Birth Sex-Ratio Imbalance and Global Breast Cancer Mortality: A Robustness-Focused Ecological Panel Analysis

Abstract

This study evaluates whether birth sex-ratio imbalance has an independent ecological association with breast cancer mortality in country-year panel data. Country-year data for 1990-2023 were assembled from GBD/IHME, World Bank, and WHO Global Health Observatory sources. The manuscript framing and literature audit used a multi-perspective workflow: question generation, source-grounded evidence curation, outline synthesis, and blind-spot review. The empirical analysis used a descriptive nested ordinary least squares model ladder, country-clustered standard errors, country/year fixed-effects robustness checks, lagged predictors, registry-quality sensitivity analysis, and leave-one-country-out validation. Adding SRB imbalance produced a very small incremental gain beyond incidence and standard ecological adjustment variables (R² gain = 0.000783). SRB was statistically significant under heteroskedasticity-robust standard errors, but not under country-clustered inference (p = 0.160548). SRB also remained non-significant after observed adjustment covariates, two-way country/year fixed effects, lagged temporal checks, and alternative natural-baseline assumptions of 1.03, 1.05, and 1.07. Overall, SRB provided at most a small, non-robust ecological signal and should not be interpreted as an independent breast cancer mortality determinant.