Abstract
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.
Highlights
Systemic inflammation may play a role in shaping breast composition, one of the strongest risk factors for breast cancer
Study population The present study includes 397 girls participating in the Growth and Obesity Cohort Study (GOCS) in Santiago, Chile, for whom blood samples were collected at Tanner’s rating scale (Tanner) stages 2 and/or 4 and breast density was measured at Tanner stage 4
Of the 397 girls with inflammatory measurements at Tanner stage 2, 119 were lost to follow-up or did not consent to provide breast composition measurements at Tanner stage 4. These 119 participants tended to be older at the Tanner stage 2 visit, have a higher fat body fat percentage, and have higher levels of each inflammatory marker (Additional file 1)
Summary
Systemic inflammation may play a role in shaping breast composition, one of the strongest risk factors for breast cancer. The association between chronic inflammation and tumorigenesis may be driven by an impact of inflammation on estrogen synthesis, as well as general cell proliferation, insulin resistance, and insulin-like growth factor I [2,3,4] These downstream impacts of chronic inflammation may shape breast composition, one of the strongest predictors of breast cancer risk [5]. Pro-inflammatory markers, such as interleukin-6 (IL6), tumor necrosis factor α (TNFα), and C-reactive protein (CRP), elevate in response to infection, tissue damage, and in active stressed states such as obesity [6] These persistent triggering factors may disrupt the balance between the expressions of pro- and antiinflammatory markers and initiate sustained subclinical systemic inflammation. They may suppress the antitumor immune response and increase estrogen levels in breast tissue, which all may directly promote the steps of neoplastic transformation through increased breast density [7]
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