Cancer Diagnosis Program | Biorepositories and Biospecimen Research Branch

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

Author(s): Wu AH, Tseng C, Vigen C, Yu Y, Cozen W, Garcia AA, Spicer D

Publication: Breast Cancer Res Treat, 2020, Vol. 182, Page 451-463

PubMed ID: 32468338 PubMed Review Paper? No

Purpose of Paper

Conclusion of Paper

Studies

1. Study Purpose

   This study investigated correlations between fecal microbial profiles and patient age, menopausal status, age at menarche, BMI, total body fat, parity, physical activity, and tumor characteristics (receptor status, tumor grade, tumor stage) in specimens from breast cancer patients. Fecal specimens were self-collected by 37 breast cancer patients [average age= 50.6 ± 12.3; 20 premenopausal, 17 postmenopausal; 29 parous, 8 nulliparous; mean age of menarche=12.4 ± 1.5; average BMI - 30.6 ± 7.9 kg/m2; average total body fat= 42.7% ± 6.9; 22 early stage (I/II) and 23 high grade tumors; 23 ER+PR+, 5 ER+PR-; 9 ER-PR-; 25 HER2 negative, 12 HER2 positive] after surgery but before chemotherapy. Specimens were collected using fecal collection kits and stored in in the participants’ freezers until picked up by study staff or brought in by the participants. Specimens were then stored at -80°C until DNA extraction using an unspecified method. The bacterial 16S rRNA gene V4 region was amplified by PCR and sequenced on a MiSeq platform. Alpha diversity was assessed by operational taxonomic units (OTUs) counts, Chao1 as an estimate of species richness, Shannon diversity index to measure richness and evenness, and phylogenetic distance. Wilcoxon rank sum test was used to examine differences in alpha diversity between any two groups and Kruskal–Wallis between any three groups. Beta diversity was assessed using weighted and unweighted UniFrac-based principal component analysis. Permutational multivariate analysis of variance (PERMANOVA) was performed to determine statistical significance of microbial composition and patient age (<50, 50+), menopausal status (pre-menopause, postmenopause), age at menarche (≤11, ≥12), BMI (<25, ≥25), total body fat (≤46%, >46%), parity (nulliparous, parous), physical activity (no, yes), and tumor characteristics including stage (I/II, III), grade (I/II, III), receptor status (ER+PR+, ER+PR−, ER−PR−), and HER2 status (HER2 negative, HER2 positive).

   Summary of Findings:

   Beta diversity was significantly different among fecal specimens grouped by patient BMI (<25 versus ≥25 kg/m2) and total body fat (≤46%, >46%) when analyzed by weighted principal component analysis (P=0.009 and P=0.048, respectively) but was not associated with any other factors investigated. Fecal specimens from HER2-positive patients showed 12–23% lower alpha diversity as determined by lower numbers of OTUs and Shannon index (P=0.033 and P=0.034, respectively) compared to fecal specimens from HER2-negative patients. High total body fat (>46%) compared to lower total body fat (≤46%) was associated with lower Chao 1 index (P=0.011). Fecal specimens from patients with early menarche (ages ≤11) were associated with lower OTUs (P=0.036) and Chao1 index (P=0.020) compared to specimens from patients with later menarche (ages ≥12). Fecal specimens from physically active patients had a higher Chao 1 index (P=0.07) and OTUs (P=0.58) than those who were not physically active but Shannon index and phylogenetic distance were comparable. There were no significant differences in alpha diversity or phyla differences when patients were grouped by age, estrogen/progesterone receptor status, tumor grade, tumor stage, parity, or body mass index (BMI). Relative abundances of 13 taxa differed significantly in specimens from HER2 positive and HER2 negative patients, three taxa differed between feces from ER+ and ER− patients, and two taxa differed between feces from PR+ and PR− patients (P≤0.001, all). Four taxa were more abundant in feces from patients with higher grade (III) tumors compared to those with lower grade (I/II) tumors (P≤0.001, all) while specimens from patients with higher stage breast cancers were associated with higher abundances of three taxa but lower abundances of two taxa compared to specimens from patients with lower stage breast cancers (P≤0.001, all). Significant differences in relative abundance of select taxa were also observed between feces when patients were grouped based on age, menarche age, parity, BMI, total body fat, and physical activity (P<0.0001, all).

   Biospecimens

   • Bodily Fluid - Feces

   Preservative Types

   • Frozen

   Diagnoses:

   • Neoplastic - Carcinoma

   Platform:

   Analyte	Technology Platform
   RNA	RT-PCR
   RNA	Next generation sequencing

   Pre-analytical Factors:

   Classification	Pre-analytical Factor	Value(s)
   Preaquisition	Patient age	<50 50+
   Next generation sequencing Specific	Targeted nucleic acid	Bacterial 16S rRNA gene V4 region
   Preaquisition	Diagnosis/ patient condition	menopausal status age at menarche (≤11, ≥12) total body fat (≤46%, >46%) parity (nulliparous, parous) physical activity (no, yes) Tumor stage (I/II, III) Tumor grade (I/II, III) Receptor status (ER+PR+, ER+PR−, ER−PR−) HER2 status (HER2−, HER2+)
   Preaquisition	Patient body mass index	<25 kg/m2 ≥25 kg/m2

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