Antibiotics modulate neoadjuvant therapy efficiency in patients with breast cancer: a pilot analysis

Abstract

Mounting evidence suggests that microbiota dysbiosis caused by antibiotic administration is a risk factor for cancer, but few research reports focus on the relationships between antibiotics and chemotherapy efficiency. We evaluated the influence of antibiotic administration on neoadjuvant therapy efficacy in patients with breast cancer (BC) in the present study. BC patients were stratified into two groups: antibiotic-treated and control based on antibiotic administration within 30 days after neoadjuvant therapy initiation. Disease-free survival (DFS) and overall survival (OS) were assessed using the Kaplan-Meier method, and the Cox proportional hazards model was used for multivariate analyses. The pathologic complete response rate of the control group was significantly higher than that of the antibiotic-treated group (29.09% vs. 10.20%, p = 0.017). Further univariate analysis with Kaplan-Meier calculations demonstrated that antibiotic administration was strongly linked with both reduced DFS (p = 0.04) at significant statistical levels and OS (p = 0.088) at borderline statistical levels. Antibiotic administration was identified as a significant independent prognostic factor for DFS [hazard ratio (HR) 3.026, 95%, confidence interval (CI) 1.314-6.969, p = 0.009] and OS (HR 2.836, 95% CI 1.016-7.858, p = 0.047) by Cox proportional hazards model analysis. Antibiotics that initiated reduced efficiency of chemotherapy were more noticeable in the HER2-positive subgroup for both DFS (HR 5.51, 95% CI 1.77-17.2, p = 0.003) and OS (HR 7.0395% CI 1.94-25.53, p = 0.003), as well as in the T3-4 subgroup for both DFS (HR 20.36, 95% CI 2.41-172.07, p = 0.006) and OS (HR 13.45, 95% CI 1.39-130.08, p = 0.025) by stratified analysis. Antibiotic administration might be associated with reduced efficacy of neoadjuvant therapy and poor prognosis in BC patients. As a preliminary study, our research made preparations for further understanding and large-scale analyses of the impact of antibiotics on the efficacy of neoadjuvant therapy.

Figure 1

Comparison of dose intensity and frequency of dose delay. (A) The mean dose intensity. (B) frequency of dose delay.

Figure 2

The impact of antibiotic administration on the clinical outcome and efficacy of BC patients. (A) Miller-Payne grade in BC patients. (B) Analysis of the pathological complete response (pCR) rate in BC patients. (C) The Kaplan–Meier curve of progression-free survival (DFS). (D) The Kaplan–Meier curve of overall survival (OS).

Figure 3

Subgroup analyses of independent prognostic factors for DFS (A) and OS (B).