Clinical trials have reported lower pCR rates in patients with HR+/HER2+ breast cancer compared to those with HR−/HER2+ breast cancer.5,6,20,33–35 Due to the multi-target co-regulatory properties of HR+/HER2+ breast cancer, the inhibition of multiple signaling pathways has proven effective in preventing cross-resistance between therapies. The gene discussed is ERBB2; the disease is breast cancer.