The impact of neoadjuvant chemotherapy (NAC) ± anti-HER2 antibodies (mAbs) on gut microbiome composition in early breast cancer (EBC): A pilot prospective study.

Abstract

e12626 Background: Gut microbiome composition and its changes induced by chemotherapy ± anti-HER2 monoclonal antibodies (mAbs) in breast cancer patients are poorly recognized. We assessed gut microbiome composition before and after NAC ± anti-HER2 mAbs in early breast cancer (EBC). Methods: Stool samples were collected by patients at home using a collection kit (OMR-200 (Diversigen). Samples were extracted using the Qiagen PowerSoil Pro kit. Paired-end whole-genome shotgun sequencing was performed to a depth of at least 2M reads per sample. Bacteria were identified from the sequences using the Cmbio HUB Kepler pipeline. Community differences by treatment group were analyzed by calculating alpha and beta diversity indices along with differential abundance and regression analysis using the tool MaAsLin2. Chi-square, Fisher’s exact test, and Wilcoxon rank-sum tests were used to compare demographic variables (age, diet, use of probiotics and/or antibiotics before and during chemotherapy, granulocyte growth factors for prophylaxis and in case of neutropenic fever, gastrointestinal symptoms during therapy). Results: We analyzed 55 samples from 29 Caucasian patients (mean age of 53 years, range 31–81), including luminal HER2-positive (n = 3), non-luminal HER2-positive (n = 9), triple negative (n = 10), and luminal HER2-negative (n = 7) cases. 26 samples paired before and after neoadjuvant therapy: included 11 NAC + anti-HER2 mAbs: AC/PHPXL (doxorubicin (A), cyclophosphamide (C), pertuzumab (P), trastuzumab (H), paclitaxel (PXL), P/H/PXL and carboplatin (CARB) and 15 NAC alone: AC followed by PXL ± CARB. All regiments with standard premedication with steroids and ondansetron. We excluded 3 patients who received pembrolizumab from the analysis. In patients administered NAC alone, no significant differences were found between alpha and beta diversity and their relation with pathological complete (pCR) or non-complete response (non-pCR). In turn, NAC + anti HER2 mAbs induced changes in microbiome composition, which were related with response: Actinomycetota showed a correlation with pCR (false discovery rate , FDR 2.110e−01; coefficient: 2.14e+00; p = 0.023) and Methanobacteriota with non-pCR (FDR 2.110e−01; coefficient: −6.02e−01; p = 0.021). Increased abundance of Coprococcus eutactus was associated with non-pCR (FDR: 2.528e-03 ratio: -3.77e+00; p = 0.002). Conclusions: Our data show that NAC + mAbs, as opposed to NAC alone, impacts the composition of the microbiome, which correlates with pathological response. Coprococcus eutactus increased abundance in HER2-positive EBC patients with non-pCR after NAC + anti HER2 mAbs needs further investigation.