The gut microbiome and response to neoadjuvant chemotherapy in breast cancer


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Kirsty Ross1,Rodanthi Papadopoulou2,Ben Nichols2,Martin Macleod1,Judith Fraser1,Sophie Barrett1,Jeff Evans2,Konstantinos Gerasimidis2,Iain Macpherson3
1Beatson West of Scotland Cancer Centre, Glasgow, UK,2University of Glasgow, Glasgow, UK,3Beatson West of Scotland Cancer Centre, Glasgow, UK, University of Glasgow, Glasgow, UK

Abstract

Background

Pre-clinical data suggest that the activity of cytotoxic chemotherapy may be dictated by the gut microbiome. Pathological complete response (pCR) to neoadjuvant chemotherapy (NACT) predicts improved event-free and overall survival in patients with all breast cancer subtypes. This prospective study investigates the compositional and functional changes in the gut microbiome during NACT and explores correlations with pathological response.

Method

Female patients receiving NACT for breast cancer at the BWoSCC were enrolled from Aug2017-Mar2019. Stool samples were collected at 3 timepoints: 1) before 1st cycle NACT, 2) during NACT, 3) after final cycle of NACT. DNA was extracted and the V4 region of the 16S rRNA gene was amplified for 2x250 bp next-generation sequencing. After surgery each patient’s response was categorised as pCR (ypT0/is ypN0) or non-pCR.

Results

To date 21 patients have been recruited (18 currently evaluable.) Median age and BMI were 56 (range 33-72) and 28.6 kg/m2(range 19.6-55.6) respectively. Most (n=9, 42.9%) had HER2+ cancers whilst 8 (38.1%) had TNBC and 4 (19%) had (ER+HER2-). NACT included FEC-T in 9 (42.9%), FEC-TH in 6 (28.6%) and other regimes in 6 (28.6%). pCR was observed in 4 of 18 evaluable patients (22.2%.) Taxonomic richness was non-significantly higher in responders vs. non-responders at timepoints; 1) mean 515 vs. 367; p = 0.059, 2) mean 496 vs. 330; p = 0.061 and 3) mean 548 vs. 293; p = 0.069. In patients with 3 timepoint samples available (n=5), lack of response was associated with an increasing proportional abundance of Bacteroides, after completion of NACT (mean 0.57 vs. 0.13; p=0.038.)

Conclusion

Early data demonstrate non-significant trends in compositional differences in the gut microbiome structure of patients with pCR versus non-pCR. These include lower richness and higher proportional abundance of Bacteroides in the non-pCR group.