This study investigates the intrinsic resistance of tumorigenic breast cancer cells to chemotherapy and the potential of lapatinib, an EGFR/HER2 pathway inhibitor, to target these cells. The researchers analyzed paired breast cancer biopsies from patients before and after neoadjuvant chemotherapy (for HER2-negative tumors) or lapatinib treatment (for HER2-positive tumors). They found that chemotherapy increased the percentage of CD44+/CD24-low cells, which are known to be resistant to chemotherapy and responsible for cancer relapse, and enhanced their ability to form mammospheres in vitro. In contrast, lapatinib treatment did not significantly reduce the percentage of these cells but showed a non-statistically significant decrease in their self-renewal capacity. The study suggests that combining lapatinib with conventional therapy may be a promising strategy to eliminate these chemotherapy-resistant cells and improve long-term survival.This study investigates the intrinsic resistance of tumorigenic breast cancer cells to chemotherapy and the potential of lapatinib, an EGFR/HER2 pathway inhibitor, to target these cells. The researchers analyzed paired breast cancer biopsies from patients before and after neoadjuvant chemotherapy (for HER2-negative tumors) or lapatinib treatment (for HER2-positive tumors). They found that chemotherapy increased the percentage of CD44+/CD24-low cells, which are known to be resistant to chemotherapy and responsible for cancer relapse, and enhanced their ability to form mammospheres in vitro. In contrast, lapatinib treatment did not significantly reduce the percentage of these cells but showed a non-statistically significant decrease in their self-renewal capacity. The study suggests that combining lapatinib with conventional therapy may be a promising strategy to eliminate these chemotherapy-resistant cells and improve long-term survival.