Changes in intestinal microbiota in postmenopausal oestrogen receptor-positive breast cancer patients treated with (neo)adjuvant chemotherapy

Abstract

This clinical study explored the associations between the intestinal microbiota, chemotherapy toxicity, and treatment response in postmenopausal oestrogen receptor positive breast cancer patients.Oestrogen receptor positive postmenopausal breast cancer patients were prospectively enroled in a multicentre cohort study and treated with 4 cycles of (neo)adjuvant adriamycin, cyclophosphamide (AC) followed by 4 cycles of docetaxel (D). Patients collected a faecal sample and completed a questionnaire before treatment, during AC, during D, and after completing AC-D. Chemotherapy toxicity and tumour response were determined. Intestinal microbiota was analysed by amplicon sequencing of the 16 S rRNA V4 gene-region. In total, 44 patients, including 18 neoadjuvant patients, were included, and 153 faecal samples were collected before AC-D (n = 44), during AC (n = 43), during D (n = 29), and after AC-D treatment (n = 37), 28 participants provided all four samples. In the whole group, observed species richness reduced during treatment (p = 0.042). The abundance of Proteobacteria, unclassified Enterobacterales, Lactobacillus, Ruminococcaceae NK4A214 group, Marvinbryantia, Christensenellaceae R7 group, and Ruminococcaceae UCG-005 changed significantly over time. Patients with any grade diarrhoea during docetaxel treatment had a significantly lower observed species richness compared to patients without diarrhoea. In the small group neoadjuvant treated patients, pathologic response was unrelated to baseline intestinal microbiota richness, diversity and composition. While the baseline microbiota was not predictive for pathologic response in a rather small group of neoadjuvant treated patients in our study, subsequent shifts in microbial richness, as well as the abundance of specific bacterial taxa, were observed during AC-D treatment in the whole group and the neoadjuvant group.

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

“…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 . In the Dutch study, alpha diversity decreased after completion of chemotherapy (observed species decreased 9.6% [ p = 0.042] and Shannon index decrease 2.5% [p = 0.21]) 15 whereas in the CANTO study, species richness increased ( p = 0.033) after completion of chemotherapy (p = 0.033). 16 However, because these two previous studies did not investigate changes in alpha diversity separately by type of chemotherapy and our results suggest increased in alpha diversity in the neoADJ group but decreases in the AD group, additional studies by type of chemotherapy will be needed.…”

“…It should be noted that the last fecal sample was collected ~100 days after completion of chemotherapy in our study but it is not clear when the fecal sample was collected after completion in the previous two studies. 15 , 16 It is reasonable to speculate that changes in the gut microbiome immediately after completion of chemotherapy may differ from gut microbiome assessed a few months after completion of chemotherapy. A third study included 24 breast cancer patients with HER2+ disease who received neoADJ trastuzumab-based chemotherapy.…”

“…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.…”

Counteracting gemcitabine+nab-paclitaxel induced dysbiosis in KRAS wild type and KRASG12D mutated pancreatic cancer in vivo model

“…Finally, since we observed that gemcitabine alone [10,30] or combined with nab-paclitaxel, affects gut microbiota in mouse models of PDAC and since it was reported that chemotherapy reshapes the gut microbiota in human patients suffering from different types of cancers [31][32][33][34], often promoting an overgrowth of inflammatory Proteobacteria [31,33], we plan to investigate, in the next future, the microbiota composition of PDAC patients before and after receiving chemotherapy.…”

Preliminary Analysis of Gut Microbiome and Gastrointestinal Symptom Burden in Breast Cancer Patients Receiving Chemotherapy Compared to Healthy Controls

“…These microbial changes can in turn influence the presence and severity of GI symptoms. Aarnoutse et al (2022) collected stool samples and symptom data from post-menopausal breast cancer patients receiving neoadjuvant Adriamycin, Cyclophosphamide, and Docetaxel chemotherapy. They found that patients reporting diarrhea during treatment had a significantly lower observed species richness compared to patients who did not have diarrhea during treatment.…”