Abstract
Simple SummaryBesides the already known factors that increase the risk of breast cancer, like hormonal treatment, heredity, and obesity, growing evidence exists that intestinal microbiota can influence breast cancer carcinogenesis. Current clinical information into the role of the intestinal microbiota in breast cancer patients is limited. This study aimed to see whether there are differences in intestinal microbiota richness, diversity, and composition between oestrogen receptor positive breast cancer patients and controls. We concluded that the intestinal microbiota richness, diversity, and composition were not different between breast cancer patients and postmenopausal controls. An 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 surgery associated factors rather than an absolute increase. For future studies, we strongly advise a more homogeneous group of breast cancer patients of preferably treatment-naive patients.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.
Highlights
IntroductionBreast cancer is the most common cancer in women worldwide [1]. In the Netherlands, approximately one out of seven women (15%) will develop breast cancer during their lifetime [2]
Contaminated Amplicon sequence variants (ASVs) identified by decontam [25] were filtered out together with ASVs presented in less than 5%
To correct for the potential confounding effect of prophylactic antibiotic use in patients scheduled for adjuvant treatment, we repeated the PERMANOVA analysis upon the exclusion of patients that used prophylactic antibiotics. This additional sensitivity analysis indicated no differences in microbial community structure between patients scheduled for neoadjuvant systemic treatment (n = 18), adjuvant systemic treatment (n = 31), and controls (n = 67) at the phylum (p = 0.471) and genus levels (p = 0.124)
Summary
Breast cancer is the most common cancer in women worldwide [1]. In the Netherlands, approximately one out of seven women (15%) will develop breast cancer during their lifetime [2]. A combination of genetic, epigenetic, and environmental factors are known to contribute to the development of cancer [3] Factors such as hormonal treatment, heredity, and obesity are known to increase the risk of breast cancer [4,5]. Still, other factors, such as intestinal microbiota, are thought to influence breast cancer carcinogenesis [4,6,7]. There has been a growing interest in the role of the human intestinal microbiota and the development of cancer. Environmental factors and host genetic factors both influence microbiota diversity and composition and can generate dysbiosis leading to a disturbed metabolism and even carcinogenesis [10,11]. Growing evidence exists that intestinal microbiota can influence breast cancer carcinogenesis.
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