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Purpose: 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. [ABSTRACT FROM AUTHOR]

Background: Despite known benefits of physical activity in reducing breast cancer risk, its impact on mammographic characteristics remain unclear and understudied. This study aimed to investigate associations between pre-diagnostic physical activity and mammographic features at breast cancer diagnosis, specifically mammographic breast density (MBD) and mammographic tumor appearance (MA), as well as mode of cancer detection (MoD). Methods: Physical activity levels from study baseline (1991–1996) and mammographic information from the time of invasive breast cancer diagnosis (1991–2014) of 1116 women enrolled in the Malmö Diet and Cancer Study cohort were used. Duration and intensity of physical activity were assessed according to metabolic equivalent of task hours (MET-h) per week, or World Health Organization (WHO) guideline recommendations. MBD was dichotomized into low-moderate or high, MA into spiculated or non-spiculated tumors, and MoD into clinical or screening detection. Associations were investigated through logistic regression analyses providing odds ratios (OR) with 95% confidence intervals (CI) in crude and multivariable-adjusted models. Results: In total, 32% of participants had high MBD at diagnosis, 37% had non-spiculated MA and 50% had clinical MoD. Overall, no association between physical activity and MBD was found with increasing MET-h/week or when comparing women who exceeded WHO guidelines to those subceeding recommendations (ORadj 1.24, 95% CI 0.78–1.98). Likewise, no differences in MA or MoD were observed across categories of physical activity. Conclusions: No associations were observed between pre-diagnostic physical activity and MBD, MA, or MoD at breast cancer diagnosis. While physical activity is an established breast cancer prevention strategy, it does not appear to modify mammographic characteristics or screening detection. [ABSTRACT FROM AUTHOR]

Abstract Background Despite known benefits of physical activity in reducing breast cancer risk, its impact on mammographic characteristics remain unclear and understudied. This study aimed to investigate associations between pre-diagnostic physical activity and mammographic features at breast cancer diagnosis, specifically mammographic breast density (MBD) and mammographic tumor appearance (MA), as well as mode of cancer detection (MoD). Methods Physical activity levels from study baseline (1991–1996) and mammographic information from the time of invasive breast cancer diagnosis (1991–2014) of 1116 women enrolled in the Malmö Diet and Cancer Study cohort were used. Duration and intensity of physical activity were assessed according to metabolic equivalent of task hours (MET-h) per week, or World Health Organization (WHO) guideline recommendations. MBD was dichotomized into low-moderate or high, MA into spiculated or non-spiculated tumors, and MoD into clinical or screening detection. Associations were investigated through logistic regression analyses providing odds ratios (OR) with 95% confidence intervals (CI) in crude and multivariable-adjusted models. Results In total, 32% of participants had high MBD at diagnosis, 37% had non-spiculated MA and 50% had clinical MoD. Overall, no association between physical activity and MBD was found with increasing MET-h/week or when comparing women who exceeded WHO guidelines to those subceeding recommendations (ORadj 1.24, 95% CI 0.78–1.98). Likewise, no differences in MA or MoD were observed across categories of physical activity. Conclusions No associations were observed between pre-diagnostic physical activity and MBD, MA, or MoD at breast cancer diagnosis. While physical activity is an established breast cancer prevention strategy, it does not appear to modify mammographic characteristics or screening detection.

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. [ABSTRACT FROM AUTHOR]

Abstract Introduction 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). Discussion 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.

Introduction: 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). Discussion: 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. [ABSTRACT FROM AUTHOR]

Introduction: 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. Methods: 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 fullfield 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. Results: 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. Discussion: 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. [ABSTRACT FROM AUTHOR]

IntroductionCigarette 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.MethodsThe 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.ResultsAn inverse association between smoking exposure and VPD emerged (Diff% -7.96%, p

Abstract Background 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. Methods 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

Background: 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. Methods: 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. Results: 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 (O R= 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. Conclusion: It seems metformin and aspirin intakes are associated with MBD. However, further studies with more sample size are needed.

Introduction: 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. Methods: 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. Results: 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). Conclusions: 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.

Background: 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. Methods: 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. Results: 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. Conclusions: We report novel lipid species that are associated with MBD in premenopausal women. Studies are needed to validate our results and the translational potential. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusion: It seems metformin and aspirin intakes are associated with MBD. However, further studies with more sample size are needed. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to select parameters from a combined analysis of breast compression, breast morphometry and volumetric breast density, telling about the overall quality of breast positioning, and to apply these investigations on a Moroccan population at the start of new breast cancer screening activities. The study found that compression force in mammography varies greatly and has no specific limit. The researchers attempted to find correlations between compression force and mammographic factors to establish a range of values for standardized compression in mammography.Material and Methods: The study was carried out in a university hospital, a candidate screening center, provided with new technology equipment, qualified staff and doctors of different specialties. Image acquisition was procured on a FFDM Siemens Inspiration system for 250 patients in diagnostic mammography and all patients’ information was collected. The data about dose, the compression force and the thickness of the compressed breast were obtained directly from the DICOM header information, applying Volpara Density software.Results: The results show a correlation between compression force and breast density. The volume of breast tissue compared to the total volume of the breast (VBD) decreased with increasing compressed breast thickness (CBT) and age. The mean VBD was 9.3% ± 6%, the compression force was 71±15 N and the CBT was 53±11 mm.Conclusion: The global analysis and comparison of mammographic parameters showed good similarity between Moroccan and the previous studies population. The mammographic techniques can therefore be used to Moroccan screening programs.

Introduction: Mammographic breast density (MBD) is an established breast cancer risk factor, yet the underlying molecular mechanisms remain to be deciphered. Fibroblast growth factor receptor 1 (FGFR1) amplification is associated with breast cancer development and aberrant FGF signaling found in the biological processes related to both high mammographic density and breast cancer microenvironment. The aim of this study was to investigate the FGF/FGFR1 expression in-between paired tumor-adjacent and tumor tissues from the same patient, and its associations with MBD and tumor characteristics. Methods: FGFR1 expression in paired tissues from 426 breast cancer patients participating in the Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA) cohort study was analyzed by immunohistochemistry. FGF ligand expression was obtained from RNA-sequencing data for 327 of the included patients. Results: FGFR1 levels were differently expressed in tumor-adjacent and tumor tissues, with increased FGFR1 levels detected in 58% of the tumors. High FGFR1 expression in tumor tissues was associated with less favorable tumor characteristics; high histological grade (OR=1.86, 95% CI 1.00–3.44), high Ki67 proliferative index (OR=2.18, 95% CI 1.18– 4.02) as well as tumors of Luminal B-like subtype (OR=2.56, 95%CI 1.29–5.06).While no clear association between FGFR1 expression and MBD was found, FGF ligand (FGF1, FGF11, FGF18) expression was positively correlated with MBD. Discussion: Taken together, these findings support a role of the FGF/FGFR1 system in early breast cancer which warrants further investigation in the MBD– breast cancer context. [ABSTRACT FROM AUTHOR]

Tamoxifen prevents recurrence of breast cancer and is suggested for preventive risk‐reducing therapy. Tamoxifen reduces mammographic density, a proxy for therapy response, but little is known about its effects in remodelling normal breast tissue. Our study, a substudy within the double‐blinded dose‐determination trial KARISMA, investigated tamoxifen‐specific changes in breast tissue composition and histological markers in healthy women. We included 83 healthy women randomised to 6 months daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. The groups were combined to "no dose" (0‐1 mg), "low‐dose" (2.5‐5 mg) or "high‐dose" (10‐20 mg) of tamoxifen. Ultrasound‐guided biopsies were collected before and after tamoxifen exposure. In each biopsy, epithelial, stromal and adipose tissues was quantified, and expression of epithelial and stromal Ki67, oestrogen receptor (ER) and progesterone receptor (PR) analysed. Mammographic density using STRATUS was measured at baseline and end‐of‐tamoxifen‐exposure. We found that different doses of tamoxifen reduced mammographic density and glandular‐epithelial area in premenopausal women and associated with reduced epithelium and increased adipose tissue. High‐dose tamoxifen also decreased epithelial ER and PR expressions in premenopausal women. Premenopausal women with the greatest reduction in proliferation also had the greatest epithelial reduction. In postmenopausal women, high‐dose tamoxifen decreased the epithelial area with no measurable density decrease. Tamoxifen at both low and high doses influences breast tissue composition and expression of histological markers in the normal breast. Our findings connect epithelial proliferation with tissue remodelling in premenopausal women and provide novel insights to understanding biological mechanisms of primary prevention with tamoxifen. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

IntroductionMammographic breast density (MBD) is an established breast cancer risk factor, yet the underlying molecular mechanisms remain to be deciphered. Fibroblast growth factor receptor 1 (FGFR1) amplification is associated with breast cancer development and aberrant FGF signaling found in the biological processes related to both high mammographic density and breast cancer microenvironment. The aim of this study was to investigate the FGF/FGFR1 expression in-between paired tumor-adjacent and tumor tissues from the same patient, and its associations with MBD and tumor characteristics.MethodsFGFR1 expression in paired tissues from 426 breast cancer patients participating in the Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA) cohort study was analyzed by immunohistochemistry. FGF ligand expression was obtained from RNA-sequencing data for 327 of the included patients.ResultsFGFR1 levels were differently expressed in tumor-adjacent and tumor tissues, with increased FGFR1 levels detected in 58% of the tumors. High FGFR1 expression in tumor tissues was associated with less favorable tumor characteristics; high histological grade (OR=1.86, 95% CI 1.00–3.44), high Ki67 proliferative index (OR=2.18, 95% CI 1.18–4.02) as well as tumors of Luminal B-like subtype (OR=2.56, 95%CI 1.29–5.06). While no clear association between FGFR1 expression and MBD was found, FGF ligand (FGF1, FGF11, FGF18) expression was positively correlated with MBD.DiscussionTaken together, these findings support a role of the FGF/FGFR1 system in early breast cancer which warrants further investigation in the MBD–breast cancer context.

Background: Breast cancer (BC) is the most common and deadliest malignancy among women. High mammographic breast density (MBD) is an established modifiable risk marker for BC, and it is of interest, for prevention purposes, to consider lifestyle factors that may modulate both MBD and BC risk. Here, we conducted a systematic review of the most up-to-date evidence on the association between diet as a whole and MBD. Methods: We considered as eligible for inclusion in our review (PROSPERO registration code CRD42022335289) the studies published until 31 December 2021, that reported on the association between a priori or a posteriori dietary patterns (in observational studies) or dietary interventions (in randomized controlled trials) and MBD. Results: In total, twelve studies were included. MBD tended to be inversely associated with adherence to dietary patterns characterized by high consumption of plant-based foods and low in meat, animal fats, and alcohol, defined both a priori (e.g., Mediterranean diet and WCRF/AICR guidelines) or a posteriori (e.g., "fruit-vegetable-cereal" and "salad-sauce-pasta/grains" patterns). Findings from intervention studies were in fair agreement with those from observational studies. Conclusions: While further studies are needed, we found suggestive evidence that the adoption of a healthy diet is associated with lower MBD. [ABSTRACT FROM AUTHOR]

Abstract Background Hormones 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. Methods We 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. Results One 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. Conclusion These 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.

Abstract Background There are no studies done to evaluate the distribution of mammographic breast density and factors associated with it among Pakistani women. Methods Participants included 477 women, who had received either diagnostic or screening mammography at two hospitals in Karachi Pakistan. Mammographic breast density was assessed using the Breast Imaging Reporting and Data System. In person interviews were conducted using a detailed questionnaire, to assess risk factors of interest, and venous blood was collected to measure serum vitamin D level at the end of the interview. To determine the association of potential factors with mammographic breast density, multivariable polytomous logistic regression was used. Results High-density mammographic breast density (heterogeneously and dense categories) was high and found in 62.4% of women. There was a significant association of both heterogeneously dense and dense breasts with women of a younger age group < 45 years (OR 2.68, 95% CI 1.60–4.49) and (OR 4.83, 95% CI 2.54–9.16) respectively. Women with heterogeneously dense and dense breasts versus fatty and fibroglandular breasts had a higher history of benign breast disease (OR 1.90, 95% CI 1.14–3.17) and (OR 3.61, 95% CI 1.90–6.86) respectively. There was an inverse relationship between breast density and body mass index. Women with dense breasts and heterogeneously dense breasts had lower body mass index (OR 0.94 95% CI 0.90–0.99) and (OR 0.81, 95% CI 0.76–0.87) respectively. There was no association of mammographic breast density with serum vitamin D levels, diet, and breast cancer. Conclusions The findings of a positive association of higher mammographic density with younger age and benign breast disease and a negative association between body mass index and breast density are important findings that need to be considered in developing screening guidelines for the Pakistani population.

BackgroundEarly life social environment may influence breast cancer through shaping risk factors operating in early life, adolescence and adulthood, or may be associated with breast cancer risk independent of known risk factors. We investigated the associations between early life socioeconomic status (SES) and mammographic density, a strong risk factor for breast cancer, and the extent to which these associations were independent of risk factors across the lifecourse.MethodsWe used data from an adult follow-up study of two U.S. birth cohorts of women (average age = 43 years) with prospectively collected data starting during the pregnancy of the mother and continuing through early childhood of the offspring. We collected data on factors in later life periods through computer-assisted interviews with the offspring as adults, and obtained routine clinical mammograms for measurement of percent density and dense and nondense breast areas using a computer assisted method. We used generalized estimating equation models for multivariable analysis to account for correlated data for sibling sets within the study sample (n = 700 composed of 441 individuals and 127 sibling sets).ResultsHighest vs. lowest family income level around the time of birth was associated with smaller dense breast area after adjustment for early life factors (e.g., birthweight, maternal smoking during pregnancy) and risk factors in later life periods, including adult body mass index (BMI) and adult SES (β = -8.2 cm2, 95% confidence interval [CI]: -13.3, -3.2). Highest vs. lowest parental educational attainment was associated with higher percent density in models that adjusted for age at mammogram and adult BMI (e.g., β = 4.8, 95% CI = 0.6, 9.1 for maternal education of college or higher degree vs. less than high school), but the association was attenuated and no longer statistically significant after further adjustment for early life factors. There were no associations between early life SES indicators and non-dense area after adjustment for adult BMI. Neither adult education nor adult income was statistically significantly associated with any measure of mammographic density after adjusting for age and adult BMI.ConclusionsWe did not observe consistent associations between different measures of early life SES and mammographic density in adulthood.

Background: High breast density is an independent risk factor for breast cancer and decreases the sensitivity of mammography. This systematic review synthesizes the international clinical guidelines and the evidence base for screening and supplemental screening recommendations in women with dense breasts., Methods: A systematic search of CINHAL, Embase and Medline databases was performed in August 2023 and grey literature searched in January 2024. Two authors independently assessed study eligibility and quality (Appraisal of Guidelines for Research and Evaluation II instrument)., Results: Of 3,809 articles, 23 guidelines published from 2014 to 2024 were included. The content and quality varied between the guidelines; the average AGREE II total score was 58% (range, 23% to 87%). Most guidelines recommended annual or biennial screening mammography for women over 40 years with dense breasts (n = 16). Other guidelines recommended breast tomosynthesis (DBT, n = 6) or magnetic resonance imaging (MRI, n = 1) as the preferred screening modality. A third of the guidelines (n = 8) did not recommend supplemental screening for women with dense breasts. Of those which recommended supplemental screening (n = 14), ultrasound was the preferred modality (n = 7), with MRI (n = 3), DBT (n = 3) and contrast-enhanced mammography (n = 2) also recommended., Conclusions: Consensus on supplemental screening in women with dense breasts is lacking. The quality of the guidelines is variable, and recommendations are largely based on low-quality evidence. As evidence of the benefits versus harms of supplemental screening in women with dense breasts is evolving, it is imperative to improve the methodological quality of breast cancer screening and supplemental screening guidelines., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Breast cancer is a major health problem in Iran with increasing incidence in the recent years. Breast density is one of the most important risk factors for developing breast cancer. Metabolic syndrome that is defined by the presence of multiple clinical and lab data findings has also been shown to be related with breast cancer.Methods: A sample of 246 cases who referred to Mahdiyeh hospital in Tehran were selected according to the inclusion criteria and a form was prepared including breast density in the screening mammogram done in our center and recent lab tests including FBS, HDL and TG. We also measured the waist circumference, height, weight and blood pressure of all subjects. Data analysis was done through SPSS23 and using fishers exact and ordinal regression tests.Results: The incidence of metabolic syndrome was 44% among the cases in this study. Mean age ± standard deviation (SD) was 48.08 ± 7.6 years. There was a significant association between lower breast densities and ages greater than 50 years (p = 0.0). There was no significant association between metabolic syndrome or its components and breast density among the patients above 50 years of age but in ages lower than 50 years, there was a significant association between increased breast density and lower abdominal circumference (p=0.017), lower triglyceride levels (p=0.02), higher HDL levels (p=0.018), lower FBS levels and lower frequency of metabolic syndrome.Conclusion: There was no significant association between metabolic syndrome or its components and mammographic breast density after adjustment for age and BMI.

Abstract Progesterone is a proliferative hormone in the breast but the associations of genetic variations in progesterone-regulated pathways with mammographic breast density (MD) in premenopausal women and whether these associations are mediated through circulating progesterone are not clearly defined. We, therefore, investigated these associations in 364 premenopausal women with a median age of 44 years. We sequenced 179 progesterone receptor (PGR)-related single nucleotide polymorphisms (SNPs). We measured volumetric percent density (VPD) and non-dense volume (NDV) using Volpara. Linear regression models were fit on circulating progesterone or VPD/NDV separately. We performed mediation analysis to evaluate whether the effect of a SNP on VPD/NDV is mediated through circulating progesterone. All analyses were adjusted for confounders, phase of menstrual cycle and the Benjamini–Hochberg false discovery (FDR) adjusted p-value was applied to correct for multiple testing. In multivariable analyses, only PGR rs657516 had a direct effect on VPD (averaged direct effect estimate = − 0.20, 95%CI = − 0.38 ~ − 0.04, p-value = 0.02) but this was not statistically significant after FDR correction and the effect was not mediated by circulating progesterone (mediation effect averaged across the two genotypes = 0.01, 95%CI = − 0.02 ~ 0.03, p-value = 0.70). Five SNPs (PGR rs11571241, rs11571239, rs1824128, rs11571150, PGRMC1 rs41294894) were associated with circulating progesterone but these were not statistically significant after FDR correction. SNPs in PGR-related genes were not associated with VPD, NDV and circulating progesterone did not mediate the associations, suggesting that the effects, if any, of these SNPs on MD are independent of circulating progesterone.

Purpose: Mammographic density (MD) is one of the strongest risk factors for breast cancer (BC). However, the influence of MD on the BC prognosis is unclear. The objective of this study was therefore to investigate whether percentage MD (PMD) is associated with a difference in disease-free or overall survival in primary BC patients. Methods: A total of 2525 patients with primary, metastasis-free BC were followed up retrospectively for this analysis. For all patients, PMD was evaluated by two readers using a semi-automated method. The association between PMD and prognosis was evaluated using Cox regression models with disease-free survival (DFS) and overall survival (OS) as the outcome, and the following adjustments: age at diagnosis, year of diagnosis, body mass index, tumor stage, grading, lymph node status, hormone receptor and HER2 status. Results: After median observation periods of 9.5 and 10.0 years, no influence of PMD on DFS (p = 0.46, likelihood ratio test (LRT)) or OS (p = 0.22, LRT), respectively, was found. In the initial unadjusted analysis higher PMD was associated with longer DFS and OS. The effect of PMD on DFS and OS disappeared after adjustment for age and was caused by the underlying age effect. Conclusions: Although MD is one of the strongest independent risk factors for BC, in our collective PMD is not associated with disease-free and overall survival in patients with BC.

Abstract Background Mammographic breast density (MBD) and benign breast disease (BBD) are two of the strongest risk factors for breast cancer. Understanding trends in MBD by age and parity in women with BBD is essential to the clinical management and prevention of breast cancer. Methods Using data from the Early Determinants of Mammographic Density (EDMD) study, a prospective follow-up study of women born in 1959–1967, we evaluated MBD in 676 women. We used linear regression with generalized estimating equations to examine associations between self-reported BBD and MBD (percent density, dense area, and non-dense area), assessed through a computer-assisted method. Results A prior BBD diagnosis (median age at diagnosis 32 years) was reported by 18% of our cohort. The median time from BBD diagnosis to first available study mammogram was 9.4 years (range 1.1–27.6 years). Women with BBD had a 3.44% higher percent MBD (standard error (SE) = 1.56, p-value = 0.03) on their first available mammogram than women without BBD. Compared with parous women without BBD, nulliparous women with BBD and women with a BBD diagnosis prior to first birth had 7–8% higher percent MBD (β = 7.25, SE = 2.43, p-value

Background: Hormones 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.Methods: We 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.Results: One 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.Conclusion: These 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. [ABSTRACT FROM AUTHOR]

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Percentage mammographic breast density (MBD) is one of the most notable biomarkers. It is assessed visually with the support of radiologists with the four qualitative Breast Imaging Reporting and Data System (BIRADS) categories. It is demanding for radiologists to differentiate between the two variably allocated BIRADS classes, namely, “BIRADS C and BIRADS D.” Recently, convolution neural networks have been found superior in classification tasks due to their ability to extract local features with shared weight architecture and space invariance characteristics. The proposed study intends to examine an artificial intelligence (AI)-based MBD classifier toward developing a latent computer-assisted tool for radiologists to distinguish the BIRADS class in modern clinical progress. This article proposes a multichannel DenseNet architecture for MBD classification. The proposed architecture consists of four-channel DenseNet transfer learning architecture to extract significant features from a single patient's two a mediolateral oblique (MLO) and two craniocaudal (CC) views of digital mammograms. The performance of the proposed classifier is evaluated using 200 cases consisting of 800 digital mammograms of the different BIRADS density classes with validated density ground truth. The classifier's performance is assessed with quantitative metrics such as precision, responsiveness, specificity, and the area under the curve (AUC). The concluding preliminary outcomes reveal that this intended multichannel model has delivered good performance with an accuracy of 96.67% during training and 90.06% during testing and an average AUC of 0.9625. Obtained results are also validated qualitatively with the help of a radiologist expert in the field of MBD. Proposed architecture achieved state-of-the-art results with a fewer number of images and with less computation power.

To investigate the utility of digital breast tomosynthesis (DBT) in the evaluation of focal breast pain, considering breast density and breast cancer risk. Ninety-one cases of focal breast pain evaluated with DBT and ultrasound (US) from 12/30/2014 to 11/9/2017 with 2-year follow-up were identified. Exclusion criteria were non-focal, axillary, or radiating pain; palpable or skin changes; pregnancy or lactation; and history of ipsilateral cancer, trauma, or infection. Demographic data, Tyrer-Cuzick Score (TCS), medical history, breast density, imaging results, and pathology were recorded. Descriptive statistics were reported. Eighteen percent (16/91) of cases demonstrated findings, all benign. Of these, 6% (1/16) were detected by DBT only, 88% (14/16) by US only, and 6% (1/16) by DBT and US. US resulted in 3 benign biopsies. Ninety-nine percent (75/76) of cases with no findings at the site of pain on US also had no findings on DBT. Ninety-eight percent (89/91) of cases with no cancer detected at the site of pain on US also did not have cancer on DBT. DBT detected 2 incidental cancers not associated with pain. DBT and US agreed that there was no finding at the site of pain in 82% (75/91) of cases. A high degree of agreement between DBT and US was seen when stratified by breast density and TCS. DBT may be appropriate for the evaluation of focal pain. Low breast cancer incidence was observed at the site of focal pain across all mammographic breast densities and breast cancer risks. • Low cancer incidence in focal breast pain across breast cancer risks and densities • Digital breast tomosynthesis and ultrasound showed high agreement in focal breast pain. • Digital breast tomosynthesis was typically normal when ultrasound was normal. • Tomosynthesis detected sonographically occult incidental breast cancers. [ABSTRACT FROM AUTHOR]

Background: There are no studies done to evaluate the distribution of mammographic breast density and factors associated with it among Pakistani women.Methods: Participants included 477 women, who had received either diagnostic or screening mammography at two hospitals in Karachi Pakistan. Mammographic breast density was assessed using the Breast Imaging Reporting and Data System. In person interviews were conducted using a detailed questionnaire, to assess risk factors of interest, and venous blood was collected to measure serum vitamin D level at the end of the interview. To determine the association of potential factors with mammographic breast density, multivariable polytomous logistic regression was used.Results: High-density mammographic breast density (heterogeneously and dense categories) was high and found in 62.4% of women. There was a significant association of both heterogeneously dense and dense breasts with women of a younger age group < 45 years (OR 2.68, 95% CI 1.60-4.49) and (OR 4.83, 95% CI 2.54-9.16) respectively. Women with heterogeneously dense and dense breasts versus fatty and fibroglandular breasts had a higher history of benign breast disease (OR 1.90, 95% CI 1.14-3.17) and (OR 3.61, 95% CI 1.90-6.86) respectively. There was an inverse relationship between breast density and body mass index. Women with dense breasts and heterogeneously dense breasts had lower body mass index (OR 0.94 95% CI 0.90-0.99) and (OR 0.81, 95% CI 0.76-0.87) respectively. There was no association of mammographic breast density with serum vitamin D levels, diet, and breast cancer.Conclusions: The findings of a positive association of higher mammographic density with younger age and benign breast disease and a negative association between body mass index and breast density are important findings that need to be considered in developing screening guidelines for the Pakistani population. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common cancer in women. Asian American women have experienced steadily increasing breast cancer incidence rates over the past several decades. The increased rate might be in part due to acculturation. We tested the hypothesis that higher level of acculturation was associated with higher mammographic breast density (MBD), an indicator of breast cancer risk, in a cohort of 425 premenopausal Chinese immigrant women in Philadelphia. Generalized estimating equations accounted for repeated observations and adjusted for age, type of mammographic image, body mass index, months of breastfeeding, number of live births, age at first birth, and menopausal stage (pre, early peri, late peri, post). Results indicated that acculturation level was not associated with any of the MBD measures. Findings were contrary to our hypothesis and previous, cross-sectional studies. In this study population, reproductive factors had a greater effect on MBD than acculturation-related behaviors in adulthood. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is the most common and deadliest malignancy among women. High mammographic breast density (MBD) is an established modifiable risk marker for BC, and it is of interest, for prevention purposes, to consider lifestyle factors that may modulate both MBD and BC risk. Here, we conducted a systematic review of the most up-to-date evidence on the association between diet as a whole and MBD. Methods: We considered as eligible for inclusion in our review (PROSPERO registration code CRD42022335289) the studies published until 31 December 2021, that reported on the association between a priori or a posteriori dietary patterns (in observational studies) or dietary interventions (in randomized controlled trials) and MBD. Results: In total, twelve studies were included. MBD tended to be inversely associated with adherence to dietary patterns characterized by high consumption of plant-based foods and low in meat, animal fats, and alcohol, defined both a priori (e.g., Mediterranean diet and WCRF/AICR guidelines) or a posteriori (e.g., “fruit-vegetable-cereal” and “salad-sauce-pasta/grains” patterns). Findings from intervention studies were in fair agreement with those from observational studies. Conclusions: While further studies are needed, we found suggestive evidence that the adoption of a healthy diet is associated with lower MBD.

Purpose: 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., Material and Methods: 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., Results: 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)., Conclusions: 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., (© Pol J Radiol 2024.)

Purpose: While increased breast density is a risk factor for breast cancer, the effect of fatty liver disease on breast density is unknown. We investigated whether fatty liver is a risk factor for changes in breast density over ~ 4 years of follow-up in pre- and postmenopausal women. Methods: This study included 74,781 middle-aged Korean women with mammographically determined dense breasts at baseline. Changes in dense breasts were identified by more screening mammograms during follow-up. Hepatic steatosis (HS) was measured using ultrasonography. Flexible parametric proportional hazards models were used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs), and a Weibull accelerated failure time model (AFT) was used to determine the time ratios (TRs) and 95% CIs. Results: During a median follow-up of 4.1 years, 4022 women experienced resolution of the dense breasts. The association between HS and dense breast resolution differed by the menopause status (P for interaction < 0.001). After adjusting for body mass index and other covariates, the aHRs (95% CI) for dense breast resolution comparing HS to non-HS were 0.81 (0.70–0.93) in postmenopausal women, while the association was converse in premenopausal women with the corresponding HRs of 1.30 (1.18–1.43). As an alternative approach, the multivariable-adjusted TR (95% CI) for dense breast survival comparing HS to non-HS were 0.81 (0.75–0.87) and 1.19 (1.06–1.33) in premenopausal and postmenopausal women, respectively. Conclusion: The association between HS and changes in dense breasts differed with the menopause status. HS increased persistent dense breast survival in postmenopausal women but decreased it in premenopausal women. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is a major health problem in Iran with increasing incidence in the recent years. Breast density is one of the most important risk factors for developing breast cancer. Metabolic syndrome that is defined by the presence of multiple clinical and lab data findings has also been shown to be related with breast cancer. Methods: A sample of 246 cases who referred to Mahdiyeh hospital in Tehran were selected according to the inclusion criteria and a form was prepared including breast density in the screening mammogram done in our center and recent lab tests including FBS, HDL and TG. We also measured the waist circumference, height, weight and blood pressure of all subjects. Data analysis was done through SPSS23 and using fishers exact and ordinal regression tests. Results: The incidence of metabolic syndrome was 44% among the cases in this study. Mean age ± standard deviation (SD) was 48.08 ± 7.6 years. There was a significant association between lower breast densities and ages greater than 50 years (p = 0.0). There was no significant association between metabolic syndrome or its components and breast density among the patients above 50 years of age but in ages lower than 50 years, there was a significant association between increased breast density and lower abdominal circumference (p=0.017), lower triglyceride levels (p=0.02), higher HDL levels (p=0.018), lower FBS levels and lower frequency of metabolic syndrome. Conclusion: There was no significant association between metabolic syndrome or its components and mammographic breast density after adjustment for age and BMI. [ABSTRACT FROM AUTHOR]

Mammographic density (MD) is one of the strongest risk factors for breast cancer (BC). However, the influence of MD on the BC prognosis is unclear. The objective of this study was therefore to investigate whether percentage MD (PMD) is associated with a difference in disease-free or overall survival in primary BC patients. A total of 2525 patients with primary, metastasis-free BC were followed up retrospectively for this analysis. For all patients, PMD was evaluated by two readers using a semi-automated method. The association between PMD and prognosis was evaluated using Cox regression models with disease-free survival (DFS) and overall survival (OS) as the outcome, and the following adjustments: age at diagnosis, year of diagnosis, body mass index, tumor stage, grading, lymph node status, hormone receptor and HER2 status. After median observation periods of 9.5 and 10.0 years, no influence of PMD on DFS (p = 0.46, likelihood ratio test (LRT)) or OS (p = 0.22, LRT), respectively, was found. In the initial unadjusted analysis higher PMD was associated with longer DFS and OS. The effect of PMD on DFS and OS disappeared after adjustment for age and was caused by the underlying age effect. Although MD is one of the strongest independent risk factors for BC, in our collective PMD is not associated with disease-free and overall survival in patients with BC. • Mammographic density (MD) is one of the strongest risk factors for breast cancer (BC). • Results from a large BC cohort on the impact of percentage MD (PMD) on prognosis. • No association between PMD with disease-free and overall survival was found. • Risk stratification based on PMD seems not feasible for clinical routine. [ABSTRACT FROM AUTHOR]

Purpose: A dense breast on mammogram is a strong risk factor for breast cancer. Identifying factors that reduce mammographic breast density could thus provide insight into breast cancer prevention. Due to the limited number of studies and conflicting findings, we investigated the associations of medication use (specifically statins, aspirin, and ibuprofen) with mammographic breast density. Methods: We evaluated these associations in 775 women who were recruited during an annual screening mammogram at Washington University School of Medicine, St. Louis. We measured mammographic breast density using Volpara. We used multivariable-adjusted linear regressions to determine the associations of medication use (statins, aspirin, and ibuprofen) with mammographic breast density. Least squared means were generated and back-transformed for easier interpretation. Results: The mean age of study participants was 52.9 years. Statin use in the prior 12 months was not associated with volumetric percent density or dense volume, but was positively associated with non-dense volume. The mean volumetric percent density was 8.6% among statin non-users, 7.2% among women who used statins 1–3 days/week, and 7.3% among women who used statins ≥ 4 days/week (p trend = 0.07). The non-dense volume was 1297.1 cm3 among statin non-users, 1368.7 cm3 among women who used statins 1–3 days/week, and 1408.4 cm3 among those who used statins ≥ 4 days/week (p trend = 0.02). We did not observe statistically significant differences in mammographic breast density by aspirin or ibuprofen use. Conclusion: Statin, aspirin, and ibuprofen use was not associated with volumetric percent density and dense volume, but statin use was positively associated with non-dense volume. Any potential associations of these medications with breast cancer risk are unlikely to be mediated through an effect on volumetric percent density. [ABSTRACT FROM AUTHOR]

Purpose: Mammographic breast density (MBD) is a marker of increased breast cancer (BC) risk, yet much remains to be clarified about the underlying mechanisms. We investigated whether DNA methylation patterns differ between high- vs. low-MBD women who developed BC during an 8.9-year median follow-up in the Florence section of the European Prospective Investigation into Cancer and Nutrition. Methods: We analysed 96 pairs of women with BC arising on high- vs. low-MBD breasts (BI-RADS category III–IV vs. I). DNA methylation was determined on pre-diagnostic blood samples using the Illumina Infinium MethylationEPIC BeadChip assay. The statistical analysis was conducted by performing an epigenome-wide association study (EWAS), by searching differentially methylated regions (DMRs) in gene promoters (followed by functional enrichment and gene annotation analysis); and through a "candidate pathways" approach focusing on pre-defined inflammation-related pathways. Results: In EWAS, no single CpG site was differentially methylated between high- and low-MBD women after correction for multiple testing. A total of 140 DMRs were identified, of which 131 were hyper- and 9 hypo-methylated amongst high-MBD women. These DMRs encompassed an annotation cluster of 35 genes coding for proteins implicated in transcription regulation and DNA binding. The "apoptosis signalling" was the only inflammation-related candidate pathway differentially methylated between high- and low-MBD women. Conclusion: Pre-diagnostic methylation patterns differ between high- vs. low-MBD women who subsequently develop BC, particularly, in genes involved in the regulation of DNA transcription and cell apoptosis. Our study provides novel clues about the mechanisms linking MBD and BC. [ABSTRACT FROM AUTHOR]

Background: Smoking is a public health concern that contributes to non-communicable disease fatalities. Nearly five million Malaysians aged 15 years and above are estimated to be smokers. Quitting smoking is complicated and challenging for most smokers to attempt and succeed. Not everyone enjoys it, but some have decided and/or tried to stop smoking completely. This study aimed at identifying predictors of quit smoking attempts. Methods: The researchers designed a cross-sectional study conducted in Samarahan Division, Sarawak, Malaysia. Data from 777 smokers were collected via face-to-face interview using a validated structured questionnaire. A hierarchical multiple regression analysis was performed to determine the factors associated with quit smoking attempts by IBM SPSS version 22.0. A p-value of =.05 was considered statistically significant. Results: The average age of the smokers was 43.46 years old, with the male to female ratio of 8.96:1. The median age of starting and being regular smoking were 20 and 23 years, respectively. The hierarchical multiple linear regression analysis revealed that motivation (ß=.220, p<.001), intention to quit (ß=.148, p<.001), age at regular smoking (ß=.131, p<.01), gender (ß=.088, p<.01) appeared to be significant predictors of quit smoking attempt. Self-efficacy (ß=-.101, p<.05) had a negative effect on quit smoking. However, nicotine dependency and the age of respondents did not affect smoking cessation. Conclusion: Smoking cessation motivation, intention, and age of regular smokers were associated with quit attempts. Therefore, the aim of a future campaign should be to reinforce motivation, increase the level of intention and self-esteem for successful smoking cessation. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Breast density is associated with an increased risk of developing breast cancer. The present study aims to determine the distribution and interobserver variability of mammographic breast density in patients with invasive breast carcinoma, using the fifth edition of BI-RADS guidelines. It is part of a larger study to ascertain the association between mammographic breast density and breast cancer characteristics. MATERIALS AND METHODS: Two radiologists independently assessed 122 mammograms of patients with histologically confirmed invasive breast carcinoma and assigned the breast density to categories A-D based on the fifth edition of BI-RADS guidelines. The interobserver variability was calculated using the weighted kappa coefficient and the level of agreement was determined using the Landis and Koch guidelines. RESULTS: In this study, 55.7% of patients with invasive breast carcinoma were assigned to category B, followed by category C with 36.1%. Only 4.1% of patients were assigned to categories A and D respectively. There was substantial agreement between the two readers' judgement, k=0.610 (95% CI, 0.523-0.697), p < 0.001 for specific BI-RADS categories. CONCLUSION: Among patients with invasive breast carcinoma, there were more patients with non-dense breasts than dense breasts. Overall, there is a substantial interobserver agreement when radiologists used the fifth edition of the BI-RADS guideline, which is in line with results found in the literature. This suggests that the BI-RADS density classification is an acceptable method and can be reliably used in clinical practice. [ABSTRACT FROM AUTHOR]

Digital mammography acts as a unique screening technology to protect the lives of females against breast cancer for the past few decades. Mammographic breast density is a well-known biomarker and plays a substantial role in breast cancer prediction and treatments. Breast density is calculated based on the opacity of fibro-glandular tissue reflected on digital mammograms concerning the whole area of the breast. The opacity of pectoral muscle and fibro-glandular tissue is similar to each other; hence, the small presence of the pectoral muscle in the breast area can hamper the accuracy of breast density classification. Successful removal of pectoral muscle is challenging due to changes in shape, size, and texture of pectoral muscle in every MLO and LMO views of mammogram. In this article, the depth-first search (DFS) algorithm is proposed to remove artifacts and pectoral muscle from digital mammograms. In the proposed algorithm, image enhancement is performed to improve the pixel quality of the input image. The whole breast as a single connected component is identified from the background region to remove the artifacts and tags. The depth-first search method with and without the heuristic approach is used to delineate the pectoral muscle, and then final suppression is performed on it. This algorithm is tested on 2675 images of the DDSM dataset, which is further divided into four density classes as per BIRADs classification. Segmentation results are calculated individually on each BIRADs density class of the DDSM dataset. Results are validated subjectively by the expert's Radiologist's ground truth with segmentation accuracy and objectively by the Jaccard coefficient and a dice similarity coefficient. This algorithm is found robust on each density class and provides overall segmentation accuracy of 86.18%, a mean value of Jaccard index, and a Dice similarity coefficient of 0.9315 and 0.9548, respectively. The experimental results show that the proposed algorithms applied for pectoral muscle removal follow the ground truth marked by an expert radiologist. The proposed algorithm can be part of the pre-processing unit of breast density measurement and breast cancer detection system used during clinical practice. [ABSTRACT FROM AUTHOR]

Background: The low subject contrast between cancerous and fibroglandular tissue could obscure breast abnormalities. Purpose: To investigate radiologists' performance for detection of breast cancer in low and high mammographic density (MD) when cases are digitally acquired. Material and Methods: A test set of 60 digital mammography cases, of which 20 were cancerous, were examined by 17 radiologists. Mammograms were categorized as low (≤50%) or high (>50%) MD and rated for suspicion of malignancy using the Royal Australian and New Zealand College of Radiology (RANZCR) classification system. Radiologist demographics including cases read per year, age, subspecialty, and years of reporting were recorded. Radiologist performance was analyzed by the following metrics: sensitivity; specificity; area under the receiver operating characteristic (ROC) curve (AUC), location sensitivity, and jackknife free-response ROC (JAFROC) figure of merit (FOM). Results: Comparing high to low MD cases, radiologists showed a significantly higher sensitivity (P=0.015), AUC (P=0.003), location sensitivity (P=0.002), and JAFROC FOM (P=0.001). In high compared to low MD cases, radiologists with <1000 annual reads and radiologists with no mammographic subspecialty had significantly higher AUC, location sensitivity, and JAFROC FOM. Radiologists with ≥1000 annual reads and radiologists with mammography subspecialty demonstrated a significant increase in location sensitivity in high compared to low MD cases. Conclusion: In this experimental situation, radiologists' performance was higher when reading cases with high compared to low MD. Experienced radiologists were able to precisely localize lesions in breasts with higher MD. Further studies in unselected screening materials are needed to verify the results. [ABSTRACT FROM AUTHOR]

PURPOSE: We examined whether obesity and a history of diabetes, hypertension, and elevated cholesterol, individually and in combination, are associated with breast density, a strong risk factor for breast cancer. METHODS: We measured percent density and dense area using a computer-assisted method (n = 191; age range = 40-61 years). We used linear regression models to examine the associations of each metabolic condition and the number of metabolic conditions (zero, one, two, and three or four conditions) with breast density. RESULTS: Among individual metabolic conditions, only high blood cholesterol was inversely associated with percent density (β = -5.4, 95% confidence interval [CI]: -8.5, -2.2) and dense area (β = -6.7, 95% CI = -11.1, -2.4). Having multiple metabolic conditions was also associated with lower breast density, with two conditions and three or four conditions versus zero conditions associated with 6.4% (95% CI: -11.2, -1.6) and 7.4% (95% CI: -12.9, -1.9) reduction in percent density and with 6.5 cm(2) (95% CI: -13.1, -0.1) and 9.5 cm(2) (95% CI: -17.1, -1.9) decrease in dense area. CONCLUSIONS: A history of high blood cholesterol and multiple metabolic conditions were associated with lower relative and absolute measures of breast density. The positive association between metabolic abnormalities and breast cancer risk may be driven by pathways unrelated to mammographic breast density.

Abstract Background Obesity 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. Methods We 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,