The Long and Winding Road toward Prevention of Estrogen Receptor–Negative and BRCA1-Associated Breast Cancer

Although endocrine prevention has proven to be successful in reducing estrogen receptor (ER)-positive breast cancer, there is still no pharmacologic strategy for preventing ER-negative and BRCA1-associated disease. The study by Moyer and colleagues demonstrated that RXR agonists, particularly IRX4204, delay tumor onset in BRCA1-deficient and triple-negative mouse models, suggesting a potential preventive role through immunomodulation. Yet the translational road ahead is complex, limited by biological uncertainty, sociocultural barriers, and safety concerns. A rational next step may be to carefully design window-of-opportunity trials in BRCA1 carriers undergoing risk-reducing bilateral mastectomy to assess biomarker modulation and tolerability. See related article by Moyer et al., p. 161.