Patient-derived xenograft models of primary breast cancer for preclinical evaluation of neoadjuvant therapies.

Abstract

Targeted therapies are important for invasive breast cancer (IBC) treatment but are generally not standard of care in the neoadjuvant setting. To identify therapies with the potential to improve neoadjuvant treatment response, it is essential to develop patient-derived preclinical models that faithfully reflect the diversity of primary IBC subtypes in patients. Here, we generated and characterized a large-scale cohort of 60 mouse-intraductal patient-derived xenograft (MIND-PDX) models representing all subtypes of primary IBC, as well as seven matched PDX-derived organoids. We showed that our IBC-MIND cohort can serve as a platform for preclinical evaluation of experimental neoadjuvant treatments. For triple-negative IBC, we demonstrated that neoadjuvant treatment does not benefit from addition of a PARP inhibitor, whereas for estrogen receptor-positive IBC, the combination of a CDK4/6 inhibitor and fulvestrant improved neoadjuvant treatment response. Our work provides a valuable resource of primary IBC models to study breast cancer biology and develop neoadjuvant treatments.