1Department of Oncology, Tobruk Medical Center, Libya 2Department of Medicine, University of Tobruk, LibyaFulltext PDF
Human Epidermal Growth Factor Receptor 2 (HER2) positive breast cancer patients carry a high risk of recurrence. Moreover, patients who didn’t achieve pathological Complete Response (pCR) after Neoadjuvant Therapy (NAT) have a higher risk of relapse than those who did. KATHERINE trial was addressing that group of patients who were HER2 positive early breast cancer, and had the Residual Invasive Disease (RID) after NAT. In the trial, patients were randomized in two groups and assigned to receive adjuvant therapy, either trastuzumab-emtansine (T-DM1), or trastuzumab, and the primary end point was invasive Disease-Free Survival (DFS). The investigators of the trial concluded there was a 50% reduction in recurrence and death with adjuvant T-DM1 in comparison to adjuvant trastuzumab alone. However, the trial was designed to assess HER2 status on pretreatment biopsies rather than postoperative samples, and not considering the discordance in HER2 status between the two samples, bearing in mind, HER2-loss after NAT has been frequently reported phenomenon, which could be due to either heterogeneity of the tumor or false positive result of the HER2 expression status testing of the primary tumor sample. Heterogeneity is a sign of aggressiveness of the tumor, and false positive HER2-overexpression would lead to an irrelevant and an ineffectual therapy. Concordantly, a considerable number of studies concluded that, patients with HER2-loss had shorter DFS. Therefore, HER2-loss should have been considered a confounding factor, and patients who manifested loss of HER2 amplification should have been distributed equally between the two arms of the trial to eliminate bias.
HER2-loss after neoadjuvant therapy; Discrepancy in HER2 expression; Trastuzumab; T-DM1; HER2+ Early breast cancer
Elmahdi-Omran K. Trastuzumab Emtansine for Residual Invasive HER2- Positive Breast Cancer: A Critical Review. Clin Oncol. 2020; 5: 1743.