Gut microbiome associations with breast cancer risk factors and tumor characteristics: a pilot study Original paper

What was studied?

The focus keyphrase gut microbiome breast cancer risk factors appears within this paragraph. This study investigated how the gut microbiome varies in relation to breast cancer risk factors and tumor characteristics, aiming to clarify whether microbial diversity or specific taxa differ by features such as HER2 status, hormone receptor status, tumor grade, stage, obesity measures, early menarche, and reproductive history. Using pre-treatment fecal samples from women newly diagnosed with breast cancer, the researchers applied 16S rRNA sequencing to quantify microbial diversity and taxonomic composition. This exploratory work sought to identify microbial signatures that may be relevant to breast cancer biology and to the development of a microbiome signatures database. Visual data from the paper, including boxplots on pages 6–8, illustrate phylum-level and genus-level differences linked to HER2 status and age at menarche, helping clarify how microbial distributions shift across clinically meaningful subgroups.

Who was studied?

The study enrolled 37 women with incident invasive breast cancer from Los Angeles County, predominantly Hispanic (73%) and largely overweight or obese (75%). All provided a fecal sample collected before chemotherapy. Participants ranged in age from premenopausal to postmenopausal, with a mean baseline BMI of 30.6 kg/m² and a mean total body fat (TBF) of 42.7%. Tumor profiles included HER2– (67.6%), ER+/PR+ (62.2%), and mostly high-grade (grade III) cancers. Exclusion criteria ensured participants were free from prior cancers, inflammatory bowel disease, recent antibiotics, or probiotic use. This population allowed evaluation of microbiome structure across key risk factors such as age at menarche, parity, adiposity, and physical activity.

Most important findings

Women with HER2+ breast cancer showed markedly lower alpha diversity—12–23% reductions in OTU counts, Chao1, and Shannon indices—supported by boxplots on page 5. They also had lower Firmicutes abundance and higher Bacteroidetes representation (page 6). Taxonomic models revealed 13 significantly altered taxa for HER2 status: HER2+ tumors displayed higher Enterococcus, Acidaminococcus, and Alistipes, but much lower Ruminococcus, Blautia, Coprococcus, Christensenellaceae, and Methanobrevibacter. These patterns suggest reduced representation of taxa associated with metabolic health and SCFA (short-chain fatty acid) production. Early menarche (≤11 years) was strongly associated with lower alpha diversity, lower Firmicutes abundance (page 6), and multiple taxa reductions—including Ruminococcaceae, Lachnobacterium, Anaerostipes, and Turicibacter—all microbes linked to SCFA metabolism, gut barrier integrity, and estrogen-microbiome interactions. Higher total body fat (>46%) and higher BMI mirrored these diversity reductions, with elevated Clostridiaceae and reduced Lactobacillus, Streptococcus, and Catenibacterium. Progressive Firmicutes decline when HER2 positivity and early menarche co-occur. Higher tumor stage and grade correlated with increased Clostridium, Veillonella, and Haemophilus, suggesting shifts toward pro-inflammatory or dysbiotic profiles.

Key implications

These findings underscore the potential interplay between host endocrine–metabolic factors and gut microbial composition in breast cancer. The distinct microbial signatures associated with HER2 status—particularly depleted Ruminococcaceae and Lachnospiraceae and increased Enterococcus—suggest that microbiome alterations may accompany or contribute to tumor biology. Early menarche and high adiposity, established breast cancer risk factors, also show consistent microbial correlates, supporting the concept of a gut–estrogen–metabolism axis relevant to cancer development. Although exploratory, these microbial patterns may eventually support biomarker development for risk stratification or treatment personalization, pending validation in larger cohorts.

Citation

Wu AH, Tseng C, Vigen C, Yu Y, Cozen W, Garcia AA, Spicer D. Gut microbiome associations with breast cancer risk factors and tumor characteristics: a pilot study. Breast Cancer Research and Treatment. 2020;182:451-463. doi:10.1007/s10549-020-05702-6