The mechanism study revealed that FLU inhibited the HER2 pathway in both trastuzumab-sensitive and trastuzumab-resistant HER2-positive breast cancer cells by decreasing the levels of the truncated p95HER2, phospho-HER2, phospho HER3, and phospho-Akt, and preventing the hetero-dimerization of HER2/HER3. The gene discussed is ERBB2; the disease is breast cancer.