Mammographic Breast Density In Postmenopausal Women Research Articles

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.

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<0.0001), and moderate correlations between ESR1 and PGR gene expression (r=0.43, p-value<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.

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.

Aromatase inhibitors and mammographic breast density in postmenopausal women receiving hormone therapy

One of the main concerns regarding long-term use of hormone therapy (HT) in symptomatic menopausal women is the perceived increased risk of breast cancer. A method to reduce breast cancer risk in this population of women is urgently needed. We hypothesized that adding aromatase inhibitors (AIs) to HT would reduce local breast estrogen exposure and breast cancer risk without altering the beneficial systemic effects of HT on menopausal symptoms or bone density. The aim of this study was to investigate the effect of AIs and HT on mammographic breast density (MBD) as a surrogate marker of breast cancer risk in postmenopausal women receiving low-dose HT. This was a retrospective cohort study conducted at private clinics affiliated with a university hospital. One group of postmenopausal women (n = 28) received low-dose HT daily plus letrozole 2.5 mg three times weekly. Postmenopausal women receiving HT alone (n = 28) served as controls. MBD, the primary outcome, was measured using quantitative image analysis software as well as by visual analysis by a radiologist. Hypoestrogenic effects, adverse reactions, and bone mineral densities were secondary outcome measures. The mammograms of 18 women in the study group and 22 women in the control group were suitable for comparison. A statistically significant reduction in MBD occurred in the women who received HT plus an AI, whereas no significant change was observed in the women receiving HT alone. There was no significant increase in hypoestrogenic symptoms during the use of AIs, and bone mineral densities were not significantly reduced. Adding an AI to HT may lower MBD in postmenopausal women. AIs could be good candidates for primary chemoprevention of breast cancer in postmenopausal women using HT.