UNASSIGNED: Breast cancer is the most frequent cancer in women, with significant mortality. Mammography is a routine investigation for breast disease. A known risk factor for breast cancer is increased breast density. Here, we tried to observe if mammographic density also affects the hormone receptor status of breast cancer, which will help in the understanding of the biological mechanisms of breast cancer development.
UNASSIGNED: Suspected breast cancer patients at Lok Nayak Hospital, Delhi, underwent mammography in the Department of Radiodiagnosis. The density of breast contralateral to the mass was assessed using Hologic Quantra software version 2.1.1 [Area Breast Density(ABD)]. The hormone receptor status of all the tumours was recorded on histopathology. Of these, 100 confirmed cases were included in the study.
UNASSIGNED: ER-positive, PR-positive, and HER2-positive tumours were seen in 41%, 33%, and 34% patients, respectively. Regarding ER receptor status, the mean ABD for positive and negative tumours was 27% and 23%, respectively, p-value = 0.01, showing significant relation between them. Mean ABD for HER2-positive and -negative tumours was 25% and 24%, respectively, p-value = 0.75. Mean ABD for PR-positive and PR-negative tumours was 23% and 25%, respectively, p-value = 0.42 (not significant).
UNASSIGNED: We found that ER-positive tumours were common in dense breasts, which was statistically significant. However, this was not true for PR and HER2 receptor status. Limited studies have been done to study MD using computerised software and its effect on hormone receptor status, with conflicting results. Further, large, multicentric studies can be useful in understanding the mechanism and providing better treatment for breast cancer patients.

OBJECTIVE: To assess the performance of breast cancer screening by category of breast density and age in a UK screening cohort.
METHODS: Raw full-field digital mammography data from a single site in the UK, forming a consecutive 3-year cohort of women aged 50 to 70 years from 2016 to 2018, were obtained retrospectively. Breast density was assessed using Volpara software. Examinations were grouped by density category and age group (50-60 and 61-70 years) to analyse screening performance. Statistical analysis was performed to determine the association between density categories and age groups. Volumetric breast density was assessed as a binary classifier of interval cancers (ICs) to find an optimal density threshold.
RESULTS: Forty-nine thousand nine-hundred forty-eight screening examinations (409 screen-detected cancers (SDCs) and 205 ICs) were included in the analysis. Mammographic sensitivity, SDC/(SDC + IC), decreased with increasing breast density from 75.0% for density a (p = 0.839, comparisons made to category b), to 73.5%, 59.8% (p = 0.001), and 51.3% (p < 0.001) in categories b, c, and d, respectively. IC rates were highest in the densest categories with rates of 1.8 (p = 0.039), 3.2, 5.7 (p < 0.001), and 7.9 (p < 0.001) per thousand for categories a, b, c, and d, respectively. The recall rate increased with breast density, leading to more false positive recalls, especially in the younger age group. There was no significant difference between the optimal density threshold found, 6.85, and that Volpara defined as the b/c boundary, 7.5.
CONCLUSIONS: The performance of screening is significantly reduced with increasing density with IC rates in the densest category four times higher than in women with fatty breasts. False positives are a particular issue for the younger subgroup without prior examinations.
CONCLUSIONS: In women attending screening there is significant underdiagnosis of breast cancer in those with dense breasts, most marked in the highest density category but still three times higher than in women with fatty breasts in the second highest category.
CONCLUSIONS: Breast density can mask cancers leading to underdiagnosis on mammography. Interval cancer rate increased with breast density categories \'a\' to \'d\'; 1.8 to 7.9 per thousand. Recall rates increased with increasing breast density, leading to more false positive recalls.

OBJECTIVE: Breast cancer is an important health problem, like obesity and dyslipidemia, with a strong association between body mass index (BMI) and breast cancer incidence and mortality. The risk of breast cancer is also high in women with high mammographic breast density (MBD). The purpose of this study was to analyze the association between BMI and MBD according to breast cancer molecular subtypes.
METHODS: This transversal, descriptive, multicenter study was conducted at three Spanish breast cancer units from November 2019 to October 2020 in women with a recent diagnosis of early breast cancer. Data were collected at the time of diagnosis.
RESULTS: The study included 162 women with a recent diagnosis of early breast cancer. The median age was 52 years and 49.1% were postmenopausal; 52% had normal weight, 32% overweight, and 16% obesity. There was no association between BMI and molecular subtype but, according to menopausal status, BMI was significantly higher in postmenopausal patients with luminal A (p = 0.011) and HER2-positive (p = 0.027) subtypes. There was no association between MBD and molecular subtype, but there were significant differences between BMI and MBD (p < 0.001), with lower BMI in patients with higher MBD. Patients with higher BMI had lower HDL-cholesterol (p < 0.001) and higher insulin (p < 0.001) levels, but there were no significant differences in total cholesterol or vitamin D.
CONCLUSIONS: This study showed higher BMI in luminal A and HER2-positive postmenopausal patients, and higher BMI in patients with low MBD regardless of menopausal status.

Tamoxifen prevents recurrence of breast cancer and is also approved for preventive, risk-reducing, therapy. Tamoxifen alters the breast tissue composition and decreases the mammographic density. We aimed to test if baseline breast tissue composition influences tamoxifen-associated density change. This biopsy-based study included 83 participants randomised to 6 months daily intake of placebo, 20, 10, 5, 2.5, or 1 mg tamoxifen. The study is nested within the double-blinded tamoxifen dose-determination trial Karolinska Mammography Project for Risk Prediction of Breast Cancer Intervention (KARISMA) Study. Ultrasound-guided core-needle breast biopsies were collected at baseline before starting treatment. Biopsies were quantified for epithelial, stromal, and adipose distributions, and epithelial and stromal expression of proliferation marker Ki67, oestrogen receptor (ER) and progesterone receptor (PR). Mammographic density was measured using STRATUS. We found that greater mammographic density at baseline was positively associated with stromal area and inversely associated with adipose area and stromal expression of ER. Premenopausal women had greater mammographic density and epithelial tissue, and expressed more epithelial Ki67, PR, and stromal PR, compared to postmenopausal women. In women treated with tamoxifen (1-20 mg), greater density decrease was associated with higher baseline density, epithelial Ki67, and stromal PR. Women who responded to tamoxifen with a density decrease had on average 17% higher baseline density and a 2.2-fold higher PR expression compared to non-responders. Our results indicate that features in the normal breast tissue before tamoxifen exposure influences the tamoxifen-associated density decrease, and that the age-associated difference in density change may be related to age-dependant differences in expression of Ki67 and PR.

BACKGROUND: Benign breast disease (BBD) and high mammographic breast density (MBD) are prevalent and independent risk factors for invasive breast cancer. It has been suggested that temporal changes in MBD may impact future invasive breast cancer risk, but this has not been studied among women with BBD.
METHODS: We undertook a nested case-control study within a cohort of 15,395 women with BBD in Kaiser Permanente Northwest (KPNW; 1970-2012, followed through mid-2015). Cases (n = 261) developed invasive breast cancer > 1 year after BBD diagnosis, whereas controls (n = 249) did not have breast cancer by the case diagnosis date. Cases and controls were individually matched on BBD diagnosis age and plan membership duration. Standardized %MBD change (per 2 years), categorized as stable/any increase (≥ 0%), minimal decrease of less than 5% or a decrease greater than or equal to 5%, was determined from baseline and follow-up mammograms. Associations between MBD change and breast cancer risk were examined using adjusted unconditional logistic regression.
RESULTS: Overall, 64.5% (n = 329) of BBD patients had non-proliferative and 35.5% (n = 181) had proliferative disease with/without atypia. Women with an MBD decrease (≤ - 5%) were less likely to develop breast cancer (Odds Ratio (OR) 0.64; 95% Confidence Interval (CI) 0.38, 1.07) compared with women with minimal decreases. Associations were stronger among women ≥ 50 years at BBD diagnosis (OR 0.48; 95% CI 0.25, 0.92) and with proliferative BBD (OR 0.32; 95% CI 0.11, 0.99).
CONCLUSIONS: Assessment of temporal MBD changes may inform risk monitoring among women with BBD, and strategies to actively reduce MBD may help decrease future breast cancer risk.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

Identifying biological drivers of mammographic breast density (MBD), a strong risk factor for breast cancer, could provide insight into breast cancer etiology and prevention. Studies on dietary factors and MBD have yielded conflicting results. There are, however, very limited data on the associations of dietary biomarkers and MBD.
We aimed to investigate the associations of vitamins and related cofactor metabolites with MBD in premenopausal women.
We measured 37 vitamins and related cofactor metabolites in fasting plasma samples of 705 premenopausal women recruited during their annual screening mammogram at the Washington University School of Medicine, St. Louis, MO. Volpara was used to assess volumetric percent density (VPD), dense volume (DV), and nondense volume (NDV). We estimated the least square means of VPD, DV, and NDV across quartiles of each metabolite, as well as the regression coefficient of a metabolite in continuous scale from multiple covariate-adjusted linear regression. We corrected for multiple testing using the Benjamini-Hochberg procedure to control the false discover rate (FDR) at a 5% level.
Participants\' mean VPD was 10.5%. Two vitamin A metabolites (β-cryptoxanthin and carotene diol 2) were positively associated, and one vitamin E metabolite (γ-tocopherol) was inversely associated with VPD. The mean VPD increased across quartiles of β-cryptoxanthin (Q1 = 7.2%, Q2 = 7.7%, Q3 = 8.4%%, Q4 = 9.2%; P-trend = 1.77E-05, FDR P value = 1.18E-03). There was a decrease in the mean VPD across quartiles of γ-tocopherol (Q1 = 9.4%, Q2 = 8.1%, Q3 = 8.0%, Q4 = 7.8%; P -trend = 4.01E-03, FDR P value = 0.04). Seven metabolites were associated with NDV: 3 vitamin E (γ-CEHC glucuronide, δ-CEHC, and γ-tocopherol) and 1 vitamin C (gulonate) were positively associated, whereas 2 vitamin A (carotene diol 2 and β-cryptoxanthin) and 1 vitamin C (threonate) were inversely associated with NDV. No metabolite was significantly associated with DV.
We report novel associations of vitamins and related cofactor metabolites with MBD in premenopausal women.

UNASSIGNED: Our purpose was to investigate the association between Mammographic breast density (MBD), a known strong marker for breast cancer and metformin and aspirin use and duration of use alone or simultaneously, in a sample of Iranian women considering other confounding factors.
UNASSIGNED: In a cross-sectional study, 712 individuals were selected out of women referred to two university hospitals for screening mammography. Participants\' information was collected with a questionnaire. Four-category density scale (a = almost entirely fatty, b = scattered fibroglandular densities, c= heterogeneously dense, and d = extremely dense) was categorized as low (a&b) and high (c&d) density.
UNASSIGNED: The mean age of the participants was 49.80 ± 7.26 years. Sixty-five percent of women belonged to the high and 35% to the low MBD category. Both aspirin and metformin had a significantly negative association with MBD, however, when confounding factors were entered into the models, only aspirin after adjustment for age and BMI had an inverse association with MBD (OR = 0.53, 95% CI: 0.35-0.94). Simultaneous use of metformin and aspirin (OR = 0.44, 95 %CI: 0.17-1.12) was associated with lower MBD. Furthermore, in women who used metformin (OR = 0.23, 95% CI: 0.09-0.62) and aspirin (OR= 0.35, 95% CI: 0.17-0.72) for 2 to 5 years, MBD was significantly lower. However, after the adjustment of confounding factors, these associations were not statistically significant.
UNASSIGNED: It seems metformin and aspirin intakes are associated with MBD. However, further studies with more sample size are needed.

High 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.
Premenopausal 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.
Of 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.
We report novel lipid species that are associated with MBD in premenopausal women. Studies are needed to validate our results and the translational potential.

UNASSIGNED: High mammographic breast density (MBD) is an independent breast cancer risk factor. In organised breast screening settings, discussions are ongoing regarding the optimal clinical role of MBD to help guide screening decisions. The aim of this scoping review was to provide an overview of current practices incorporating MBD within population-based breast screening programmes and from professional organisations internationally.
UNASSIGNED: This scoping review was conducted in accordance with the framework proposed by the Joanna Briggs Institute. The electronic databases, MEDLINE (PubMed), EMBASE, CINAHL Plus, Scopus, and Web of Science were systematically searched. Grey literature sources, websites of international breast screening programmes, and relevant government organisations were searched to identify further relevant literature. Data from identified materials were extracted and presented as a narrative summary.
UNASSIGNED: The search identified 78 relevant documents. Documents were identified for breast screening programmes in 18 countries relating to screening intervals for women with dense breasts, MBD measurement, reporting, notification, and guiding supplemental screening. Documents were identified from 18 international professional organisations with the majority of material relating to supplemental screening guidance for women with dense breasts. Key factors collated during the data extraction process as relevant considerations for MBD practices included the evidence base needed to inform decision-making processes and resources (healthcare system costs, radiology equipment, and workforce planning).
UNASSIGNED: This scoping review summarises current practices and guidelines incorporating MBD in international population-based breast screening settings and highlights the absence of consensus between organised breast screening programmes incorporating MBD in current breast screening protocols.