Intestinal Microbiota in Postmenopausal Breast Cancer Patients and Controls

Abstract

Background: Previous preclinical and clinical research has investigated the role of intestinal microbiota in carcinogenesis. Growing evidence exists that intestinal microbiota can influence breast cancer carcinogenesis. However, the role of intestinal microbiota in breast cancer needs to be further investigated. This study aimed to identify the microbiota differences between postmenopausal breast cancer patients and controls. Patients and methods: This prospective cohort study compared the intestinal microbiota richness, diversity, and composition in postmenopausal histologically proven ER+/HER2- breast cancer patients and postmenopausal controls. Patients scheduled for (neo)adjuvant adriamycin, cyclophosphamide (AC), and docetaxel (D), or endocrine therapy (tamoxifen) were prospectively enrolled in a multicentre cohort study in the Netherlands. Patients collected a faecal sample and completed a questionnaire before starting systemic cancer treatment. Controls, enrolled from the National Dutch Breast Cancer Screening Programme, also collected a faecal sample and completed a questionnaire. Intestinal microbiota was analysed by amplicon sequencing of the 16S rRNA V4 gene region. Results: In total, 81 postmenopausal ER+/HER2- breast cancer patients and 67 postmenopausal controls were included, resulting in 148 faecal samples. Observed species richness, Shannon index, and overall microbial community structure were not significantly different between breast cancer patients and controls. There was a significant difference in overall microbial community structure between breast cancer patients scheduled for adjuvant treatment, neoadjuvant treatment, and controls at the phylum (p = 0.042) and genus levels (p = 0.015). Dialister (p = 0.001) and its corresponding family Veillonellaceae (p = 0.001) were higher in patients scheduled for adjuvant treatment, compared to patients scheduled for neoadjuvant treatment. Additional sensitivity analysis to correct for the potential confounding effect of prophylactic antibiotic use, indicated no differences in microbial community structure between patients scheduled for neoadjuvant systemic treatment, adjuvant systemic treatment, and controls at the phylum (p = 0.471) and genus levels (p = 0.124). Conclusions: Intestinal microbiota richness, diversity, and composition are not different between postmenopausal breast cancer patients and controls. The increased relative abundance of Dialister and Veillonellaceae was observed in breast cancer patients scheduled for adjuvant treatment, which might be caused by a relative decrease in other bacteria due to prophylactic antibiotic administration rather than an absolute increase.

Effect of Chemotherapy on the Gut Microbiome of Breast Cancer Patients During the First Year of Treatment

“…In a Dutch study, baseline gut microbiome Shannon index was 5% higher among breast cancer patients in the neoADJ (n = 18) than those in ADJ (n = 63) groups ( p = 0.057). 8 In contrast, baseline alpha diversity measures in our study were lower in the neoADJ than ADJ group ( Table 2 ) but the ADJ group in the previous study was ~5 times larger while the sample size of the neoADJ in the two studies were similar. A second study based on the CANTO cohort collected fecal samples before (n = 76) and after (n = 45) chemotherapy from breast cancer patients and performed analyses combining the neoADJ and ADJ groups 16 .…”

“…Levels of several taxa (e.g., Ruminococcaceae, Christensellaceae, unclassified Enterobacterales) decreased after completion of chemotherapy while levels of Lactobacillus increased. 8 , 15 However, among breast cancer patients from the CANTO (CANcer Toxicities) cohort with paired samples before and after chemotherapy (35 ADJ, 10 neoADJ), alpha diversity measures increased after chemotherapy compared to before chemotherapy ( p = 0.033). There was a shift of the microbiome composition towards increases in Methanobacteria species and reductions in the abundance of species such as Veillonella that have been associated with worse prognosis.…”

The Link Between the Microbiota and HER2+ Breast Cancer: The New Challenge of Precision Medicine

“…The number of studies on the differences between the gut microbiota of patients and healthy women has been increasing (8)(9)(10)(11)(12), and despite the discrepancies in identified microbial taxa between them, most studies have reported reduced a-diversity in the gut microbiota of women with BC (8,9,12,13). Notably, Zitvogel and colleagues showed that the fecal microbiota composition discriminates groups of patients by tumor size (< or >pT1), grade (G1 and 2 vs G3), axillary node involvement (Nvs N+), and TNM stage (stage I vs stage II/III) (14).…”

L-norvaline affects the proliferation of breast cancer cells based on the microbiome and metabolome analysis

“…Moreover, the gut microbiota might be the dominant mediator of cancer treatment response (Laborda‐Illanes et al, 2020). In the adjuvant treatment of breast cancer, the use of antibiotics could lead to changes in relative microbiota abundance in patients (Aarnoutse et al, 2021). Thus, the study of gut microbiota in breast cancer was necessary.…”