness and breast composition within the FEDRA (Florence-EPIC Digital mammographic density and breast cancer Risk Assessment) longitudinal study.MethodsRepeated anthropometric data and MBD parameters (obtained through an automated software on BC screening digital mammograms) were available for all participants, as well as information on other BC risk factors. Multivariate linear regression and functional data analysis were used to longitudinally evaluate the association of body fatness, and changes thereof over time, with dense (DV) and non-dense (NDV) breast volumes and volumetric percent density (VPD).ResultsA total of 5,262 women were included, with anthropometric data available at 20 and 40 years of age, at EPIC baseline (mean 49.0 years), and an average of 9.4 years thereafter. The mean number of mammograms per woman was 3.3 (SD 1.6). Body fatness (and increases thereof) at any age was positively associated with DV and NDV (the association being consistently stronger for the latter), and inversely associated with VPD. For instance, an increase by 1 kg/year between the age of 40 years and EPIC baseline was significantly associated with 1.97% higher DV, 8.85% higher NDV, and 5.82% lower VPD.ConclusionBody fatness and its increase from young adulthood until midlife are inversely associated with volumetric percent density, but positively associated with dense and non-dense breast volumes in postmenopausal women.

Age at first full-term pregnancy and mammographic breast density in postmenopausal women: a systematic review

While mammographic breast density (MBD) is a well-established independent risk factor for breast cancer and age at first full-term pregnancy (FFTP) has been identified as a protective factor, there are very few high-quality studies that address the relationship between these two variables. The goal of this work was to generate a systematic review of published studies that addresses the association between age at FFTP and MBD based on objective mammographic findings in postmenopausal women. The English-language literature published with a cutoff date 31 August 2022 in the PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library databases was searched using relevant keywords. The Newcastle-Ottawa Quality Assessment Scale was used to assess the quality of all relevant studies identified in this search. Our search yielded 12 original publications (including one conference abstract) that focused on the impact of age at FFTP on MBD in studies that objectively evaluated this condition in women without any form of breast pathology. Of these, six studies revealed a direct association between older age at FFTP and higher MBD in postmenopausal women. The remaining six studies reported either no relationship between these parameters or revealed an inverse association between MBD and older age at FFTP. We concluded that half of the currently-published findings supported an association between older age at FFTP and higher MBD. However, substantial heterogeneity between FFTP and MBD might be explained by different racial clusters, lacking specific information of other reproductive factors and differences in methodology utilized. The goal of this work was to examine whether age at FFTP is associated with MBD in postmenopausal women.

Hormone and receptor activator of NF-\u03baB (RANK) pathway gene expression in plasma and mammographic breast density in postmenopausal women

BackgroundHormones impact breast tissue proliferation. Studies investigating the associations of circulating hormone levels with mammographic breast density have reported conflicting results. Due to the limited number of studies, we investigated the associations of hormone gene expression as well as their downstream mediators within the plasma with mammographic breast density in postmenopausal women.MethodsWe recruited postmenopausal women at their annual screening mammogram at Washington University School of Medicine, St. Louis. We used the NanoString nCounter platform to quantify gene expression of hormones (prolactin, progesterone receptor (PGR), estrogen receptor 1 (ESR1), signal transducer and activator of transcription (STAT1 and STAT5), and receptor activator of nuclear factor-kB (RANK) pathway markers (RANK, RANKL, osteoprotegerin, TNFRSF18, and TNFRSF13B) in plasma. We used Volpara to measure volumetric percent density, dense volume, and non-dense volume. Linear regression models, adjusted for confounders, were used to evaluate associations between gene expression (linear fold change) and mammographic breast density.ResultsOne unit increase in ESR1, RANK, and TNFRSF18 gene expression was associated with 8% (95% CI 0–15%, p value = 0.05), 10% (95% CI 0–20%, p value = 0.04) and % (95% CI 0–9%, p value = 0.04) higher volumetric percent density, respectively. There were no associations between gene expression of other markers and volumetric percent density. One unit increase in osteoprotegerin and PGR gene expression was associated with 12% (95% CI 4–19%, p value = 0.003) and 7% (95% CI 0–13%, p value = 0.04) lower non-dense volume, respectively.ConclusionThese findings provide new insight on the associations of plasma hormonal and RANK pathway gene expression with mammographic breast density in postmenopausal women and require confirmation in other studies.

Changes in adiposity over the life course and gene expression in postmenopausal women.

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.

Plasma Growth Factor Gene Expression and Mammographic Breast Density in Postmenopausal Women.

Mammographic breast density is a strong risk factor for breast cancer. Understanding its underlying biological mechanisms could have utility in breast cancer prevention.

Abstract PS7-32: Age of first full term pregnancy and other reproductive factors affect mammographic breast density in postmenopausal women

Abstract The objective of this study is to determine the role of age at first full term pregnancy (FFTP), and mammographic breast density (MBD) in postmenopausal women. For this purpose women, age 50-69y, participating in the Flemish (Belgium) population based breast cancer screening program were invited to participate in the study during their visit at the mammography department in the University Hospital Leuven (UZLeuven) or at the mobile unit of their hometown. A self-administered questionnaire providing detailed information on lifestyle and environmental exposure was completed by the participants. In this analysis 1,034 women were included (mean age of 59.1 years (range: 49.2 to 69.8). The three parameters of MBD were the percentage glandular tissue of the total breast volume (GLAND), the ratio of the glandular tissue volume compared to the whole breast volume or Volumetric Breast Density (VBD) and the BI-RADS density classification (VolparaDataManager®, USA). The first two parameters (GLAND and VBD) were transformed according to the natural logarithm to improve normality. These two parameters were linked with the FFTP via a piecewise linear regression (PLR) model using the NLIN procedure in SAS (version 9.4, SAS Institute, Cary, NC, USA). For the BI-RADS, we used ordinal logistic regression analysis. All models were corrected for a priori chosen variables: age at menarche, the ever use of oral contraceptive pill (OC), hormonal use at menopause, age at MBD measurement, and the body mass index at participation. Estimates are provided as a % change (95% confidence intervals [CI]).The average age at FFTP was 26.1 years (5th-95th percentile: 20 to 34). The PLR model estimated the breakpoint in our analysis at a FFTP of 25.7 years (95% CI: 22.3 to 29.1). For the woman with a FFTP younger than 25.7 years, the association between GLAND or VBD and FFTP is statistically not significant. For woman with a FFTP above 25.7 years, each year increase in FFTP was associated with 1.3% increase in GLAND (95% CI: 0.0% to 2.5%) and 1.5% increase in VBD (95% CI: 0.2% to 2.8%). Analysis of the BI-RADS showed similar results, the odds of belonging to a higher BI-RADS classification (e.g. from class 1 to class 2) increased with 5.4% (95% CI: 0.0% to 11.0%) for each year increase in FFTP age after the age of 25.7 years. Among other reproductive factors such as age at menarche, for every year delay there is 3.5% higher GLAND (95% CI: 1.4 % to 5.6%) and 2.5% higher VBD (95% CI: 0.5% to 4.6%) and the ever use of OC resulted in 10.0 % decrease in GLAND (95% CI: -18.8% to -0.2%) and 10.2% decrease in VBD (95%CI:-19.1% to -0.3%).In conclusion, this study is to our knowledge the first one to show that mammographic breast density is significantly increased when pregnancy takes place after 25.7 years of age. Later age at menarche is increasing and use of oral contraceptive is reducing mammographic breast density at postmenopause. (This study was supported by a Grant of the Breast Cancer Organization Think Pink of Belgium, the Department of Breast Radiology and Mobile Unit of the University Hospital Leuven, the Centre of Environmental Sciences and the Centre of Biostatistics of the Hasselt University, and NIH Grant CA06927 to FCCC, PA, USA). Citation Format: Magda Johanna Vandeloo, Kristof Y. Neven, Liesbeth M. Bruckers, Jose Russo, Liesbeth Vancoillie, Esmee M. Bijnens, Eliane Kellen, Tim S. Nawrot, Chantal Van Ongeval. Age of first full term pregnancy and other reproductive factors affect mammographic breast density in postmenopausal women [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-32.

Abstract 1158: Hormone gene expression and mammographic breast density in postmenopausal women

Abstract Introduction: Mammographic breast density (MBD), which reflects the amount of epithelial and stromal tissues relative to adipose tissue in the breast, is a strong risk factor for breast cancer. MBD declines with menopause, highlighting the role of endogenous hormones. Nevertheless, studies evaluating the associations of circulating hormone levels with MBD report conflicting results. Only a limited number of studies have addressed the genomic signatures of MBD, which may better capture the broader transcriptional changes associated with MBD and more accurately quantify hormonal exposure than circulating hormone levels. We therefore investigated the associations of hormonal gene expression with MBD in postmenopausal women. Methods: We recruited 368 mid-life postmenopausal women (ages 50-64 years) who had annual screening mammogram at Washington University School of Medicine, St. Louis, MO between October 2017 and September 2018. Each participant completed a blood draw and a questionnaire on breast cancer risk factors. We used Volpara software to measure volumetric percent density (VPD, %), dense volume (VD, cm3) and non-dense volume (NDV, cm3). Prolactin (PRL), progesterone (PGR), estrogen receptor 1 (ESR1), signal transducer and activator of transcription (STAT1), and STAT5 gene expression were measured in total RNA isolated from plasma using NanoString nCounter system. Statistical analyses were performed with the NanoString nSolver Analysis Software. Fold changes in gene expression and p-values were calculated using nCounter default settings. Analyses were adjusted for body mass index (BMI), age, age at menarche, parity/age at first birth, race, and menopausal hormone use. VPD, DV, and NDV were log10 transformed to ensure the normality of the residuals. Results: The mean age of study participants was 57.9 years. The mean BMI was 31.3kg/m2. The average VPD, DV, and NDV were 6.2%, 121.2 cm3, and 2134.4 cm3, respectively. There were strong correlations between STAT1 and STAT5 gene expression (r=0.59, p-value&amp;lt;0.0001), and moderate correlations between ESR1 and PGR gene expression (r=0.43, p-value&amp;lt;0.0001). ESR1 gene expression was associated with VPD, while PGR and STAT5 were marginally associated with NDV. One unit increase in ESR1 gene expression was associated with a 29% (95% CI 2-64%) increase in VPD (p-value=0.03). One unit increase in STAT5 gene expression was associated with an 8% (p-value=0.05) increase in NDV, while one unit increase in PGR gene expression was associated with a 20% (p-value=0.06) decrease in NDV. Hormone gene expression was not associated with DV. Conclusions: We provide novel data on the associations of endogenous hormone gene expression with MBD in postmenopausal women. Future studies characterizing transcriptomic changes in hormone signaling and MBD are needed, as targeting these pathways could be used to reduce MBD for breast cancer prevention. Citation Format: Rachel L. Mintz, Mei Wang, Shuai Xu, Chris Markovic, Adetunji T. Toriola. Hormone gene expression and mammographic breast density in postmenopausal women [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1158.

Adiposity Change Over the Life Course and Mammographic Breast Density in Postmenopausal Women.

Mammographic breast density is a strong risk factor for breast cancer. We comprehensively investigated the associations of body mass index (BMI) change from ages 10, 18, and 30 to age at mammogram with mammographic breast density in postmenopausal women. We used multivariable linear regression models, adjusted for confounders, to investigate the associations of BMI change with volumetric percent density, dense volume, and nondense volume, assessed using Volpara in 367 women. At the time of mammogram, the mean age was 57.9 years. Compared with women who had a BMI gain of 0.1-5 kg/m2 from age 10, women who had a BMI gain of 5.1-10 kg/m2 had a 24.4% decrease [95% confidence interval (CI), 6.0%-39.2%] in volumetric percent density; women who had a BMI gain of 10.1-15 kg/m2 had a 46.1% decrease (95% CI, 33.0%-56.7%) in volumetric percent density; and women who had a BMI gain of >15 kg/m2 had a 56.5% decrease (95% CI, 46.0%-65.0%) in volumetric percent density. Similar, but slightly attenuated associations were observed for BMI gain from ages 18 and 30 to age at mammogram and volumetric percent density. BMI gain over the life course was positively associated with nondense volume, but not dense volume. We observed strong associations between BMI change over the life course and mammographic breast density. The inverse associations between early-life adiposity change and volumetric percent density suggest that childhood adiposity may confer long-term protection against postmenopausal breast cancer via its effect of mammographic breast density.

Abstract A23: Association of gut microbiome diversity with obesity and breast density in postmenopausal women

Abstract Purpose: The plausible roles of the gut microbiome (GM) in obesity as well as breast cancer have been discussed in recent reviews. The associations of GM with mammographic breast density (BD), a well-established strong breast cancer risk factor, also associated with body mass index (BMI), are poorly studied. We examined GM profiles in relation to BD and BMI in a sample of healthy postmenopausal women. Methods: Women were recruited in mammography clinics at Moffitt Cancer Center and via recruitment announcements at the University of Florida. Eligible women were postmenopausal, had a BMI ≤35 kg/m2, and had not taken oral/IV antibiotics within 30 days and/or more than two separate antibiotic regimens within the previous three months. All women provided a fecal sample and comprehensive information on breast cancer risk factors including body weight and height. Mammographic BD was available for 69 women recruited at Moffitt and was classified according to the American College of Radiology’s BI-RADS BD classification system. For this analysis, BD was dichotomized as low (BI-RADS I or II) or high (BI-RADS III and IV). DNA was isolated from fecal samples and the V1-V2 hypervariable regions of 16S rRNA amplified using barcoded primers for sequencing on the Illumina MiSeq platform. Chao1, Inverse Simpson, and Shannon indices were used to classify within sample diversity. The two-sample Wilcoxon test was used to examine associations of GM with BD and BMI. Associations were also examined according to the ratio of the two main phyla in the human GM (Firmicutes and Bacteroidetes; F/B ratio) that has been linked to obesity in previous studies. Results: Among 69 women with BD data, 39 had low BD and 30 had high BD. BMI was inversely associated with BD (mean BMI=23.8 in women with high BD and BMI=28.0 in women with low BD, p=1.07 × 10-5). The F/B ratio was not associated with BMI (median F/B ratio=0.90, 0.84, and 0.96 for normal weight, overweight, and obesity, respectively, p=0.57). Similar levels of diversity were found across weight groups according to the Shannon (4.05, 3.97, and 3.96, respectively, p=0.83); inverse Simpson (20.6, 20.1, and 19.3, respectively, p=0.97); and chao1 (433, 441, and 419, respectively, p=0.31) indices. F/B ratio and microbiota diversity were both suggestively greater in women with high vs. low BD (median F/B ratio=1.15 for high and 0.94 for low BD, p=0.35; Shannon index: 4.24 for high and 4.15 for low BD, p=0.14; inverse Simpson= 25.3 for high and 21.0 for low BD, p=0.15; chao1= 519 for high and 429 for low BD, p=0.17). Highest levels of alpha diversity were observed in women who had both high BD and low BMI. Taxonomic families that distinguished women with high vs. low BD included Ruminococcaceae, Mogibacteriaceae, Bacteroidaceae, Lachnospiraceae, Christensenellaceae, and Coriobacteriaceae. Conclusion: Results suggest that women with high and low BD may differ with respect to GM alpha diversity and GM composition. Citation Format: Lusine Yaghjyan, Xuefeng Wang, Maria Ukhanova, Yessica Martinez, Shannan Rich, Volker Mai, Kathleen Egan. Association of gut microbiome diversity with obesity and breast density in postmenopausal women [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A23.

Does metformin affect mammographic breast density in postmenopausal women with type 2 diabetes

Background: Increased mammographic breast density (MBD) is known to be associated with an increased risk of developing breast cancer.Aims: In this study, we aimed to research the possible relationship between MBD and metformin use in postmenopausal women diagnosed with type 2 diabetes mellitus (T2DM).Method: The patients were divided into two groups: women with T2DM and who were on metformin and women who were newly diagnosed with T2DM and had not yet taken metformin. MBD types are evaluated by a specialist radiologist.Results: Among the 74 women, 32 (43.2%) were in the group that did not use metformin and 42 (56.8%) were in the group of patients using metformin. The duration of breastfeeding (p = .0003), fasting blood glucose (p = .0003) and HbA1c (p = .0006) were statistically significantly higher in the group not using metformin. The quantitative mean ranks of the group members’ MBD’s were 41.81 in the metformin naïve group and 34.21 in the group using metformin (p = .12).Conclusions: In conclusion, metformin has no statistically significant effect on MBD in postmenopausal female patients with T2DM.

Postmenopausal Dense Breasts Maintain Premenopausal Levels of GH and Insulin-like Growth Factor Binding Proteins in Vivo.

Dense breast tissue is associated with 4 to 6 times higher risk of breast cancer by poorly understood mechanisms. No preventive therapy for this high-risk group is available. After menopause, breast density decreases due to involution of the mammary gland. In dense breast tissue, this process is haltered by undetermined biological actions. Growth hormone (GH) and insulin-like binding proteins (IGFBPs) play major roles in normal mammary gland development, but their roles in maintaining breast density are unknown. To reveal in vivo levels of GH, IGFBPs, and other pro-tumorigenic proteins in the extracellular microenvironment in breast cancer, in normal breast tissue with various breast density in postmenopausal women, and premenopausal breasts. We also sought to determine possible correlations between these determinants. Microdialysis was used to collect extracellular in vivo proteins intratumorally from breast cancers before surgery and from normal human breast tissue from premenopausal women and postmenopausal women with mammographic dense or nondense breasts. Estrogen receptor positive breast cancers exhibited increased extracellular GH (P < .01). Dense breasts of postmenopausal women exhibited similar levels of GH as premenopausal breasts and significantly higher levels than in nondense breasts (P < .001). Similar results were found for IGFBP-1, -2, -3, and -7 (P < .01) and for IGFBP-6 (P <.05). Strong positive correlations were revealed between GH and IGFBPs and pro-tumorigenic matrix metalloproteinases, urokinase-type plasminogen activator, Interleukin 6, Interleukin 8, and vascular endothelial growth factor in normal breast tissue. GH pathways may be targetable for cancer prevention therapeutics in postmenopausal women with dense breast tissue.

Abstract 593: Mammographic breast density in postmenopausal women is affected by the age of first full term pregnancy

Abstract Mammographic breast density (MBD) is accepted as a risk factor in breast cancer, whereas age of first full term pregnancy (FFTP) has been demonstrated to be a protective one. The objective of this study is to investigate the association between reproductive history and MBD at menopause. Women, age 50-69y, participating in the Flemish (Belgium) governmental organised breast cancer screening program were invited to participate in the study during their visit at the mammography department in Leuven (hospital and the mobile unit). The study was approved by the ethical committee of the hospital. After signing the informed consent, a self-administered questionnaire (SAQ) providing information on lifestyle and environmental exposure was completed by the participants. In the present work we present the analysis of the first 640 women that completed the SAQ and underwent mammography. Questionnaire data were registered via the Qualtrics software. The three parameters of MBD (VolparaDataManager®, USA) included the percentage glandular tissue of the total breast volume (GLAND), the ratio of the glandular tissue volume compared to the whole breast volume or Volumetric Breast Density (VBD) and the BIRADS density classification. We applied linear regression models to investigate the association between the continuous breast density markers (GLAND and VBD, log transformed) and the following explanatory variables: age of woman, ever pregnant, number of pregnancies, age of FFTP, ever breastfed (BF), amount and duration of BF, and breastfeeding in FFTP. An ordinal logistic regression model was used for the breast density marker BIRADS. The average GLAND and VBD changes with a multiplicative factor of 1.073 (p = 0.013) and 1.072 (p = 0.013) for a 5-year increase of age of FFTP. Thus, an increase of 5 years in age of FFTP is associated with about 7% increase in geometric mean of GLAND and VBD. The odds ratio for a higher versus a lower score of the BIRADS classification is 1.24 (p = 0.023) greater for every 5-year increase in age of FFTP. These results are independent for the inverse association between the age of the woman and the MBD markers. For a 5 year increment in age, geometric GLAND (p = 0.019) and VBD (p = 0.024) are approximately 5% lower and the odds ratio for a higher BIRADS score is 12% higher (p = 0.079). There is no association between the MBD markers and breastfeeding, the number and duration BF, and the number of pregnancies after correcting for age and age of FFTP. In conclusion, this study is to our knowledge the first one to show that MBD is significantly reduced when pregnancy takes place at early age.( This study was supported by a Grant of the Breast Cancer Organization Think Pink of Belgium, the Department of Breast Radiology and Mobile Unit of the University Hospital Leuven, the Center of Environmental Sciences and the Center of Biostatistics of the Hasselt University, and NIH Grant CA06927 to FCCC, PA, USA.) Citation Format: Magda J. Vandeloo, Kristof Y. Neven, Liesbeth Bruckers, Jose Russo, Liesbeth Vancoullie, Esmée Bijnens, Eliane Kellen, Tim S. Nawrot, Chantal Van Ongeval. Mammographic breast density in postmenopausal women is affected by the age of first full term pregnancy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 593.

The Relation Between Metabolic Syndrome and Its Components with Breast Density in Postmenopausal Women.

Background: Metabolic syndrome (MetS) could lead to an increase in fatty tissue that could be seen as a radiolucent image depicting breast density (BD) by a mammogram. We aimed to investigate the association between MetS and its separate components with BD among naturally postmenopausal women. Materials and Methods: Data of 494 postmenopausal patients who were admitted to our outpatient clinic between December 2012 and July 2015 were retrospectively reviewed. A total of 279 patients were in the without MetS group and 215 patients were in the with MetS group. Average BD percentage of the left and right breasts were measured. Basic characteristics, laboratory, and mammography results between the without MetS and the with MetS groups were compared. Results: The mean age of the patients was 53.20 ± 6.67 years in the without MetS group and 55.41 ± 6.56 years in the with MetS group. There were 219 (78.5%) patients in the without MetS group and 187 (86.9%) patients in the with MetS group with lower BD. The without MetS group had significantly higher BD scores than those patients in the with MetS group (P = 0.02). In correlation analysis, there was a negative correlation between fasting plasma glucose (FPG), systolic and diastolic blood pressures, waist circumference (WC), and BD scores. However, there was a positive correlation between high-density lipoprotein (HDL) and BD score (P = 0.046). In multivariate logistic regression analysis, it is found that lower body mass index (BMI) and parity were significantly associated with higher BD (P = 0.002 and P = 0.001; respectively). Conclusion: The lower BMI and parity may be associated with higher BD in postmenopausal women. In addition, higher HDL and lower FPG, blood pressure, triglyceride, and WC may be correlated with higher BD.

Differential impact of body mass index on bone and breast density in post-menopausal women and potential implications for the risk of breast cancer

Differential impact of body mass index on bone and breast density in post-menopausal women and potential implications for the risk of breast cancer

Interactions of alcohol and postmenopausal hormone use in regards to mammographic breast density

We investigated the association of alcohol intake with mammographic breast density in postmenopausal women by their hormone therapy (HT) status. This study included 2,100 cancer-free postmenopausal women within the Nurses' Health Study and Nurses' Health Study II cohorts. Percent breast density (PD), absolute dense (DA), and non-dense areas (NDA) were measured from digitized film mammograms using a computer-assisted thresholding technique; all measures were square root transformed. Alcohol consumption was assessed with a food frequency questionnaire (0, < 5, and ≥ 5g/day). Information regarding breast cancer risk factors was obtained from baseline or biennial questionnaires closest to the mammogram date. We used generalized linear regression to examine associations between alcohol and breast density measures in women with no HT history, current, and past HT users. In multivariable analyses, we found no associations of alcohol consumption with PD (p trend = 0.32) and DA (p trend = 0.53) and an inverse association with NDA (β = - 0.41, 95% CI - 0.73, - 0.09 for ≥ 5g/day, p trend < 0.01). In the stratified analysis by HT status, alcohol was not associated with PD in any of the strata. We found a significant inverse association of alcohol with NDA among past HT users (β = - 0.79, 95% CI - 1.51, - 0.07 for ≥ 5g/day, p trend = 0.02). There were no significant interactions between alcohol and HT in relation to PD, DA, and NDA (p interaction = 0.19, 0.42, and 0.43, respectively). Our findings suggest that associations of alcohol with breast density do not vary by HT status.

The DAMA trial: a diet and physical activity intervention trial to reduce mammographic breast density in postmenopausal women in Tuscany, Italy. Study protocol and baseline characteristics.

Aims and background. High mammographic breast density (MBD) is an established risk factor for breast cancer (BC). The influence of diet and physical activity (PA) on MBD has long been investigated. In an observational study of a cohort in Florence, we observed inverse associations between consumption of vegetables and olive oil and moderate leisure-time PA and MBD, while high alcohol intake and high glycemic load diets were positively associated with MBD. We set out to investigate whether dietary and PA interventions were able to reduce MBD in postmenopausal women with high MBD (>50%). Methods and study design. The DAMA (Diet, physical Activity and MAmmography) trial, a factorial randomized trial involving healthy nonsmoking postmenopausal women not using hormone replacement therapy and having MBD >50%, is aimed at evaluating the ability of a 24-month intervention based on moderate-intensity PA and/or dietary modification focused on plant foods with a low glycemic load, low in saturated fats and alcohol, and rich in antioxidants and fiber, to reduce the percent MBD. Participants have been randomized to 1 of 4 study arms (diet, PA, diet + PA, control). Dietary and PA habits and anthropometry are collected at baseline and at the end of the intervention phase together with repeated blood and urine samples. The primary outcome of the study is the absolute change in percent MBD as assessed on baseline and follow-up digital mammograms performed in the framework of the local screening program. Results. Of 728 eligible women, 234 (32.1%) agreed to participate. We did not observe any difference across study arms in the baseline distribution of variables of interest related to diet and lifestyle. Conclusions. The DAMA trial may contribute to a better understanding of MBD determinants. This will provide insight into the pathogenesis of BC and may allow the development of strategies for primary prevention focused on high-MBD groups that are easily identifiable in large-scale BC screening programs. ISRCTN28492718.

Hyperlipidemia and Mammographic Breast Density in Post-menopausal Women

Hyperlipidemia and Mammographic Breast Density in Post-menopausal Women

Similar to Adiponectin, Serum Levels of Osteocalcin are Associated with Mammographic Breast Density in Postmenopausal Women.

Breast cancer is the most common type of cancer in Canadian women and worldwide. Mammographic density is a well-established breast cancer risk. Recent evidence suggested inverse correlations among adiponectin, osteocalcin, and the risk developing breast cancer. The objective of the study was to evaluate the relationship between breast density and adiponectin and osteocalcin concentrations. A cross-sectional study was performed in 239 women, age range 40 to 60. Mammographic density, serum adiponectin, and osteocalcin levels were measured. According to the Wolfe method, participants were divided into those with low-risk and high-risk pattern mammograms. The study population included 107 premenopausal and 132 postmenopausal women. Parameters were no different between women with low-risk and high-risk patterns. In obese postmenopausal women, the high-risk pattern mammogram group had significantly higher values of adiponectin and osteocalcin compared with the low-risk pattern group. Multiple linear regression analyses showed that adiponectin and osteocalcin levels were associated with high-risk pattern mammograms. Adiponectin and osteocalcin levels were directly associated with high-risk pattern mammograms in obese postmenopausal women. These results do not support the use of adipokines as biomarkers; nevertheless, the most important factor is to assess the risk through breast density.