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

• Published in: Breast cancer research and treatment 2020-07, Vol.182 (2), p.451-463
• Main Authors: Wu, Anna H., Tseng, Chiuchen, Vigen, Cheryl, Yu, Yang, Cozen, Wendy, Garcia, Agustin A., Spicer, Darcy
• Format: Article
• Language: English
• Subjects: Abundance; Adult; Age Factors; Aged; Bacteroidetes - genetics; Bacteroidetes - isolation & purification; Biomarkers, Tumor - metabolism; Body fat; Body Mass Index; Breast - pathology; Breast cancer; Breast Neoplasms - epidemiology; Breast Neoplasms - pathology; Breast Neoplasms - physiopathology; Cancer research; Chemotherapy; Cross-Sectional Studies; Digestive system; DNA, Bacterial - isolation & purification; Epidemiology; Epidermal growth factor; ErbB-2 protein; Estrogens; Feces - microbiology; Female; Firmicutes; Firmicutes - genetics; Firmicutes - isolation & purification; Gastrointestinal Microbiome - physiology; Health risk assessment; Humans; Intestinal microflora; Medicine; Medicine & Public Health; Menarche; Menarche - physiology; Microbiomes; Microbiota; Middle Aged; Oncology; Parity - physiology; Pilot Projects; Progesterone; Receptor, ErbB-2 - metabolism; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; Risk Factors; RNA, Ribosomal, 16S - genetics; rRNA 16S
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-020-05702-6

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.