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

Abstract

Objective: To investigate the association between gut microbiome with breast tumor characteristics (receptor status, stage and grade) and known breast cancer risk factors.

Methods: In a pilot cross-sectional study of 37 incident breast cancer patients, fecal samples collected prior to chemotherapy were analyzed by 16S ribosomal RNA (rRNA) gene-based sequencing protocol. Alpha diversity and specific taxa by tumor characteristics and breast cancer risk factors were tested by Wilcoxon rank sum test, and by differential abundance analysis, using a zero-inflated negative binomial regression model with adjustment for total counts, age and race/ethnicity.

Results: There were no significant alpha diversity or phyla differences by estrogen/progesterone receptor status, tumor grade, stage, parity and body mass index. However, women with human epidermal growth factor receptor 2 positive (HER2+) (n = 12) compared to HER2- (n = 25) breast cancer showed 12-23% lower alpha diversity [number of species (OTU) p = 0.033, Shannon index p = 0.034], lower abundance of Firmicutes (p = 0.005) and higher abundance of Bacteroidetes (p = 0.089). Early menarche (ages ≤ 11) (n = 11) compared with later menarche (ages ≥ 12) (n = 26) was associated with lower OTU (p = 0.036), Chao1 index (p = 0.020) and lower abundance of Firmicutes (p = 0.048). High total body fat (TBF) (> 46%) (n = 12) compared to lower (≤ 46%) TBF was also associated with lower Chao 1 index (p = 0.011). There were other significant taxa abundance differences by HER2 status, menarche age, as well as other tumor and breast cancer risk factors.

Conclusions and relevance: Further studies are needed to identify characteristics of the human microbiome and the interrelationships between breast cancer hormone receptor status and established breast cancer risk factors.

Keywords: Age at menarche; HER2 status; Microbiome; Tumor characteristics.

Fig. 1

Collection of baseline (B) and last (L) fecal samples from study participants

Fig. 2

Beta-diversity results by baseline body mass index are shown: A unweighted UniFrac-based principal component analysis plot of the first two principal coordinates categorized by body mass index (BMI < 25 kg/m²n = 9, BMI ≥ 25 kg/m²n = 28). Axis 1 explained 20.9% while axis 2 explained 10.5% of the variance. B Weighted UniFrac-based principal component of the first two principal coordinates categorized by BMI; axis 1 explained 25.1% and axis 2 explained 10.3% of the variance

Fig. 3

Relative abundance levels of the most frequent phyla among A breast cancer patients with HER2+ tumors (n = 12) vs HER2− tumors (n = 25), and B breast cancer patients with early age at menarche (≤ 11) (n = 11) vs later age at menarche (≥ 12) (n = 26) are shown. Wilcoxon rank sum test was used to test for phylum-level differences by HER2 status and by age at menarche. p values are listed above each phylum

Fig. 4

Relative abundance levels (mean, median, minimum and maximum) of Firmicutes by four groups of breast cancer patients are shown: HER2− breast cancer and later age at menarche (≥ 12) (n = 18), HER2+ breast cancer and late age at menarche (n = 8), HER− breast cancer and early age at menarche (≤ 11) (n = 7), and HER2+ breast cancer and early age at menarche (n = 4)

Fig. 5

Relative abundance levels of select genera of Firmicutes by HER2 status are shown. Wilcoxon rank sum test was used to test for genus-level differences by HER2 status. p values are listed above each genus