Understanding how antibiotic-induced microbiota disturbances affect breast cancer progression (360G-Wellcome-211611_Z_18_Z)

Breast cancer (BC) is the biggest cancer killer for UK women, with ~12,000 deaths/annum. Critically, incidence has risen by 20% over the last 20 years, and treatment for BC, particularly metastatic disease, remains challenging. Recently, the gut-tumour axis has emerged as an important modulator of anti- cancer immune responses, which is correlated with the ability of gut microbes (i.e. the microbiota) to impact mucosal and systemic immunity. Whilst previous studies have focussed on how specific microbes augment immune checkpoint drugs in non-BC cancers, there remains an important open question; what are the consequences for disruption of the microbiota (e.g. antibiotics) on primary and metastatic BC? Clinically this is highly pertinent as previous population studies have correlated antibiotic usage with increased incidence of BC, and BC patients also receive antibiotics throughout treatment. Our preliminary data shows in disease relevant mouse models that a harsh cocktail of antibiotics (which severely disrupts the microbiota) promotes primary tumour growth, and metastatic spread, and that this correlates with immune readouts known to correlate with poor BC prognoses. This summer studentship will examine how clinically-relevant antibiotic regimes (which generate less severe microbiota disturbances) impact BC progression, and tumour immune surveillance.