Associations of fecal microbial profiles with breast cancer and non-malignant breast disease in the Ghana Breast Health Study

The gut microbiota may play a role in breast cancer etiology by regulating hormonal, metabolic, and immunologic pathways. We investigated associations of fecal bacteria with breast cancer and non-malignant breast disease in a case-control study conducted in Ghana, a country with rising breast cancer incidence and mortality. To do this, we sequenced the V4 region of the 16S rRNA gene to characterize bacteria in fecal samples collected at the time of breast biopsy (N=379 breast cancer cases, N=102 non-malignant breast disease cases, N=414 population-based controls). We estimated associations of alpha diversity (observed amplicon sequence variants [ASVs], Shannon index, and Faith’s phylogenetic diversity), beta diversity (Bray Curtis and unweighted/weighted UniFrac distance), and presence and relative abundance of select taxa with breast cancer and non-malignant breast disease using multivariable unconditional polytomous logistic regression. All alpha diversity metrics were strongly, inversely associated with odds of breast cancer and for those in the highest vs. lowest tertile of observed ASVs, the odds ratio (95% confidence interval) was 0.21 (0.13-0.36; Ptrend<0.001). Alpha diversity associations were similar for non-malignant breast disease and breast cancer grade/molecular subtype. All beta diversity distance matrices and multiple taxa with possible estrogen-conjugating and immune-related functions were strongly associated with breast cancer (all P’s<0.001). There were no statistically significant differences between breast cancer and non-malignant breast disease cases in any microbiota metric. In conclusion, fecal bacteria characteristics were strongly and similarly associated with breast cancer and non-malignant breast disease. Our findings provide novel insight into potential microbially-mediated mechanisms of breast disease. Novelty and impact: Our study is the largest study to investigate associations of the fecal microbiota with breast cancer to date, and the first to investigate these associations in Sub-Saharan Africa, a population with rising breast cancer incidence and mortality. Our findings set up intriguing hypotheses whereby the gut microbiota may be associated with breast disease and motivate continued study of gut microbiota-breast disease/breast cancer associations in diverse study populations.