The challenges of modeling hormone receptor-positive breast cancer in mice

Estrogen receptor-positive (ER+) tumors account for 70-80% of all breast cancer (BC) cases and are characterized by estrogen dependency for their growth. Endocrine therapies using estrogen receptor antagonists or aromatase inhibitors represent a key component of the standard of care for these tumors. The occurrence of de novo or acquired resistance to estrogen withdrawal represents an important clinical problem, impacting on patient survival. In addition, despite an initially favorable outcome, a part of ER+ BC patients present with disease recurrence locally or at distant sites years or even decades after apparent remission. In vivo models that closely mimic human disease are urgently needed to study the biology of these tumors, investigate the molecular mechanisms underlying endocrine resistance and identify patients at risk of recurrence. Despite the similarities in the overall hormonal regulation of mammary gland development between mice and humans, the majority of the mammary carcinomas occurring in genetically engineered mouse models (GEMMs) are ER negative and most xenograft models are based on few ER+ cancer cell lines. We recently showed that the microenvironment is critical for ER+ cancer cells and discuss in this review the potential of intraductal xenograft model for basic and preclinical research.