Mammographic Density In Premenopausal Women Research Articles

Residential exposure to traffic pollution and mammographic density in premenopausal women

BackgroundMammographic density (MD) is the most important breast cancer biomarker. Ambient pollution is a carcinogen, and its relationship with MD is unclear. This study aims to explore the association between exposure to traffic pollution and MD in premenopausal women. MethodologyThis Spanish cross-sectional study involved 769 women attending gynecological examinations in Madrid. Annual Average Daily Traffic (AADT), extracted from 1944 measurement road points provided by the City Council of Madrid, was weighted by distances (d) between road points and women's addresses to develop a Weighted Traffic Exposure Index (WTEI). Three methods were employed: method-1 (1dAADT), method-2 (1dAADT), and method-3 (e1dAADT). Multiple linear regression models, considering both log-transformed percentage of MD and untransformed MD, were used to estimate MD differences by WTEI quartiles, through two strategies: “exposed (exposure buffers between 50 and 200 m) vs. not exposed (>200 m)”; and “degree of traffic exposure”. ResultsResults showed no association between MD and traffic pollution according to buffers of exposure to the WTEI (first strategy) for the three methods. The highest reductions in MD, although not statistically significant, were detected in the quartile with the highest traffic exposure. For instance, method-3 revealed a suggestive inverse trend (eβQ1 = 1.23, eβQ2 = 0.96, eβQ3 = 0.85, eβQ4 = 0.85, p-trend = 0.099) in the case of 75 m buffer. Similar non-statistically significant trends were observed with Methods-1 and -2. When we examined the effect of traffic exposure considering the all the 1944 measurement road points in every participant (second strategy), results showed no association for any of the three methods. A slightly decreased MD, although not significant, was observed only in the quartile with the highest traffic exposure: eβQ4 = 0.98 (method-1), and eβQ4 = 0.95 (methods-2 and -3). ConclusionsOur results showed no association between exposure to traffic pollution and MD in premenopausal women. Further research is needed to validate these findings.

The association between mammographic density and breast cancer risk in Chinese women: a systematic review and meta-analysis

PurposeBreast density has consistently been shown to be an independent risk factor for breast cancer in Western populations; however, few studies have evaluated this topic in Chinese women and there is not yet a unified view. This study investigated the association between mammographic density (MD) and breast cancer risk in Chinese women.MethodsThe PubMed, Cochrane Library, Embase, and Wanfang databases were systematically searched in June 2023 to include all studies on the association between MD and breast cancer risk in Chinese women. A total of 13,977 breast cancer cases from 14 studies were chosen, including 10 case-control/cross-sectional studies, and 4 case-only studies. For case-control/cross-sectional studies, the odds ratios (ORs) of MD were combined using random effects models, and for case-only studies, relative odds ratios (RORs) were combinations of premenopausal versus postmenopausal breast cancer cases.ResultsWomen with BI-RADS density category II-IV in case-control/cross-sectional studies had a 0.93-fold (95% confidence interval [CI] 0.55, 1.57), 1.08-fold (95% CI 0.40, 2.94), and 1.24-fold (95% CI 0.42, 3.69) higher risk compared to women with the lowest density category. Combined RORs for premenopausal versus postmenopausal women in case-only studies were 3.84 (95% CI 2.92, 5.05), 22.65 (95% CI 7.21, 71.13), and 42.06 (95% CI 4.22, 419.52), respectively, for BI-RADS density category II-IV versus I.ConclusionsFor Chinese women, breast cancer risk is weakly associated with MD; however, breast cancer risk is more strongly correlated with mammographic density in premenopausal women than postmenopausal women. Further research on the factors influencing MD in premenopausal women may provide meaningful insights into breast cancer prevention in China.

Biomarkers of mammographic density in premenopausal women

BackgroundWhile mammographic density is one of the strongest risk factors for breast cancer, little is known about its determinants, especially in young women. We applied targeted metabolomics to identify circulating metabolites specifically associated with mammographic density in premenopausal women. Then, we aimed to identify potential correlates of these biomarkers to guide future research on potential modifiable determinants of mammographic density.MethodsA total of 132 metabolites (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, sphingolipids, hexose) were measured by tandem liquid chromatography/mass spectrometry in plasma samples from 573 premenopausal participants in the Mexican Teachers’ Cohort. Associations between metabolites and percent mammographic density were assessed using linear regression models, adjusting for breast cancer risk factors and accounting for multiple tests. Mean concentrations of metabolites associated with percent mammographic density were estimated across levels of several lifestyle and metabolic factors.ResultsSphingomyelin (SM) C16:1 and phosphatidylcholine (PC) ae C30:2 were inversely associated with percent mammographic density after correction for multiple tests. Linear trends with percent mammographic density were observed for SM C16:1 only in women with body mass index (BMI) below the median (27.4) and for PC ae C30:2 in women with a BMI over the median. SM C16:1 and PC ae C30:2 concentrations were positively associated with cholesterol (total and HDL) and inversely associated with number of metabolic syndrome components.ConclusionsWe identified new biomarkers associated with mammographic density in young women. The association of these biomarkers with mammographic density and metabolic parameters may provide new perspectives to support future preventive actions for breast cancer.

Use of Low-Dose Tamoxifen to Increase Mammographic Screening Sensitivity in Premenopausal Women.

Simple SummaryThis is the first study to model the effects of tamoxifen on mammographic density and screening sensitivity. Low-dose tamoxifen reduces mammographic density in premenopausal women by, on average, 20%. Potential outcome analyses suggest that a reduction in mammographic density improves mammography screening sensitivity, reduces the proportion of large tumors, and subsequent interval cancers.Increased breast density decreases mammographic sensitivity due to masking of cancers by dense tissue. Tamoxifen exposure reduces mammographic density and, therefore, should improve screening sensitivity. We modelled how low-dose tamoxifen exposure could be used to increase mammographic sensitivity. Mammographic sensitivity was calculated using the KARMA prospective screening cohort. Two models were fitted to estimate screening sensitivity and detected tumor size based on baseline mammographic density. BI-RADS-dependent sensitivity was estimated. The results of the 2.5 mg tamoxifen arm of the KARISMA trial were used to define expected changes in mammographic density after six months exposure and to predict changes in mammographic screening sensitivity and detected tumor size. Rates of interval cancers and detection of invasive tumors were estimated for women with mammographic density relative decreases by 10–50%. In all, 517 cancers in premenopausal women were diagnosed in KARMA: 287 (56%) screen-detected and 230 (44%) interval cancers. Screening sensitivities prior to tamoxifen, were 76%, 69%, 53%, and 46% for BI-RADS density categories A, B, C, and D, respectively. After exposure to tamoxifen, modelled screening sensitivities were estimated to increase by 0% (p = 0.35), 2% (p < 0.01), 5% (p < 0.01), and 5% (p < 0.01), respectively. An estimated relative density decrease by ≥20% resulted in an estimated reduction of interval cancers by 24% (p < 0.01) and reduction in tumors >20 mm at detection by 4% (p < 0.01). Low-dose tamoxifen has the potential to increase mammographic screening sensitivity and thereby reduce the proportion of interval cancers and larger screen-detected cancers.

Serum Phospholipid Fatty Acids and Mammographic Density in Premenopausal Women

The role of fatty acids (FAs) on mammographic density (MD) is unclear, and available studies are based on self-reported dietary intake. This study assessed the association between specific serum phospholipid fatty acids (PLFAs) and MD in premenopausal women. The cross-sectional study DDM-Madrid recruited 1392 Spanish premenopausal women, aged 39-50 y, who attended a screening in a breast radiodiagnosis unit of Madrid City Council. Women completed lifestyle questionnaires and FFQs. Percentage MD was estimated using a validated computer tool (DM-Scan), and serum PLFA percentages were measured by GC-MS. Multivariable linear regression models were used to quantify the association of FA tertiles with MD. Models were adjusted for age, education, BMI, waist circumference, parity, oral contraceptive use, previous breast biopsies, and energy intake, and they were corrected for multiple testing. Women in the third tertile of SFAs showed significantly higher MD compared with those in the first tertile (βT3vsT1=7.53; 95% CI: 5.44, 9.61). Elevated relative concentrations of palmitoleic (βT3vsT1=3.12; 95% CI: 0.99, 5.25) and gondoic (βT3vsT1=2.67; 95% CI: 0.57, 4.77) MUFAs, as well as high relative concentrations of palmitelaidic (βT3vsT1=5.22; 95% CI: 3.15, 7.29) and elaidic (βT3vsT1=2.69; 95% CI: 0.59, 4.79) trans FAs, were also associated with higher MD. On the contrary, women with elevated relative concentrations of n-6 (ω-6) linoleic (βT3vsT1=-5.49; 95% CI; -7.62, -3.35) and arachidonic (βT3vsT1=-4.68; 95% CI: -6.79, -2.58) PUFAs showed lower MD. Regarding desaturation indices, an elevated palmitoleic to palmitic ratio and a low ratio of oleic to steric and arachidonic to dihomo-γ-linolenic acids were associated with higher MD. Spanish premenopausal women with high relative concentrations of most SFAs and some MUFAs and trans FAs showed an increased MD, whereas those with high relative concentrations of some n-6 PUFAs presented lower density. These results, which should be confirmed in further studies, underscore the importance of analyzing serum FAs individually.

Abstract 3488: Associations of circulating hormones with mammographic density in postmenopausal women referred to diagnostic breast biopsy

Abstract Introduction Elevated mammographic density (MD) is a strong and independent risk factor for breast cancer, though underlying mechanisms are unclear. Prior studies have suggested that increased cumulative exposure to sex-steroid hormones and growth factors may impact both MD and MD-related breast cancer risk; however, most studies have only evaluated individual hormones. In this study, we simultaneously explored the relationship between 29 circulating hormones and growth factors with MD among postmenopausal women undergoing diagnostic breast biopsy. Methods We used data from 89 postmenopausal women, aged 44-65, who had complete measurements of 29 serum hormones from a single pre-biopsy blood draw (i.e., sex-steroid hormones: 15 estrogen/estrogen metabolites, 7 progesterone/progesterone metabolites; and non-sex hormones: insulin-like growth factor I and binding proteins (IGFBPs) 2-7). Volumetric MD (% fibroglandular volume) was assessed in pre-biopsy digital mammograms using single X-ray absorptiometry. Sufficient dimension reduction methods were used to compute a composite marker score that accommodates correlations among hormones and their relationship to MD. Backward elimination was applied to select log-transformed hormones contributing to the score at α=0.05; multivariable linear regression was used to further examine associations between selected hormones and MD within a single model, adjusting for age and BMI. Results Pearson correlations between hormones were moderate-to-strong. Dimension reduction methods identified 6 hormones as associated with MD (p&amp;lt;0.05): estradiol, 2-hydroxyestradiol, 2-methoxyestrone, 16-ketoestradiol, IGFBP-2, and 17α-hydroxyprogesterone, in models that considered MD as either continuous or dichotomous (&amp;gt;median vs. ≤median); BMI was consistently identified as the most significant predictor of MD (P &amp;lt;0.0001). In a multivariable linear regression model that included these 6 hormones, in addition to age and BMI, higher levels of 2-methoxyestrone, IGFBP-2, and 17α-hydroxyprogesterone were significantly associated with increased MD, whereas higher levels of age and BMI were significantly associated with lower MD. Conclusions We identified 6 out of 29 correlated hormones that were significantly associated with MD among postmenopausal women. For several, the directions of their associations with MD were comparable to those observed in prior studies that have separately evaluated these hormones in relation to breast cancer risk. We plan to further explore how circulating hormones concurrently affect MD in premenopausal women, accounting for menstrual cycle phase. Incorporation of dimension reduction methods in studies of multiple correlated hormones can help uncover new etiologic insights into the role of hormones and growth factors in MD and breast carcinogenesis and inform strategies for prevention. Citation Format: Shaoqi Fan, Ruth M. Pfeiffer, Manila Hada, Roni T. Falk, Maeve Mullooly, Hannah Oh, Berta Geller, Pamela Vacek, Donald Weave, John Shepherd, Jeff Wang, Sally Herschorn, Louise A. Brinton, Xia Xu, Mark E. Sherman, Britton Trabert, Gretchen L. Gierach. Associations of circulating hormones with mammographic density in postmenopausal women referred to diagnostic breast biopsy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3488.

Abstract 1585: Genetic variations in progesterone receptor (PGR)-related genes and mammographic density in premenopausal women: Are the associations mediated by circulating progesterone

Abstract BACKGROUND: Progesterone is a proliferative hormone in the breast. Combined estrogen plus progestin use in postmenopausal women increases mammographic density; a very strong risk for breast cancer. Circulating progesterone and genetic variations in progesterone receptor (PGR)-related genes are positively associated with mammographic density in postmenopausal women, but there are limited data in premenopausal women, with conflicting results. Notably, besides hormone therapy, genetic variation in PGR genes are known to modulate circulating progesterone levels. We, therefore, investigated the associations of genetic variations in PGR-related genes (PGR and Progesterone Receptor Membrane Component 1 (PGRMC1) with mammographic density in premenopausal women and determine, for the first time, whether these associations are mediated via circulating progesterone. METHODS: We genotyped 179 PGR-related single nucleotide polymorphisms (SNPs) (155 for PGR and 24 for PGRMC1 - 17 of which were synonymous variants and were filtered) in 364 cancer-free premenopausal women who had screening mammography at the Joanne Knight Breast Health Center at Washington University School of Medicine, St. Louis in 2016. We used Volpara to determine volumetric percent density, and dense volume. Variants were coded in dominant mode of inheritance. For causal mediation analysis, multivaraite linear regression models were applied to both the mediator (circulating PGR in logarithm scale) with variants and volumetric percent density, and dense volume with variant, PGR in logarithm scale and their interaction, both adjusting for age, body mass index, family history of breast cancer, and parity. The causal mediation effect, direct effect and total effect, by gentoype and averaged across genotypes were estimated with 95% confidence intervals and p values. Significance was claimed with p-value≤0.05. RESULTS: The mean age of the study participants was 47.5 years. Most participants (42.1%) had volumetric percent density between 3.5-7.5%, equivalent to BI-RADS® category b. Rs2020875 (PGR11) had a positive average direct effect (estimate=0.22, 95% CI, 0.016~0.44, p-value=0.024) and rs645213 (PGR11) had a borderline inverse direct effect (-0.25, -0.48~0.0004, p-value=0.052) on volumetric percent density. Further, rs11224565 (PGR11): 0.19, 0.04~0.34, p-value=0.028 had positive average direct effects on dense volume. None of the mediation effects were statistically signficiant. CONCLUSIONS: SNPs in PGR-related genes are associated with mammographic density in premenopausal women. Circulating progesterone levels did not mediate the associations between variants in PGR-related genes and mammographic density. Larger studies are needed to confirm our findings. Citation Format: Favour A. Akinjiyan, Yunan Han, Jingqin R. Luo, Aldi Kraja, Catherine M. Appleton, Graham A. Colditz, Adetunji T. Toriola. Genetic variations in progesterone receptor (PGR)-related genes and mammographic density in premenopausal women: Are the associations mediated by circulating progesterone [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1585.

Adolescent caffeine consumption and mammographic breast density in premenopausal women.

Previous studies suggest that coffee and caffeine intake may be associated with reduced breast cancer risk. To date, there is limited and inconsistent epidemiologic evidence for associations of adolescent diet with mammographic breast density, a strong and consistent predictor of breast cancer. We investigated the association of adolescent caffeine intake with mammographic density in premenopausal women. This study included 751 cancer-free women within the Nurses' Health Study II cohort. Percent breast density (PD), absolute dense (DA) and non-dense areas (NDA) were measured from digitized film mammograms using a computer-assisted thresholding technique; all measures were square root-transformed. Energy-adjusted adolescent caffeine intake was estimated using the data from a food frequency questionnaire. Information regarding breast cancer risk factors was obtained from questionnaires closest to the mammogram date. We used generalized linear regression to quantify associations of caffeine intake with breast density measures. In multivariable analyses, adolescent caffeine intake was not associated with any of the density phenotypes (caffeine 4th vs. 1st quartile: β = - 1.27, 95% CI - 4.62; 2.09, p-trend = 0.55 for percent density; β = - 0.21, 95% CI - 0.76, 0.34, p-trend = 0.65 for absolute dense area, and β = 0.23, 95% CI - 0.28, 0.74, p-trend = 0.50 for non-dense area). Additional adjustment of the models for body mass index at age 18 resulted in attenuation of the risk estimates. Our findings do not support the hypothesis that adolescent caffeine intake is associated with premenopausal mammographic breast density.

Abstract P4-10-08: Family history of breast cancer and mammographic density in premenopausal women

Abstract Introduction: Mammographic density and family history of breast cancer (FHBC) are independent risk factors for breast cancer. Women with dense breasts have a 4-6-fold increased risk of breast cancer and women with FHBC have a 1.5-3-fold increased risk of breast cancer. However, there is little data on the associations of FHBC with mammographic density, especially in premenopausal women. To address this, we investigated the associations of FHBC in first-degree relatives with mammographic density in premenopausal women. Methods: We used data from 375 cancer-free premenopausal women who were during routine screening mammography at Washington University in St. Louis in 2016. We used Volpara to measure volumetric measures of density including volumetric percent density, dense volume, and non-dense volume. We collected data on first-degree relatives (mother, sister) and numbers of first degree relatives (0, 1, ≥2) with a positive FHBC. We used multivariable linear regression model, adjusted for age, BMI, parity, race, age at menarche, and alcohol consumption, to determine the associations of FHBC and log-transformed volumetric percent density, dense volume, and non-dense volume. Beta coefficients (β) were evaluated and back transformed for easier interpretation. Results: The mean age of participants was 47.5 years (range=32-58). The mean BMI was 30.8 kg/m2 (range =17.9-63.1). Volumetric percent density was 25% (p-value&amp;lt;0.001) higher in women who had a FHBC compared with women who had no FHBC. The associations appeared confined to women with a positive family history in mothers but not those with a positive family history in sisters. Volumetric percent density was 31% higher (p-value&amp;lt;0.001) among women with a positive FHBC in mothers compared to those without a positive FHBC in mothers, but 8% higher (p-value=0.45) among women with a positive FHBC in sisters compared to those without a positive FHBC in sisters. The associations of FHBC with dense volume were similar to those of volumetric percent density in all the analyses. For instance, dense volume was 16% (p-value=0.006) higher in women who had a FHBC compared with women who had no FHBC. Table 1.Associations of family history of breast cancer (FHBC) and volumetric percent density (VPD), and dense volume (DV) in 375 premenopausal women*.FHBCNVPD (%) DV (cm3 ) Beta (95% CI)P-valueBeta (95% CI)P-valueNo275Ref Ref Yes871.25 (1.12,1.41)&amp;lt;0.0011.16 (1.04,1.29)0.007Unknown131.00 (0.76,1.30)0.990.74 (0.58,0.95)0.017*Adjusted for age, BMI, parity, race, age at menarche, and alcohol consumption. Conclusions: Premenopausal women with a first-degree FHBC have higher volumetric percent density. Our findings could help identify high-risk women who may benefit from targeted screening. Citation Format: Han Y, Zong X, Colditz GA, Toriola AT. Family history of breast cancer and mammographic density in premenopausal women [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-10-08.

Circulating Receptor Activator of Nuclear Factor-κB (RANK), RANK ligand (RANKL), and Mammographic Density in Premenopausal Women.

The receptor activator of nuclear factor-κB (RANK) pathway plays essential roles in breast development. Mammographic density is a strong risk factor for breast cancer, especially in premenopausal women. We, therefore, investigated the associations of circulating RANK and soluble RANK ligand (sRANKL) with mammographic density in premenopausal women. Mammographic density was measured as volumetric percent density in 365 cancer-free premenopausal women (mean age, 47.5 years) attending screening mammogram at the Washington University School of Medicine (St. Louis, MO). We used linear regression models adjusted for confounders, to compare the least-square means of volumetric percent density across tertiles of circulating RANK and sRANKL. Furthermore, because RANKL levels in mammary tissue are modulated by progesterone, we stratified analyses by progesterone levels. The mean volumetric percent density increased across tertiles of circulating RANK from 8.6% in tertile 1, to 8.8% in tertile 2, and 9.5% in tertile 3 (P trend = 0.02). For sRANKL, the mean volumetric percent density was 8.5% in tertile 1, 9.4% in tertile 2, and 9.0% in tertile 3 (P trend = 0.30). However, when restricted to women with higher progesterone levels, the mean volumetric percent density increased from 9.1% in sRANKL tertile 1 to 9.5% in tertile 2, and 10.1% in tertile 3 (P trend = 0.01). Circulating RANK was positively associated with volumetric percent density, while circulating sRANKL was positively associated with volumetric percent density among women with higher progesterone levels. These findings support the inhibition of RANKL signaling as a pathway to reduce mammographic density and possibly breast cancer incidence in high-risk women with dense breasts.

Milk intake and mammographic density in premenopausal women.

Mammographic density is a strong risk factor for breast cancer. Although diet is associated with breast cancer risk, there are limited studies linking adultdiet, including milk intake, with mammographic density. Here, we investigate the association of milk intake with mammographic density in premenopausal women. We analyzed data from 375 cancer-free premenopausal women who had routine screening mammography at Washington University School of Medicine, St. Louis, Missouri in 2016. We used Volpara to measure volumetric percent density, dense volume, and non-dense volume. We collected information on recent milk intake (past 12 months), and categorized skim milk and low/reduced-fat milk intake into 4 groups: < 1/week, 1/week, 2-6 times/week, ≥ 1/day, while whole and soy milk intake were categorized into 2 groups: < 1/week, ≥ 1/week. We used multivariable linear regression model to evaluate the associations of milk intake and log-transformed volumetric percent density, dense volume, and non-dense volume. In multivariable analyses, volumetric percent density was 20% (p-value = 0.003) lower in the 1/week group, 14% (p-value = 0.047) lower in the 2-6/week group, and 12% (p-value = 0.144) lower in the ≥ 1/day group (p-trend = 0.011) compared with women who consumed low/reduced-fat milk < 1/week. Attenuated and non-significant associations were observed for low/reduced-fat milk intake and dense volume. There were no associations of whole, skim, and soy milk intake with volumetric percent density and dense volume. Recent low/reduced-fat milk intake was inversely associated with volumetric percent density in premenopausal women. Studies on childhood and adolescent milk intake and adult mammographic density in premenopausal women are needed.

Milk intake and mammographic density in premenopausal women.

1569 Background: Mammographic density (MD), which reflects the amount of epithelial and stromal tissues in relation to adipose tissue in the breast, is a strong risk factor for breast cancer. Although diet is associated with breast cancer risk, studies evaluating the associations of adult diet with MD have mainly reported null associations. Few studies have, however, investigated the associations of dairy intake with MD, with conflicting results. Therefore, we investigated the associations of milk intake with MD in premenopausal women. Methods: We recruited 375 premenopausal women, with no history of cancer, who had routine screening mammography at the Breast Health Center, Washington University in St. Louis in 2016. We used Volpara to measure MD: volumetric percent density (VPD), dense volume (DV) and non-dense volume (NDV). In addition to known breast cancer risk factors, all participants completed a detailed questionnaire on milk intake (skim milk and 1%/2% milk were categorized into 4 groups: < once/week, once/week, 2-6 times/week, ≥once/day; whole and soy milk were categorized into 2 groups: < once/week, ≥once/week, because fewer women consumed them). We used multivariable linear regression models (adjusted for age, body mass index (BMI), parity, oral contraceptive use, family history of breast cancer, race) to evaluate the associations between milk intake and log transformed VPD, DV and NDV. Beta coefficients (β) were evaluated and back transformed for easier interpretation. Results: The mean age was 47.5 years (range: 32-58 years), mean VPD was 9.48%, mean DV was 80.69 cm3, and mean NDV was 1079 cm3. Compared with women who drank 1%/2% milk < once/week, VPD was 20% (p-value = 0.003) lower in the once/week group, 14% (p-value = 0.047) lower in the 2-6 times/week group, and 12% (p-value = 0.144) lower in the ≥once/day group. NDV was 19% (p-value = 0.039) lower among women who drank soy milk ≥once/week compared with women who drank < once/week. There were no associations of skim and whole milk with MD. Conclusions: We observed that 1%/2% milk intake was inversely associated with VPD, while soy milk intake was inversely associated with NDV. Further studies on how 1%/2% and soy milk intake impact MD are needed, as this could have implications in breast cancer prevention.

Adiposity at Age 10 and Mammographic Density among Premenopausal Women.

Although childhood adiposity is inversely associated with breast cancer risk, the association of childhood adiposity with mammographic density in premenopausal women has not been adequately studied. We analyzed data from 365 premenopausal women who came in for screening mammography at Washington University (St. Louis, MO) from 2015 to 2016. Body size at age 10 was self-reported using somatotype pictogram. Body mass index (BMI) at age 10 was imputed using data from Growing Up Today Study. Volpara software was used to evaluate volumetric percent density (VPD), dense volume (DV), and nondense volume (NDV). Adjusted multivariable linear regression models were used to evaluate the associations between adiposity at age 10 and mammographic density measures. Adiposity at age 10 was inversely associated with VPD and positively associated with NDV. A 1 kg/m2 increase in BMI at age 10 was associated with a 6.4% decrease in VPD, and a 6.9% increase in NDV (P < 0.001). Compared with women whose age 10 body size was 1 or 2, women with body size 3 or 4 had a 16.8% decrease in VPD and a 26.6% increase in NDV, women with body size 5 had a 32.2% decrease in VPD and a 58.5% increase in NDV, and women with body sizes ≥6 had a 47.8% decrease in VPD and a 80.9% increase in NDV (P < 0.05). The associations were attenuated, but still significant after adjusting for current BMI. Mechanistic studies to understand how childhood adiposity influences breast development, mammographic density, and breast cancer in premenopausal women are needed. Cancer Prev Res; 11(5); 287-94. ©2018 AACR.

Circulating Hormones and Mammographic Density in Premenopausal Women.

Prior research suggests that several endogenous hormones in premenopausal women are associated with breast cancer risk; however, few studies have evaluated associations of endogenous hormones with mammographic density (MD) in premenopausal women. We conducted a cross-sectional study of plasma hormone levels in relation to MD among 634 cancer-free premenopausal women in the Nurses' Health Study II. We measured percent MD from screening mammograms using a computer-assisted method. We assayed estradiol, estrone, and estrone sulfate in blood samples timed in early follicular and mid-luteal phases of the menstrual cycle as well as testosterone, androstenedione, progesterone, dehydroepiandrosterone (DHEA), DHEA sulfate, sex hormone-binding globulin (SHBG), and anti-Müllerian hormone in luteal or untimed samples. We used multivariable linear regression to quantify the association of %MD with quartiles of each hormone, adjusting for age, body mass index, and breast cancer risk factors. Women in the highest quartile of follicular estradiol levels had significantly greater %MD compared to those in the lowest quartile [difference, 6.7 percentage points; 95% confidence interval (CI) 2.2, 11.3; p-trend < 0.001]. Similar associations were observed for follicular free estradiol but not luteal-phase estradiol. Also, women in the top (vs. bottom) quartile of free testosterone had significantly lower %MD (difference, - 4.7; 95% CI - 8.7, - 0.8; p-trend = 0.04). Higher SHBG was significantly associated with higher percent MD (difference, 4.8; 95% CI 1.1, 8.6; p-trend = 0.002). Percent MD was not strongly associated with other measured hormones. Results were similar in analyses that excluded women with anovulatory cycles. Our findings suggest that follicular estradiol and SHBG may play an important role in premenopausal percent MD.

Alcohol consumption across the life course and mammographic density in premenopausal women.

Consumption of alcoholic beverages during adolescence and early adulthood has been consistently associated with higher breast cancer risk. The influence of alcohol consumption early in life on mammographic breast density, a marker of breast cancer risk, is inconclusive. This study examined associations of alcohol consumption across the life course with premenopausal mammographic density. The study population included 1211 premenopausal women in the Nurses' Health Study II without cancer, whorecalled their alcohol consumption at age 15 through enrollment in 1989 (baseline), and had mammograms available. Recent alcohol consumption was updated over follow-up. Percent and absolute measures of mammographic density were quantified on digitized film mammograms. Generalized linear regression was used to assess associations. There were no notable differences in any of the three density measures for alcohol consumption at any age (15-17, 18-22, 23-30, and 31-mammogram). Neither alcohol consumption before first pregnancy nor after first pregnancy was significantly associated with any of the three density measures. Moderate alcohol consumption during different age intervals during adolescence and early adulthood was not associated with mammographic density in premenopausal women.

Abstract 4248: Adiposity, change in adiposity during adulthood and mammographic density in premenopausal women

Abstract Background: Body mass index (BMI) is inversely associated with mammographic density among postmenopausal women, but few studies have evaluated this in premenopausal women. Further, there is limited data on the associations of weight change during adulthood with mammographic density. To address these, we investigated the associations of current adiposity measures, BMI at ages 18, 30, and changes in BMI at these age periods with volumetric mammographic density measures in 314 premenopausal women who underwent screening mammogram at the Breast Health Center, Washington University in St. Louis, MO. Methods: Study participants completed a questionnaire with information on breast cancer risk factors. Weight at ages 18 and 30 were self-reported. Current weight, height, waist, and body fat percent (%), were assessed by trained research personnel. BMIs were calculated as weight at each age/current height squared (kg/m2). We calculated weight change from; (i) age 18 to 30, (ii) age 18 to current age, (iii) age 30 to current age. Volpara was used to determine volumetric mammographic density measures. We investigated age-adjusted correlations between adiposity measures and mammographic density measures using Pearson correlation coefficients. We used multivariable linear regression models (adjusted for age, age at menarche, parity, age at each birth, family history of breast cancer, race, and education) to evaluate the associations of adiposity measures with mammographic density measures. Results: All adiposity and weight change measures were significantly inversely associated with percent density (PD), and positively associated with breast volume (BV). The strongest inverse correlations with PD were observed for body fat % (r= -0.68, P&amp;lt;0.001), and waist (r= -62, P&amp;lt;0.001). For BV, the strongest positive correlations were observed for waist r=0.75, P&amp;lt;0.001) and current BMI (r=0.76, P&amp;lt;0.001). In multivariable regression models, body fat % had the strongest association with PD (beta coefficient (ß)= -0.50, P&amp;lt;0.001). BMI during the three time points were each inversely associated with PD, with BMI at age 18 having the largest beta coefficient (ß= - 0.50, P&amp;lt;0.001) compared with current BMI (ß= -0.45, P&amp;lt;0.001) and BMI at age 30 (ß= - 40, P&amp;lt;0.001). After controlling for BMI at age 18, weight gain at all time periods was associated with a decrease in PD and an increase in BV. The largest decrease in PD was observed for weight gain from age 18 to current age (ß= - 8.5, P&amp;lt;0.001) comparing women who gained &amp;gt;25kg to those who had stable weight (gained between 0-5kg) during this period. Conclusions: Weight gain in early adulthood is associated with reductions in PD and increases in BV in premenopausal women. Our findings highlight the need for mechanistic studies focusing on early adulthood to provide a better understanding of how adiposity relates to mammographic density, and possibly breast cancer development in premenopausal women. Citation Format: Aliya Alimujiang, Graham Colditz, Catherine Appleton, Adetunji T. Toriola. Adiposity, change in adiposity during adulthood and mammographic density in premenopausal women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4248. doi:10.1158/1538-7445.AM2017-4248

Increased breast tissue receptor activator of nuclear factor-κB ligand (RANKL) gene expression is associated with higher mammographic density in premenopausal women.

Increased mammographic breast density is associated with a 4–6-fold increased risk of breast cancer, yet lifestyle factors that can reduce dense breasts are yet to be identified, and viable prevention strategies to reduce breast density-associated breast cancer development are yet to be developed. We investigated the associations of breast tissue receptor activator of nuclear factor-κB (RANK) pathway gene expression with mammographic density in 48 premenopausal women, with no previous history of cancer. Gene expression levels were measured in total RNA isolated from formalin-fixed paraffin-embedded breast tissue samples, using the NanoString nCounter platform. Mammographic density was classified based on the American College of Radiology Breast Imaging Reporting and Data (BI-RADS). Linear regression was used to evaluate associations between gene expression and mammographic density. The mean age of participants was 44.4 years. Women with higher breast tissue RANKL (TNFSF11) (p-value = 0.0076), and TNF (p-value = 0.007) gene expression had higher mammographic density. Our finding provides mechanistic support for a breast cancer chemoprevention trial with a RANKL inhibitor among high-risk premenopausal women with dense breasts.

Metabolic Syndrome and Mammographic Density in Premenopausal Chilean Women

ABSTRACTBackground: Metabolic syndrome (MetS) has been previously associated with an increased risk of breast cancer in postmenopausal women. Mammographic density (MD) is a marker of breast cancer risk. There is little evidence of an association between MetS and MD in premenopausal women. Methods: Through a cross-sectional study, we evaluated 364 premenopausal Chilean women in which we measured anthropometric, blood pressure, and metabolic markers. MetS and its components were defined according to the National Cholesterol Education Program Adult Treatment Plan III criteria. We estimated MD by absolute dense volume (ADV, cm3), nondense volume (NDV, cm3), and percentage of dense volume (PDV, %). The relationship between MetS and MD was assessed by linear regression models. Results: After adjusting for sociodemographic and gyneco-obstetrics variables, nonsignificant association was found between MetS and ADV (log β = 0.10; 95%CI: −0.01, 0.21). However, abdominal obesity, high triglycerides, and number of components of MetS were directly related to higher ADV (P < 0.05). Conclusion: Our results showed no association between MetS and ADV; nevertheless, abdominal obesity and triglycerides were related to higher ADV. If MD could be modifiable through nutritional factors, it would open new perspectives for the prevention of breast cancer through obesity prevention strategies at population level.

Influence of factors on mammographic density in premenopausal Chinese women.

Mammographic density is an independent strong risk factor for breast cancer. However, the influence of factors on mammographic density in premenopausal women remains unclear. In the Southern Professional Women Breast Cancer Screening Project, we assessed the associations between mammographic density and its influential factors using multivariate logistic regression in premenopausal women adjusting for BMI, age, duration of breastfeeding, number of live births, and breast size. A total of 1699 premenopausal women aged 27 to 57 years, who had been screened by mammography, were enrolled in this cross-sectional study. Overall, 85.2% were categorized as having dense breasts (BI-RADS density 3 and 4) and 14.8% as having fatty breasts (BI-RADS density 1 and 2). In multivariate and logistic regression analysis, only BMI and age were significantly negatively correlated with mammographic density in premenopausal women (P<0.001). No significant associations between mammographic density and number of deliveries, breastfeeding duration, education level, family history of breast cancer, as well as breast size and sleep quality, were identified in the study. Age and BMI are negatively associated with mammographic density in premenopausal Chinese women. Information on the influential factors of mammographic density in premenopausal women might provide meaningful insights into breast cancer prevention.

Adolescent intake of animal fat and red meat in relation to premenopausal mammographic density.

Adolescence is hypothesized to be a time period of particular susceptibility to breast cancer risk factors. Red meat and fat intake during high school was positively associated with risk of breast cancer among premenopausal women in the Nurses' Health Study II (NHSII). High mammographic density is a strong predictor of breast cancer risk but there is limited research on dietary factors associated with breast density. To test the hypothesis that high intake of animal fat or red meat during adolescence is associated with mammographic density, we analyzed data from premenopausal women in the NHSII. Participants recalled adolescent diet on a high school food frequency questionnaire. We assessed absolute and percent mammographic density on digitized analog film mammograms for 687 premenopausal women with no history of cancer. We used generalized linear regression to quantify associations of adolescent animal fat and red meat intake with mammographic density, adjusting for age, body mass index, and other predictors of mammographic density. Adolescent animal fat intake was significantly positively associated with premenopausal mammographic density, with a mean percent density of 39.2 % in the lowest quartile of adolescent animal fat intake versus 43.1 % in the highest quartile (p trend: 0.03). A non-significant positive association was also observed for adolescent red meat intake (p trend: 0.14). These findings suggest that higher adolescent animal fat intake is weakly associated with percent mammographic density in premenopausal women.