Fibroglandular Volume Research Articles

Time-specific impact of trace metals on breast density of adolescent girls in Santiago, Chile.

Whether trace metals modify breast density, the strongest predictor for breast cancer, during critical developmental stages such as puberty remains understudied. Our study prospectively evaluated the association between trace metals at Tanner breast stage B1 (n = 291) and at stages both B1 and B4 (n = 253) and breast density at 2 years post-menarche among Chilean girls from the Growth and Obesity Cohort Study. Dual-energy x-ray absorptiometry assessed the volume of dense breast tissue (absolute fibroglandular volume [FGV]) and percent breast density (%FGV). Urine trace metals included arsenic, barium, cadmium, cobalt, cesium, copper, magnesium, manganese, molybdenum, nickel, lead, antimony, selenium, tin, thallium, vanadium, and zinc. At B1, a doubling of thallium concentration resulted in 13.69 cm3 increase in absolute FGV (β: 13.69, 95% confidence interval [CI]: 2.81, 24.52), while a doubling of lead concentration resulted in a 7.76 cm3 decrease in absolute FGV (β: -7.76, 95%CI: -14.71, -0.73). At B4, a doubling of barium concentration was associated with a 10.06 cm3 increase (β: 10.06, 95% CI: 1.44, 18.60), copper concentration with a 12.29 cm3 increase (β: 12.29, 95% CI: 2.78, 21.56), lead concentration with a 9.86 cm3 increase (β: 9.86, 95% CI: 0.73, 18.98), antimony concentration with a 12.97 cm3 increase (β: 12.97, 95% CI: 1.98, 23.79) and vanadium concentration with a 13.14 cm3 increase in absolute FGV (β: 13.14, 95% CI: 2.73, 23.58). Trace metals may affect pubertal breast density at varying developmental stages with implications for increased susceptibility for breast cancer.

Abstract 776: Change in background contrast enhancement category on abbreviated breast MRI with administration of 6 months of bazedoxifene and conjugated estrogen vs wait list control

Abstract Background MRI background contrast enhancement (BPE) has found to be a marker of breast cancer risk providing information beyond that provided by assessment of breast density. BPE is qualitatively classified into categories that correspond to BPE estimates as minimal, <25% BPE; mild, 25-50% BPE; moderate, 50-75% BPE; and marked, >75% BPE. We divided minimal into minimal and almost none (≤5%). We conducted a feasibility study of change in BPE after 6 months of the selective estrogen receptor modulator bazedoxifene (BZA) 20 mg + conjugated estrogen (CE) 0.45 mg marketed commercially as Duavee™ for relief of hot flashes and prevention of osteoporosis in postmenopausal women. Methods STUDY00145121 started 5-27-2020 with randomization to 6 months of Duavee™ vs waitlist control but was stopped after 11 entrants because participants were unable to receive follow-up breast MRIs due to COVID and Duavee™ became unavailable. STUDY0014761 was opened in early 2022 when a source of BZA was found. Doses of BZA and CE were the same as Duavee™ but given as two pills instead of one. 16 women have been randomized to 6 months of BZA/CE vs a wait list control between 2-14-2022 and 9-19-2023. Inclusion criteria are postmenopausal women ages 45-65 at increased risk for breast cancer, BMI < 36 kg/m2 and having current vasomotor symptoms. Participants had a blood draw, 3D mammogram, and abbreviated breast MRI at baseline and the studies were repeated at 6 months. Volumetric density was assessed by Volpara™ fully automated software. Research evaluation of abbreviated MRI background parenchymal contrast enhancement (BPE) was assessed by 5 categories as almost none, minimal, mild, moderate, and marked. BPE was evaluated by a single radiologist blinded to treatment assignment and compared to the 4-category clinical assessment. Results A total of 27 women have been entered in these studies. Six were not evaluable from STUDY00145121 because of the inability to perform 6-month MRI. Two women on STUDY0014761 are not endpoint evaluable due to early drop out and 3 have not yet completed study. A total of 16 women have completed the 6-month portion of the study and abbreviated MRI, with median age 55 (range 47-62) and median BMI 26 kg/m2 (20-33 kg/m2). At baseline, BPE were 3 almost none, 4 minimal, 8 mild, 1 moderate, and 0 marked. There was little correlation between absolute baseline mammographic fibroglandular volume and baseline BPE. A shift in BPE category using the 5-category assessment was noted in 6/11 women (all but one decreased) randomized to BZA +CE and 2/5 women (both decreased) on waitlist. The one increase and four categorical decreases would not have been detected without expansion of BPE to a 5-category system. Conclusion Using the 5-category classification, abbreviated MRI BPE may have promise as a response biomarker in prevention trials for postmenopausal high-risk women. Citation Format: Carol J. Fabian, Onilisa Winblad, Amy Kreutzjans, Krystal Pittman, Christy Altman, Kandy R. Powers, Mary McCarthy, Lauren Nye, Bruce F. Kimler. Change in background contrast enhancement category on abbreviated breast MRI with administration of 6 months of bazedoxifene and conjugated estrogen vs wait list control [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 776.

Breast composition during and after puberty: the Chilean Growth and Obesity Cohort Study

BackgroundBreast density (BD) is a strong risk factor for breast cancer. Little is known about how BD develops during puberty. Understanding BD trajectories during puberty and its determinants could be crucial for promoting preventive actions against breast cancer (BC) at early ages. The objective of this research is to characterize % fibroglandular volume (%FGV), absolute fibroglandular volume (AFGV), and breast volume (BV) at different breast Tanner stages until 4-year post menarche in a Latino cohort and to assess determinants of high %FGV and AFGV during puberty and in a fully mature breast.MethodsThis is a longitudinal follow-up of 509 girls from low-middle socioeconomic status of the Southeast area of Santiago, recruited at a mean age of 3.5 years. The inclusion criteria were singleton birth born, birthweight between 2500 and 4500 g with no medical or mental disorder. A trained dietitian measured weight and height since 3.5 years old and sexual maturation from 8 years old (breast Tanner stages and age at menarche onset). Using standardized methods, BD was measured using dual-energy X-ray absorptiometry (DXA) in various developmental periods (breast Tanner stage B1 until 4 years after menarche onset).ResultsIn the 509 girls, we collected 1,442 breast DXA scans; the mean age at Tanner B4 was 11.3 years. %FGV increased across breast Tanner stages and peaked 250 days after menarche. AFGV and BV peaked 2 years after menarche onset. Girls in the highest quartiles of %FGV, AFGV, and BV at Tanner B4 and B5 before menarche onset had the highest values thereafter until 4 years after menarche onset. The most important determinants of %FGV and AFGV variability were BMI z-score (R2 = 44%) and time since menarche (R2 = 42%), respectively.ConclusionWe characterize the breast development during puberty, a critical window of susceptibility. Although the onset of menarche is a key milestone for breast development, we observed that girls in the highest quartiles of %FGV and AFGV tracked in that group afterwards. Following these participants in adulthood would be of interest to understand the changes in breast composition during this period and its potential link with BC risk.

Time-specific impact of mono-benzyl phthalate (MBzP) and perfluorooctanoic acid (PFOA) on breast density of a Chilean adolescent Cohort

IntroductionHigh mammographic density is among the strongest and most established predictors for breast cancer risk. Puberty, the period during which breasts undergo exponential mammary growth, is considered one of the critical stages of breast development for environmental exposures. Benzylbutyl phthalate (BBP) and perfluorooctanoic acid (PFOA) are pervasive endocrine disrupting chemicals that may increase hormone-sensitive cancers. Evaluating the potential impact of BBP and PFOA exposure on pubertal breast density is important to our understanding of early-life environmental influences on breast cancer etiology. ObjectiveTo prospectively assess the effect of biomarker concentrations of monobenzyl phthalate (MBzP) and PFOA at specific pubertal window of susceptibility (WOS) on adolescent breast density. MethodThis study included 376 Chilean girls from the Growth and Obesity Cohort Study with data collection at four timepoints: Tanner breast stages 1 (B1) and 4 (B4), 1- year post- menarche (1YPM) and 2-years post-menarche (2YPM). Dual-energy X-ray absorptiometry was used to assess the absolute fibroglandular volume (FGV) and percent breast density (%FGV) at 2YPM. We used concentrations of PFOA in serum and MBzP in urine as an index of exposure to PFOA and BBP, respectively. Parametric G-formula was used to estimate the time-specific effects of MBzP and PFOA on breast density. The models included body fat percentage as a time-varying confounder and age, birthweight, age at menarche, and maternal education as fixed covariates. ResultsA doubling of serum PFOA concentration at B4 resulted in a non-significant increase in absolute FGV (β:11.25, 95% confidence interval (CI): −0.28, 23.49)), while a doubling of PFOA concentration at 1YPM resulted in a decrease in % FGV (β:-4.61, 95% CI: −7.45, −1.78). We observed no associations between urine MBzP and breast density measures. ConclusionIn this cohort of Latina girls, PFOA serum concentrations corresponded to a decrease in % FGV. No effect was observed between MBzP and breast density measures across pubertal WOS.

Abstract 6448: Processed, red, and white meat consumption and breast composition in a prospective cohort study of Chilean girls

Abstract Meat consumption has been associated with risk of breast cancer. However, the association between different types of meat (processed and unprocessed red, and white) intake during childhood and breast density has not been explored. This prospective study included 290 Chilean girls from the Growth and Obesity Cohort Study. Diet was assessed every 6 months with a 24-hour recall. Dual-energy X-ray absorptiometry was used to assess breast density (absolute fibroglandular volume (FGV)) and percent breast density (FGV/total breast volume, %FGV) at Tanner Breast Staging 4 (B4). Multivariable linear regression models were adjusted for total calorie intake, age at B4, sugar sweetened beverage intake, vegetable intake, TV watching after school, highest maternal education level, BMI z-score, and height. Substitution analysis was assessed using white meat in replacement of processed and unprocessed red meat. There was no association between total, processed and unprocessed red, or white meat intake and %FGV and absolute FGV. In the estimated substitution analyses, we observed a slightly lower breast density when processed or unprocessed red meat was replaced with white meat; however, effect estimates were modest and imprecise. For example, substituting 1 serving of unprocessed white meat for 1 serving of processed or unprocessed red meat was associated -4.1 cm3 (95% CI -10.3, 2.2) and -4.5 cm3 (95% CI -10.3, 1.3) lower absolute FGV, respectively. In this cohort of Chilean girls, there was little association between total or specific types of meat intake and breast density. Substitution analysis of different types of meat and average breast density at Tanner stage 4 Beta coefficient Confidence interval P value Absolute FGV (cm3) Substituting 1 serving of unprocessed white meat for 1 serving of unprocessed red meat -4.1 (-10.3, 2.2) 0.21 Substituting 1 serving of unprocessed white meat for 1 serving of processed red meat -4.5 (-10.3, 1.3) 0.13 Percentage FGV (%) Substituting 1 serving of unprocessed white meat for 1 serving of unprocessed red meat -2.5 (-5.9, 0.8) 0.14 Substituting 1 serving of unprocessed white meat for 1 serving of processed red meat -2.8 (-5.8, 0.3) 0.08 Citation Format: Claire E. Kim, Audrey J. Gaskins, Camila Corvalan, Ana Pereira, John Shepherd, Karin B. Michels. Processed, red, and white meat consumption and breast composition in a prospective cohort study of Chilean girls [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6448.

407 Moving from observational studies to a clinical trial: the impact of obesity and surgical weight loss on breast imaging, tissue, and cancer screening experience: the B-BRITE study

OBJECTIVES/GOALS: Obesity is associated with increased incidence of breast cancer (BC), yet is not included in many lifetime-risk calculators. Obesity may impact breast cancer screening sensitivity. Retrospective studies show that bariatric surgery is associated with a lower risk of BC, but the effects of surgical weight loss on breast tissue are poorly understood. METHODS/STUDY POPULATION: We proposed a mixed-methods before and after study design to investigate the effects of surgical weight loss on breast tissue via pre- and post-weight loss breast tissue biopsies and imaging. In addition, we aimed to better understand barriers to BC screening for patients with obesity by conducting qualitative interviews. With institutional review board approval, we have begun recruiting 14 cisgender women who plan to undergo Roux-en-Y gastric bypass or sleeve gastrectomy. Participants must be at least 40 years old, with no prior history of breast biopsies or breast cancer and will undergo comprehensive breast cancer screening including mammography with quantitative density assessment, breast MRI, as well as breast core biopsies. RESULTS/ANTICIPATED RESULTS: We hypothesize that obesity and its associated metabolic changes lead to altered breast stroma, including increased inflammation, and tissue stiffness, with subsequent risk of carcinogenesis. If true, we expect to find obese women will have measurably increased inflammatory markers in their breast tissue, which are reduced after bariatric surgery. We expect that change in mammographic density may correlate with fibroglandular volume change on MRI; there are little data on change in background parenchymal enhancement in the setting of obesity and weight change and quantifying this will provide preliminary data for future work. Last, we expect that undergoing BC screening will be easier for patients after weight loss due to constraints of imaging equipment and potential bias in the screening process. DISCUSSION/SIGNIFICANCE: Screening for BC is paramount to improving outcomes yet people with obesity are screened less with worse outcomes. Studying the effects of weight loss on the breast may improve interpretation of breast imaging in the setting of obesity and identify markers of risk. Understanding barriers to screening may help us develop strategies to improve screening.

Abstract A119: Comparing the variability of two validated, quantitative breast density measures used in a community-based mammography registry across race and ethnicity

Abstract Background: Breast density, an independent predictor of breast cancer risk, can be measured in multiple ways. Area-based measures quantify breast tissue in a 2-dimensional (2D) space, whereas volumetric, 3-dimensional (3D) measures incorporate information on the spatial relationship of dense and non-dense tissues that is not captured by 2D measures. Prior studies have shown that both types of measures vary by race/ethnicity. We compared the consistency of the relationship between validated 2D and 3D breast density measures across racial and ethnic groups. Methods: This study used data from 920 women aged 18+ who received a full-field digital screening mammogram at one of 6 breast imaging facilities in central North Carolina between 2017-2018. Race and ethnicity were abstracted from electronic medical records. Quantitative breast density was measured from mammograms and included (1) Area-based density measured using the Laboratory for Individualized Breast Radiodensity Assessment (LIBRA), an algorithm-based software package that produces 2D estimates of the amount of dense breast tissue and total breast area; and (2) Volumetric density measured using Volpara, which produces 3D estimates of breast fibroglandular tissue volume and total breast volume. Percent density was calculated as the ratio of dense or fibroglandular tissue to total breast area or volume. Spearman correlation coefficients (R) and 95% confidence intervals (CI) were used to quantify associations between 2D and 3D measures. Results: Participants were 33-86 years old (mean=57.9, SD=11.2) and identified as White (73%), Black (19%), Asian (3%), and Other race (6%). 5% identified as Hispanic. Percent density measures were highly correlated, with strong correlations across racial groups (White: R=0.88, 95% CI: 0.86, 0.90; Black: R=0.81, 95% CI: 0.75, 0.85; Asian: R=0.91, 95% CI: 0.81, 0.96; Other: R=0.86, 95% CI: 0.77, 0.92), and ethnic groups (Hispanic: R=0.82, 95% CI: 0.71, 0.90; non-Hispanic: R=0.88, 95% CI: 0.87, 0.90). Correlations between dense area and fibroglandular volume were lower, but were also consistent across racial groups (White: R=0.41, 95% CI: 0.35, 0.47; Black: R=0.42, 95% CI: 0.29, 0.54; Asian: R=0.33, 95% CI: -0.07, 0.64; Other: R=0.55, 95% CI: 0.32, 0.72). The correlation between dense area and fibroglandular volume was slightly stronger among Hispanic vs. non-Hispanic women (R=0.62, 95% CI: 0.41, 0.76 vs. R=0.39, 95% CI: 0.33, 0.44), although confidence intervals for the two estimates overlapped suggesting the difference was not statistically significant. Conclusions: Correlations between 2D and 3D percent density measures were consistent across racial and ethnic groups. These data suggest that use of 2D vs. 3D estimation tools is unlikely to contribute to between-study heterogeneity in racial/ethnic differences for studies of breast density in diverse populations. Generalizability for Asian and Hispanic women may be limited by the low prevalence of these groups in our sample. Studies with greater representation are needed for precise estimates in these groups. Citation Format: Brianna D. Taffe, Louise Henderson, Cherie Kuzmiak, Despina Kontos, Sarah Nyante. Comparing the variability of two validated, quantitative breast density measures used in a community-based mammography registry across race and ethnicity [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A119.

A novel Bayesian adaptive design incorporating both primary and secondary endpoints for randomized IIB chemoprevention study of women at increased risk for breast cancer

BackgroundOur randomized controlled clinical trial will explore the potential of bazedoxifene plus conjugated estrogen to modulate breast tissue-based risk biomarkers as a surrogate for breast cancer risk reduction. This paper investigates the statistical design features of the trial and the rationale for the final choice of its design. Group sequential designs are a popular design approach to allow a trial to stop early for success or futility, potentially saving time and money over a fixed trial design. While Bayesian adaptive designs enjoy the same properties as group sequential designs, they have the added benefit of using prior information as well as inferential interpretation conditional on the data. Whether a frequentist or Bayesian trial, most adaptive designs have interim analyses that allow for early stopping, typically utilizing only the primary endpoint. A drawback to this approach is that the study may not have enough data for adequate comparisons of a single, key secondary endpoint. This can happen, for example, if the secondary endpoint has a smaller effect than the primary endpoint.MethodsIn this paper, we investigate a trial design called two-endpoint adaptive, which stops early only if a criterion is met for primary and secondary endpoints. The approach focuses the final analysis on the primary endpoint but ensures adequate data for the secondary analysis. Our study has two arms with a primary (change in mammographic fibroglandular volume) and secondary endpoint (change in mammary tissue Ki-67).ResultsWe present operating characteristics including power, trial duration, and type I error rate and discuss the value and risks of modeling Bayesian group sequential designs with primary and secondary endpoints, comparing against alternative designs. The results indicate that the two-endpoint adaptive design has better operating characteristics than competing designs if one is concerned about having adequate information for a key secondary endpoint.DiscussionOur approach balances trial speed and the need for information on the single, key secondary endpoint.

Variability in urinary phthalates, phenols, and parabens across childhood and relation to adolescent breast composition in Chilean girls

BackgroundEpidemiologic evidence suggests that environmental factors acting as endocrine disrupting chemicals (EDCs) are associated with mammographic breast density and the risk of breast cancer. Exposure to EDCs during puberty, a period of rapid breast development, may affect susceptibility to breast carcinogenesis. MethodsIn a cohort of 366 Chilean adolescents from the Growth and Obesity Cohort Study, we evaluated the relation between urinary concentrations of 15 suspected EDC biomarkers across three pubertal time points (Tanner breast stage 1 (B1), 4 (B4), and 1-year post-menarche) and breast fibroglandular volume (FGV; percent FGV [%FGV] and absolute FGV [aFGV]) and total breast volume (tBV) at 2-years post-menarche. We used linear mixed models to test differences in creatinine-corrected EDC biomarker concentrations at B4 and 1-year post-menarche compared to B1 and calculated intraclass correlation coefficients (ICC) of EDC concentrations across time points to appraise the consistency of measurements. We fit multivariable generalized estimating equations (GEEs) to evaluate windows of susceptibility for the association between log10-transformed EDCs and log10-transformed breast outcomes. GEEs were adjusted for age, body fat percentage, total caloric intake, and maternal education. ResultsUrinary EDC biomarker concentrations highly varied across pubertal time points (ICC range 0.01–0.30). For 12 EDCs, biomarker concentrations decreased over time. Triclosan measured at 1-year post-menarche was inversely associated with %FGV at 2-years post-menarche (β = −0.025, 95 % confidence interval = −0.041, −0.008). Mono(2-ethyl-5-carboxypentyl) phthalate and the sum of di(2-ethylhexyl) phthalate metabolite concentrations at B4 were positively associated with aFGV and tBV at 2-years post-menarche. No measured phenols were associated with aFGV and tBV, while no measured parabens were associated with %FGV and aFGV. ConclusionsOur study suggests relatively high variability in EDC biomarker concentrations across the peripubertal time period. We also found evidence to suggest that there may be pubertal windows of susceptibility to select EDCs for the association with adolescent breast density.

A comparison of various methods for measuring breast density and breast tissue composition in adolescent girls and women

This study compared different approaches to measuring breast density and breast tissue composition (BTC) in adolescent girls (n = 42, aged 14–16 years) and their mothers (n = 39, aged 36–61 years) from a cohort in Santiago, Chile. Optical spectroscopy (OS) was used to measure collagen, water, and lipid concentrations, which were combined into a percent breast density index (%BDI). A clinical dual-energy X-ray absorptiometry (DXA) system calibrated to measure breast density provided percent fibroglandular volume (%FGV) from manually delineated images. After digitizing mammogram films, the percent mammographic breast density (%MBD) was measured using computer-assisted software. Partial correlation coefficients (rpartial) were used to evaluate associations between breast density measures and BTC from these three different measurement approaches, adjusting for age and body mass index. %BDI from OS was associated with %FGV from DXA in adolescent girls (rpartial = 0.46, p-value = 0.003), but not in mothers (rpartial = 0.17, p-value = 0.32). In mothers, %FGV from DXA was associated with %MBD from mammograms (rpartial = 0.60, p-value < 0.001). These findings suggest that data from OS, DXA, and mammograms provide related but distinct information about breast density and BTC. Future studies should explore how the information provided by these different devices can be used for breast cancer risk prediction in cohorts of adolescent girls and women.

Prediction of breast cancer risk by automated volumetric breast density measurement.

Dense breast (DB) is recognized as a breast cancer (BC) risk factor. Although DB is common in Japanese women, the incidence of BC is lower than in Caucasians. We evaluated whether DB is a risk factor or whether there are other risk factors for BC in Japanese women. We retrospectively analyzed 635 BC patients and 999 controls who received a mammography at our hospital between February 2019 and March 2021. Volumetric breast density percentage (VBD%), breast volume (BV), and fibroglandular volume (FGV) were measured using Volpara™, an automated, three-dimensional image analysis program. A VBD% of 7.5% or higher was classified as DB. The association between the VBD%, BV, and FGV, and BC risk were assessed using logistic regression. Of the BC group and the control group, 77% and 79% had DB. The stratified FGV was positively associated with BC risk (odds ratio: 2.84; 95% confidence interval 1.58-5.12; P < 0.001). No significant association was found between either the VBD% or BV and BC risk. The proportion of Japanese women with DB was high, suggesting that DB might not be significantly associated with BC risk. However, our results also suggested that the FGV may be related to BC risk in Japanese women.

Habitual Phytoestrogen Intake Is Associated with Breast Composition in Girls at 2 Years after Menarche Onset.

High phytoestrogen intake during adolescence is associated with a reduced risk of breast cancer. Breast density (BD) is a strong predictor of breast cancer and can be considered an early marker. We aim to assess the association between the mean habitual intake of isoflavones, lignans, and total phytoestrogens intake during puberty until 2 years after menarche onset and absolute fibroglandular volume (AFGV) and percentage of fibroglandular volume (%FGV) in Hispanic girls at the end of puberty. Longitudinal study set up in the Growth and Obesity Chilean Cohort Study (GOCS). We included 329 girls with dietary data (multiple 24-hours recalls) from puberty until 2 years after menarche onset (81% had 2-4 recalls). Two international datasets were used to estimate isoflavones, lignans, and total phytoestrogens in the diet. Breast composition was measured by dual energy X-ray absorptiometry at 2 years after menarche. Multiple linear regression models were used to assess the association between isoflavones, lignans, and total phytoestrogens intake and AFGV and %FGV. The average total phytoestrogen intake was 1 mg/day and %FGV was 50.7% (SD = 15.2) and AFGV 218.8 cm3 (SD = 79.3). An inverse association was found between consumption of isoflavones and AFGV, as well as, with total phytoestrogens [Q4 vs. Q1 adjusted model ß = -49.2 cm3; 95% CI (-85.5 to -13.0)]. Girls with a higher intake of total phytoestrogens and isoflavones during puberty until 2 years after menarche onset had significantly lower AFGV. Although the intake of phytoestrogens is low in Western populations, higher consumption of them during a critical period of life like puberty could be beneficial to reduce breast cancer during adulthood.

Sugar-sweetened beverage consumption and breast composition in a longitudinal study of Chilean girls

BackgroundFrequent sugar-sweetened beverage (SSB) intake has been associated with indirect markers of breast cancer risk, such as weight gain in adolescents and early menarche. How SSB intake relates to breast composition in adolescent girls has not been explored.MethodsWe evaluated the association between prospective intake of SSB and breast density in a cohort of 374 adolescent girls participating in the Growth and Obesity Cohort Study in Santiago, Chile. Multivariable linear regression models were used to analyze the association between average daily SSB intake quartiles and breast composition (absolute fibroglandular volume [aFGV], percent fibroglandular volume [%FGV], total breast volume [tBV]). Models were adjusted for potential confounding by BMI Z-score, age, daily energy intake (g/day), maternal education, hours of daily television watching after school, dairy intake (g/day), meat intake (g/day), waist circumference, and menarche. To examine the sensitivity of the association to the number of dietary recalls for each girl, analyses were further stratified by girls with one dietary recall and girls with > one dietary recall.ResultsA total of 881 dietary recalls were available for 374 girls prior to the breast density assessment. More than 60% of the cohort had > one dietary recall available. In multivariable analyses, we found no association between SSB intake quartile and aFGV (Q2 vs Q1 β: − 5.4, 95% CI − 15.1, 4.4; Q3 vs Q1 β: 1.3, 95% CI − 8.6, 11.3; Q4 vs Q1 β: 3.0, 95% CI − 7.1, 13). No associations were noted for %FGV and tBV. Among girls with at least one dietary recall, we found no significant associations between SSB intake quartiles and %FGV, aFGV, or tBV.ConclusionOverall, we observed no evidence that SSB intake was associated with breast density in adolescent Chilean girls.

The Association Between Breast Density and Gut Microbiota Composition at 2 Years Post-Menarche: A Cross-Sectional Study of Adolescents in Santiago, Chile.

The gut microbiome has been linked to breast cancer via immune, inflammatory, and hormonal mechanisms. We examined the relation between adolescent breast density and gut microbial composition and function in a cohort of Chilean girls. This cross-sectional study included 218 female participants in the Growth and Obesity Cohort Study who were 2 years post-menarche. We measured absolute breast fibroglandular volume (aFGV) and derived percent FGV (%FGV) using dual energy X-ray absorptiometry. All participants provided a fecal sample. The gut microbiome was characterized using 16S ribosomal RNA sequencing of the V3-V4 hypervariable region. We examined alpha diversity and beta diversity across terciles of %FGV and aFGV. We used MaAsLin2 for multivariable general linear modeling to assess differential taxa and predicted metabolic pathway abundance (MetaCyc) between %FGV and aFGV terciles. All models were adjusted for potential confounding variables and corrected for multiple comparisons. The mean %FGV and aFGV was 49.5% and 217.0 cm3, respectively, among study participants. Similar median alpha diversity levels were found across %FGV and aFGV terciles when measured by the Shannon diversity index (%FGV T1: 4.0, T2: 3.9, T3: 4.1; aFGV T1: 4.0, T2: 4.0, T3: 4.1). %FGV was associated with differences in beta diversity (R2 = 0.012, p=0.02). No genera were differentially abundant when comparing %FGV nor aFGV terciles after adjusting for potential confounders (q > 0.56 for all genera). We found no associations between predicted MetaCyc pathway abundance and %FGV and aFGV. Overall, breast density measured at 2 years post-menarche was not associated with composition and predicted function of the gut microbiome among adolescent Chilean girls.

The Potential Role of the Fat-Glandular Interface (FGI) in Breast Carcinogenesis: Results from an Ultrasound Tomography (UST) Study.

This study explored the relationship between the extent of the fat–glandular interface (FGI) and the presence of malignant vs. benign lesions. Two hundred and eight patients were scanned with ultrasound tomography (UST) as part of a Health Insurance Portability and Accountability Act (HIPAA)-compliant study. Segmentation of the sound speed images, employing the k-means clustering method, was used to help define the extent of the FGI for each patient. The metric, α, was defined as the surface area to volume ratio of the segmented fibroglandular volume and its mean value across patients was determined for cancers, fibroadenomas and cysts. ANOVA tests were used to assess significance. The means and standard deviations of α for cancers, fibroadenomas and cysts were found to be 4.0 ± 2.0 cm−1, 3.1 ± 1.7 cm−1 and 2.3 ± 0.9 cm−1, respectively. The differences were statistically significant (p < 0.001). The separation between the groups increased when α was measured on only the image slice where the finding was most prominent, with values for cancers, fibroadenomas and cysts of 5.4 ± 3.6 cm−1, 3.6 ± 2.3 cm−1 and 2.4 ± 1.5 cm−1, respectively. Of the three types of masses studied, cancer was associated with the most extensive FGIs, suggesting a potential role for the FGI in carcinogenesis, a subject for future studies.

Automated Breast Density Measurement in Mammography for Cancer Risk Stratification

HomeRadiology: Imaging CancerVol. 3, No. 6 PreviousNext Research HighlightsFree AccessAutomated Breast Density Measurement in Mammography for Cancer Risk StratificationSurrin DeenSurrin DeenSurrin DeenPublished Online:Nov 26 2021https://doi.org/10.1148/rycan.2021219025MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In Take-Away Points■ Major Focus: Breast density (BD) was quantified using automated software and compared with subjective radiologist rating of BD.■ Key Result: Automated software improved discrimination of cancer type and of interval cancers compared with visual assessment by a radiologist.■ Impact: Automated BD measurements from mammograms have the potential to stratify patients undergoing breast cancer screening, reducing false-positive rates and the frequency of unnecessary further tests such as MRI or biopsy.Stratified or risk-based breast cancer screening aims to select the most suitable personalized screening regimen for individual patients by estimating the likelihood of developing cancer and balancing this against the negative impact of unnecessary tests. Risk-based stratification algorithms incorporate BD classified subjectively by a radiologist in Breast Imaging Reporting and Data System.In the retrospective case-control study highlighted here, the authors used a U.K.-based population database, the OPTIMAM Database, to identify screening mammograms with cancer in women aged 47EN_DASH73 years. Cancer-free controls (n = 605) were identified and matched to cancer cases (n = 599) on the basis of age and the imaging equipment used. Automated software (Volpara, version 1.5.1; Volpara Health Technologies) calculated fibroglandular volume (FGV), volumetric BD (VBD), and density grade (DG). This was compared to BD assessed by a blinded radiologist using a visual analogue scale (VAS) from 0 to 100.The relative discriminative ability of FGV, both overall and for individual cancer subtypes, was found to be either equivalent to or greater than that of VAS or VBD, whether using statistical analyses based on logistic regression, receiver operating characteristic curves, or number of cancers included in the highest risk category (highest quartile). FGV provided the steepest risk gradient for all cancers, with an odds ratio (OR) for the highest quartile compared to the lowest quartile of 3.7 (95% CI: 2.5, 5.6). FGV quartile, VBD quartile, and DG also predicted node-positive cancers, and FGV quartile demonstrated the steepest risk gradient for interval (OR, 5.3; CI: 3.1, 9.1; P < .01), node-positive (OR, 4.7; CI: 2.5, 9.0; P < .01), and combined cancers (OR, 4.7; CI: 2.9, 7.8; P < .01).This study suggests that automated FGV may provide a good foundation for stratified breast cancer screening. However, information on several covariates was not collected in this study, necessitating further work to confirm this finding.Highlighted ArticleBurnside ES, Warren LM, Myles J, et al. Quantitative breast density analysis to predict interval and node-positive cancers in pursuit of improved screening protocols: a case-control study. Br J Cancer 2021;125(6):884–892. doi: https://doi.org/10.1038/s41416-021-01466-yHighlighted ArticleBurnside ES, Warren LM, Myles J, et al. Quantitative breast density analysis to predict interval and node-positive cancers in pursuit of improved screening protocols: a case-control study. Br J Cancer 2021;125(6):884–892. doi: https://doi.org/10.1038/s41416-021-01466-y Crossref, Medline, Google ScholarArticle HistoryPublished online: Nov 26 2021 FiguresReferencesRelatedDetailsRecommended Articles Impact of New Technology Adoption on Breast Cancer ScreeningRadiology2018Volume: 290Issue: 3pp. 638-639Age-based versus Risk-based Mammography Screening in Women 40–49 Years Old: A Cross-sectional StudyRadiology2019Volume: 292Issue: 2pp. 321-328MRI Screening Interval in Women with a History of Breast CancerRadiology2021Volume: 300Issue: 2pp. 312-313Fully Automated Volumetric Breast Density Estimation from Digital Breast TomosynthesisRadiology2021Volume: 301Issue: 3pp. 561-568Deep Learning Predicts Interval and Screening-detected Cancer from Screening Mammograms: A Case-Case-Control Study in 6369 WomenRadiology2021Volume: 301Issue: 3pp. 550-558See More RSNA Education Exhibits Let’s Talk about Next-Generation Breast Cancer Screening Programs: How Should We Do? What Should We Use?Digital Posters2020The Impact of New Genetic Mutations Associated with Breast Cancer on Breast MRI ScreeningDigital Posters2020Dense Breast: Is It Really Looking for a Needle in the Haystack? Digital Posters2020 RSNA Case Collection Malignancy on abbreviated screening breast MRIRSNA Case Collection2020Multifocal breast cancerRSNA Case Collection2020Breast density change with hormone replacement RSNA Case Collection2021 Vol. 3, No. 6 Metrics Altmetric Score PDF download

Abstract 2567: Duavee® improves metabolic health without increasing cancer risk: findings from a preclinical model of obesity and postmenopausal breast cancer

Abstract Introduction: Many women at high risk for breast cancer will not take standard selective estrogen receptor modulators (SERMs) for cancer prevention due to concern of side effects, especially vasomotor symptoms. Duavee®, a tissue selective complex of the SERM bazedoxifene (BZA; 20mg) + conjugated estrogen (CE; 0.45mg), is FDA approved for relief of hot-flashes. Preclinical and early phase human studies suggest Duavee® has potential for breast cancer prevention, with favorable change in mammographic fibroglandular volume and proliferation. Given the &amp;gt;40% incidence of obesity in postmenopausal women, and that obesity increases breast cancer risk, the current study was aimed at identifying the effects of obesity on response to Duavee® in a rodent model of obesity and postmenopausal breast cancer. Methods: This study used our well-characterized rat model of diet-induced obesity and postmenopausal ER-positive breast cancer. Rats were injected with N-methylnitrosourea (MNU, 50 mg/kg) at 7 weeks of age to induce mammary tumors and fed a high fat diet (HF; 46% kcal fat) to promote obesity. Lean and obese rat were selected based on % body fat at 16 weeks. Tumors were monitored by manual palpation weekly and measured using digital calipers. Tumor-bearing rats were ovariectomized (OVX) when a tumor reached 0.7cm3. Rats were then maintained on ad libitum HF diet or HF diet plus a daily oral dose of Duavee® (3mg BZA+ 0.07mg CE/kg body weight) for 8 weeks. Body composition was analyzed biweekly (qMR) and fat pads weighed at study end to determine regional fat distribution. Results: Like menopause in women, OVX induces weight gain in this model. Duavee® significantly blunted the OVX-induced weight gain in both lean (-65%, p&amp;lt;0.001) and obese (-88%, p&amp;lt;0.001) rats compared to controls. Similarly, Duavee®-treated rats gained less body fat after OVX vs controls (-50% lean; -97% obese, p&amp;lt;0.001). Duavee® administration was associated with reduction in glucose in obese rats after 2 weeks and in lean and obese rats after 8 weeks (-11% vs controls, p=0.03). The effects of Duavee® on regional fat deposition varied by adiposity. Obese Duavee®-treated rats had significantly lower pericardial fat (-17%, p&amp;lt;0.05) and tended to have lower mammary fat (-19%, p=0.08); lean rats had less gonadal fat (-20%, p&amp;lt;0.05), while deposition in this region was not altered by Duavee® in obese rats. At 8 weeks there was no evidence that Duavee® promoted tumor development or growth in lean or obese OVX rats. Conclusions: These data suggest that Duavee® may provide beneficial effects on body composition and metabolism in obese OVX animals without promotion of tumor growth. Further analyses will include study of direct effects of Duavee® on tumors, the tumor microenvironment, and systemic markers of insulin resistance and mammary cancer risk in our rat model of pre-and postmenopausal obesity and breast cancer. Citation Format: Karen A. Corleto, Tara N. Mahmood, Danilo Landrock, Stephen D. Hursting, Carol J. Fabian, Bruce F. Kimler, Erin D. Giles. Duavee® improves metabolic health without increasing cancer risk: findings from a preclinical model of obesity and postmenopausal breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2567.

Quantitative breast density analysis to predict interval and node-positive cancers in pursuit of improved screening protocols: a case\u2013control study

BackgroundThis study investigates whether quantitative breast density (BD) serves as an imaging biomarker for more intensive breast cancer screening by predicting interval, and node-positive cancers.MethodsThis case–control study of 1204 women aged 47–73 includes 599 cancer cases (302 screen-detected, 297 interval; 239 node-positive, 360 node-negative) and 605 controls. Automated BD software calculated fibroglandular volume (FGV), volumetric breast density (VBD) and density grade (DG). A radiologist assessed BD using a visual analogue scale (VAS) from 0 to 100. Logistic regression and area under the receiver operating characteristic curves (AUC) determined whether BD could predict mode of detection (screen-detected or interval); node-negative cancers; node-positive cancers, and all cancers vs. controls.ResultsFGV, VBD, VAS, and DG all discriminated interval cancers (all p < 0.01) from controls. Only FGV-quartile discriminated screen-detected cancers (p < 0.01). Based on AUC, FGV discriminated all cancer types better than VBD or VAS. FGV showed a significantly greater discrimination of interval cancers, AUC = 0.65, than of screen-detected cancers, AUC = 0.61 (p < 0.01) as did VBD (0.63 and 0.53, respectively, p < 0.001).ConclusionFGV, VBD, VAS and DG discriminate interval cancers from controls, reflecting some masking risk. Only FGV discriminates screen-detected cancers perhaps adding a unique component of breast cancer risk.

Digital breast tomosynthesis in a population based mammographic screening program: Breast compression and early performance measures

PurposeWe aimed to determine if compression force or pressure could be associated with early performance measures for women screened with digital breast tomosynthesis (DBT) in BreastScreen Norway. Early performance measures included rates of consensus, recall, and screen-detected breast cancer. MethodData on compression force and pressure, compressed breast thickness and breast characteristics were extracted from an automated software for density assessment of DBT screening examinations for 25,286 women. For descriptive analyses, force (Newton, N) and pressure (kilopascal, kPa) were categorized into quartiles. Analyses were stratified by mammographic view, craniocaudal (CC) and mediolateral oblique (MLO). Logistic regression with restricted cubic splines was used to investigate the association between force and pressure as continuous exposures and early performance measures adjusted for age, compressed breast thickness and fibroglandular volume. ResultsMean age of the screened women was 60.7 (SD = 5.2) years. Mean compression force was 90.8 (SD = 14.2) N for CC and 106.3 (SD = 20.6) N for MLO, and pressure was 11.3 (SD = 3.6) kPa for CC and 8.7 (SD = 2.0) kPa for MLO. The highest rates of screen-detected cancer were observed for low force (1.04 % for <82.5 N for CC and 1.07 % for <92.0 N for MLO) and low pressure (1.07 % for <7.2 kPa for MLO). No association was found between force or pressure as continuous exposures and early performance measures in adjusted regression analyses. ConclusionsWe found the highest rates of screen-detected cancer for low force and pressure, but no significant association between continuous values of force or pressure and early performance measures in DBT. The findings might indicate that the levels of force and pressure in DBT are of lower significance for screening performance than reported in standard digital mammography.

Association between indicators of systemic inflammation biomarkers during puberty with breast density and onset of menarche

BackgroundSystemic inflammation may play a role in shaping breast composition, one of the strongest risk factors for breast cancer. Pubertal development presents a critical window of breast tissue susceptibility to exogenous and endogenous factors, including pro-inflammatory markers. However, little is known about the role of systemic inflammation on adolescent breast composition and pubertal development among girls.MethodsWe investigated associations between circulating levels of inflammatory markers (e.g., interleukin-6 (IL-6), tumor necrosis factor receptor 2 (TNFR2), and C-reactive protein (CRP)) at Tanner stages 2 and 4 and breast composition at Tanner stage 4 in a cohort of 397 adolescent girls in Santiago, Chile (Growth and Obesity Cohort Study, 2006–2018). Multivariable linear models were used to examine the association between breast composition and each inflammatory marker, stratifying by Tanner stage at inflammatory marker measurement. Accelerated failure time models were used to evaluate the association between inflammatory markers concentrations at each Tanner stage and time to menarche.ResultsIn age-adjusted linear regression models, a doubling of TNFR2 at Tanner 2 was associated with a 26% (95% CI 7–48%) increase in total breast volume at Tanner 4 and a 22% (95% CI 10–32%) decrease of fibroglandular volume at Tanner 4. In multivariable models further adjusted for body fatness and other covariates, these associations were attenuated to the null. The time to menarche was 3% (95% CI 1–5%) shorter among those in the highest quartile of IL-6 at Tanner 2 relative to those in the lowest quartile in fully adjusted models. Compared to those in the lowest quartile of CRP at Tanner 4, those in the highest quartile experienced 2% (95% CI 0–3%) longer time to menarche in multivariable models.ConclusionsSystemic inflammation during puberty was not associated with breast volume or breast density at the conclusion of breast development among pubertal girls after adjusting for body fatness; however, these circulating inflammation biomarkers, specifically CRP and IL-6, may affect the timing of menarche onset.