Chronic systemic inflammation is hypothesised to promote carcinogenesis by creating a tissue environment that facilitates malignant transformation. In the context of obesity, expansion and dysfunction of white adipose tissue increase secretion of pro- and anti-inflammatory adipokines and cytokines, which may influence breast cancer risk after menopause. The inflammatory pathway can interact with other biological systems implicated in postmenopausal breast carcinogenesis, including insulin/IGF signalling and sex-steroid hormone synthesis via effects on aromatase.
Laboratory and epidemiological evidence has particularly implicated C-reactive protein (CRP), leptin, and adiponectin in postmenopausal breast cancer risk: CRP has been associated with higher risk in several meta-analyses, leptin is generally positively associated, and adiponectin is typically inversely associated in experimental studies. However, epidemiological data on many cytokines and anti-inflammatory markers remain limited. The study reported here aimed to estimate effects of circulating inflammatory biomarkers on the risk of postmenopausal ER-positive breast cancer using a case-cohort design nested in the Melbourne Collaborative Cohort Study.
The analysis used a case-cohort sample drawn from the Melbourne Collaborative Cohort Study. The included analytic sample comprised 1,223 females who were postmenopausal at the time of blood collection, among whom 347 developed ER-positive breast cancer (cases). The study applied a case-cohort framework to evaluate associations between pre-diagnostic circulating biomarkers and subsequent ER-positive breast cancer.
A range of inflammatory markers and adipokines were measured in blood samples. For each biomarker, associations with ER-positive breast cancer were estimated in two ways: (1) per doubling of biomarker concentration, and (2) by comparing quartiles of concentration with the lowest quartile as reference. Estimates were derived using weighted Poisson regression with a robust variance estimator to account for the case-cohort design. The provided summary reports risk ratios (RRs) and 95% confidence intervals (CIs) for each marker. Specific details on laboratory assays, covariates included in adjusted models, and follow-up duration are available in the full article but are not reported in the provided source excerpt.
When modelled per doubling in plasma concentration, several biomarkers showed positive point estimates for ER-positive breast cancer risk. The principal findings reported in the abstract were:
Leptin: RR 1.13 (95% CI 1.03–1.25) per doubling, indicating a statistically significant positive association.
Interleukin-10 (IL-10): RR 1.14 (95% CI 1.01–1.29) per doubling, also reaching statistical significance.
Adiponectin: RR 1.10 (95% CI 0.90–1.34) per doubling; point estimate above unity but CI included the null.
Tumour necrosis factor-alpha (TNF-α): RR 1.27 (95% CI 0.96–1.68) per doubling; elevated point estimate though CI overlapped 1.00.
Other inflammatory markers showed effect estimates close to the null per doubling: interferon-gamma RR 1.04 (95% CI 0.93–1.17), interleukin-6 (IL-6) RR 1.01 (95% CI 0.88–1.17), interleukin-8 RR 0.98 (95% CI 0.83–1.16), and C-reactive protein (CRP) RR 1.03 (95% CI 0.95–1.11).
The authors also report analyses by quartile of biomarker concentration and examined the leptin-to-adiponectin ratio. The leptin-to-adiponectin ratio had an RR per doubling of 1.07 (95% CI 0.99–1.16). Quartile-specific results and tests for trend are reported in the full manuscript; detailed quartile estimates beyond the leptin-to-adiponectin ratio are not provided in the abstract excerpt.
The report summarises mechanistic pathways supporting an inflammatory contribution to postmenopausal ER-positive breast cancer. Adipose tissue expansion in obesity raises leptin production and can cause local hypoxia, adipocyte cell death and macrophage recruitment, all of which increase secretion of pro-inflammatory cytokines such as TNF-α and IL-6. These cytokines can stimulate aromatase activity in adipose tissue, potentially increasing local oestrogen production. Adiponectin, an anti-inflammatory adipokine reduced in obesity, has insulin-sensitising and anti-proliferative properties in laboratory studies and therefore could plausibly protect against breast carcinogenesis. Chronic inflammation can also contribute to insulin resistance, linking inflammation to metabolic pathways relevant to cancer development.
In this case-cohort analysis of postmenopausal females, higher circulating leptin and IL-10 concentrations were associated with an increased risk of developing ER-positive breast cancer, while other biomarkers showed smaller or null associations in the reported per-doubling analyses. The authors conclude that systemic inflammation may be important in the aetiology of postmenopausal ER-positive breast cancer.
These findings add to mechanistic and epidemiological evidence connecting obesity-related inflammation, adipokine imbalance and pro-inflammatory cytokines with breast cancer risk after menopause. The study suggests that inflammatory pathways could represent targets for prevention strategies in postmenopausal females, particularly those with obesity or low physical activity. Specific recommendations, assay details, covariate adjustment and sensitivity analyses are described in the full article; those details were not included in the provided source excerpt.