Enrichment of intestinal bifidobacterium genus is associated with residual disease among patients with early-stage HER2+ breast cancer (BC) following neoadjuvant chemotherapy (NACT)

Abstract

Objective: The objective of this study was to characterize the gut microbiome (GM) of patients with early-stage breast cancer (eBC) who underwent NACT and to evaluate its association with clinicopathological factors and outcomes.
Methodology: This was a prospective study conducted at two Brazilian Institutions. Fecal samples were collected at the
baseline and prior to surgery. The GM was analyzed by 16S rRNA amplicon sequencing to characterize the alpha (InvSimpson
indexes) and beta (weighted UniFrac distance) diversity, as well as the taxonomic composition. Results: Among the 55
female patients included, the median age was 49 years, 56% had stage III disease, and 23% had used antibiotics in the
prior 2 months before starting NACT. Regarding the immunohistochemical profile, 34.5% (n=19) of patients had estrogen
receptor-positive (ER+)/HER2-negative BC, 20% (n=11) had HER2-positive disease, and 45.5% (n=25) were triple-negative.
All patients with ER+ had KI 67 >14%. There was no significant difference in alpha or beta-diversity between patients
with or without pathological complete response, nor within clinical pathologic factors. The taxonomic profiling of fecal
samples revealed that Lachnospiraceae at family and Blautia at genus levels were the most abundant taxon, and longitudinal samples collected during NACT showed no significant changes in GM composition. We found an enrichment for
Clostridia sp. among patients who did not use antibiotics (p<0.05, pFDR≤0.25). Notably, we found a higher abundance of
Bifidobacterium genus (p<0.05, pFDR≤0.25) in baseline samples from patients with HER2+ tumors who presented residual disease following NACT. Conclusion: This pilot study demonstrates the feasibility of GM sequencing in patients
with eBC. We identified a significant association between the relative abundance of intestinal Bifidobacterium genus response to NACT among patients with HER2+ tumors. If validated, these results can help tailor the preoperative systemic
treatment of patients with HER2+ eBC.