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

BACKGROUND: Epidemiologic 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. METHODS: In 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. RESULTS: Urinary 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 (ß = -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. CONCLUSIONS: Our 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.

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

BACKGROUND: Frequent 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. METHODS: We 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. RESULTS: A 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 ß: - 5.4, 95% CI - 15.1, 4.4; Q3 vs Q1 ß: 1.3, 95% CI - 8.6, 11.3; Q4 vs Q1 ß: 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. CONCLUSION: Overall, 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.