Background: Frequent dairy consumption in childhood has been related to higher growth-hormone concentrations that may affect mammary gland and pubertal development.Objective: We evaluated the relation of dairy intake to breast composition at Tanner stage 4 and age at menarche.Design: A total of 515 Chilean girls are included in the Growth and Obesity Cohort Study. The subjects have been followed longitudinally since they were 3-4 y old (from 2006 to the present). Starting in 2013, diet was assessed every 6 mo via a 24-h recall. The breast fibroglandular volume (FGV) was measured with the use of dual-energy X-ray absorptiometry at Tanner stage 4. The date of menarche was reported every 6 mo. Our analysis included 290 girls with data on prospective diet and breast composition and 324 girls with data on prospective diet and age at menarche.Results: The mean ± SD breast FGV and percentage of fibroglandular volume (%FGV) (i.e., FGV divided by total breast volume times 100) at Tanner stage 4 was 81.7 ± 32.2 cm³ and 42.0% ± 16.7%, respectively. Only sweetened, artificially flavored milk-based drinks were associated with the %FGV with girls who consumed >125 g/d having a %FGV that was 4.5% (95% CI: 0.9%, 8.1%) higher than that of girls who consumed none (P-trend = 0.007). Yogurt intake was associated with a lower FGV. Specifically, girls who consumed >125 g yogurt/d had -10.2 cm³ (95% CI: -20.2, -0.3 cm³) less FGV than did girls who consumed no yogurt (P-trend = 0.03). The majority (90.7%) of girls in our cohort attained menarche before the data analyses with a mean ± SD age at menarche of 11.9 ± 0.7 y. In multivariable models, low-fat dairy, low-fat milk, and yogurt intakes were associated with a later age at menarche. In particular, girls who consumed >125 g yogurt/d had menarche, on average, 4.6 mo (95% CI: 1.9, 7.4 mo) later than girls who consumed no yogurt (P-trend = 0.01).Conclusion: More-frequent consumption of sweetened, artificially-flavored milk-based drinks is associated with a higher %FGV, whereas higher yogurt intake is associated with a lower FGV and delayed age at menarche in 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 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.

Conclusion

Overall, we observed no evidence that SSB intake was associated with breast density in adolescent Chilean girls.

Background

Systemic 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.

Methods

We 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.

Results

In 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.

Conclusions

Systemic 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.

BACKGROUND:The age of menarche has been associated with metabolic and cardiovascular disease, as well as cancer risk. The decline in menarcheal age over the past century may be partially attributable to increased exposure to endocrine disrupting chemicals (EDCs). METHODS:We assessed the influence of 26 phenol and phthalate biomarkers on the timing of menarche in a longitudinal cohort of Chilean girls. These EDCs were quantified in urine collected prior to the onset of breast development (Tanner 1; B1), and during adolescence (Tanner 4; B4). Multivariable accelerated failure time (AFT) models were used to analyze associations between biomarker concentrations and the age of menarche adjusting for body mass index (BMI) Z-score and maternal education, accounting for within-subject correlation. RESULTS:Several biomarkers were significantly associated with the age at menarche; however, these associations were dependent on the timing of biomarker assessment. A log(ng/ml) increase in B1 concentrations of di(2-ethylhexyl) phthalate biomarkers was associated with later menarche (hazard ratio (HR): 0.77; 95% CI: 0.60, 0.98), whereas higher B1 concentrations of 2,5-dichlorophenol and benzophenone-3 were associated with earlier menarche (HR: 1.13; 95% CI: 1.01, 1.27; HR: 1.17; 95% CI: 1.06, 1.29, respectively). Elevated B4 concentrations of monomethyl phthalate were similarly associated with earlier menarche (HR: 1.30; 95% CI: 1.10, 1.53). The impact of monoethyl phthalate and triclosan concentrations on pubertal timing were significantly modified by BMI Z-score. Higher monoethyl phthalate and triclosan concentrations were associated with earlier menarche among overweight or obese girls, but not among those that were normal weight. CONCLUSIONS:This study identifies modulation of sexual maturation by specific EDC biomarkers in Latina girls.

Background

During puberty, mammary tissue undergoes rapid development, which provides a window of heightened susceptibility of breast composition to the influence of endogenous and exogenous hormones. Exposure to endocrine-disrupting chemicals (EDC) may affect breast development and composition and the risk of developing breast cancer in adulthood.

Methods

We evaluated the associations between breast density and urinary concentrations of phenols and phthalates collected at Tanner 1 (B1) and Tanner 4 (B4) in 200 Chilean girls. Total breast volume (BV), fibroglandular volume (FGV), and percent dense breast (%FGV) were evaluated at B4 using dual X-ray absorptiometry. Generalized estimating equations were used to analyze the association between concentrations of EDC biomarkers across puberty and breast density.

Results

The geometric mean %FGV was 7% higher among girls in the highest relative to the lowest tertile of monocarboxyisooctyl phthalate [1.07; 95% confidence interval (CI), 1.01-1.14]. Monoethyl phthalate concentrations at B4 were positively associated with FGV (highest vs. lowest tertile: 1.22; 95% CI, 1.06-1.40). Bisphenol A displayed a U-shaped association with FGV; girls in the middle tertile had at least 10% lower FGV than girls in the lowest or highest tertiles. Monocarboxyisononyl phthalate showed a nonlinear association with BV. No other statistically significant associations were observed.

Conclusions

Our results suggest that the developing breast tissue is susceptible to select EDCs during childhood and adolescence.

Impact

This study may spur further investigations into environmental influences on breast development during puberty and how shifts in pubertal breast density track through the life course to modify breast cancer risk.

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 (R^{2 =} 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.

Following a 2019 workshop led by the Center for Global Health Studies at the Fogarty International Center on the topic of childhood obesity prevention and research synergies transpiring from cross-border collaborations, we convened a group of experts in the United States and Latin America to conduct a narrative review of the epidemiological literature on the role of obesogenic endocrine disrupting chemicals (EDCs) in the etiology of childhood obesity among Latino youth in the United States and Latin America. In addition to summarizing and synthesizing results from research on this topic published within the last decade, we place the findings within a lifecourse biobehavioral framework to aid in identification of unique exposure-outcome relationships driven by both biological and behavioral research, identify inconsistencies and deficiencies in current literature, and discuss the role of policy regulations, all with the goal of identifying viable avenues for prevention of early life obesity in Latino/Hispanic populations.