Antibiotic use and survival from breast cancer

Background Recent studies in multiple breast cancer mouse models have found that antibiotics, by altering the gut microbiota, can accelerate tumour growth.

In humans, a recent cohort study restricted to triple negative breast cancer showed that breast cancer patients using a greater number of antibiotics had markedly worse survival. These studies have raised concern about the implications of repeated antibiotic use in breast cancer patients.

Aims To determine whether breast cancer patients who frequently use oral antibiotics have increased risk of breast cancer-specific mortality.

Methods A cohort of over 100,000 women newly diagnosed (from 1998 to 2017) with stage 1 to 3 breast cancer will be identified from cancer registry records from England, Wales and Scotland. The primary outcome will be breast cancer-specific mortality identified from national mortality records up to 2021.

Oral antibiotic use will be ascertained from electronic GP prescribing records (from QResearch in England and SAIL Databank in Wales) or dispensing records (from the Prescribing Information System in Scotland).

Time-dependent cox regression models will be used to calculate hazard ratios (HR) and 95% confidence intervals (95% CIs) for breast cancer-specific mortality in antibiotic users compared with non-users after cancer diagnosis (with antibiotic use modelled as a time varying covariate).

Adjusted HRs and 95% CIs will be calculated including in the model: age, year, stage, grade, surgery, radiotherapy, chemotherapy, hormone therapy use (including tamoxifen and aromatase inhibitors), comorbidities, medication use, deprivation and smoking status. The main analysis will focus upon the class of antibiotic and duration of use.

A separate analysis will be conducted investigating the impact of antibiotic use immediately before breast cancer diagnosis, during cancer development, on cancer-specific mortality.

How the results of this research will be used Our study could provide evidence that breast cancer patients who frequently use oral antibiotics, or a specific class of antibiotics, have reduced survival.

This would (a) inform antibiotic practice, specifically supporting more prudent prescribing of antibiotics in breast cancer patients such as delaying prescriptions in typically self-limiting infections, using narrow-spectrum antibiotics and shortening treatment duration where possible; and (b) provide insight into underlying cancer mechanisms.

Alternatively, our study could show no evidence of a reduction in survival in breast cancer patients frequently using antibiotics and hence provide reassurance to patients and GPs of the safety of antibiotics in these patients.