Loss of HER2 in previously HER2-positive breast tumors is not rare, occurring in up to 50% of breast cancers;however, clinical research and practice underestimate this issue. Many studies have reported the loss of HER...Loss of HER2 in previously HER2-positive breast tumors is not rare, occurring in up to 50% of breast cancers;however, clinical research and practice underestimate this issue. Many studies have reported the loss of HER2 afterneoadjuvant therapy and at metastatic relapse and identified clinicopathological variables more frequentlyassociated with this event. Nevertheless, the biological mechanisms underlying HER2 loss are still poorlyunderstood. HER2 downregulation, intratumoral heterogeneity, clonal selection, and true subtype switch have beensuggested as potential causes of HER2 loss, but translational studies specifically investigating the biology behindHER2 loss are virtually absent. On the other side, technical pitfalls may justify HER2 loss in some of these samples.The best treatment strategy for patients with HER2 loss is currently unknown. Considering the prevalence of thisphenomenon and its apparent correlation with worse outcomes, we believe that correlative studies specificallyaddressing HER2 loss are warranted.展开更多
文摘Loss of HER2 in previously HER2-positive breast tumors is not rare, occurring in up to 50% of breast cancers;however, clinical research and practice underestimate this issue. Many studies have reported the loss of HER2 afterneoadjuvant therapy and at metastatic relapse and identified clinicopathological variables more frequentlyassociated with this event. Nevertheless, the biological mechanisms underlying HER2 loss are still poorlyunderstood. HER2 downregulation, intratumoral heterogeneity, clonal selection, and true subtype switch have beensuggested as potential causes of HER2 loss, but translational studies specifically investigating the biology behindHER2 loss are virtually absent. On the other side, technical pitfalls may justify HER2 loss in some of these samples.The best treatment strategy for patients with HER2 loss is currently unknown. Considering the prevalence of thisphenomenon and its apparent correlation with worse outcomes, we believe that correlative studies specificallyaddressing HER2 loss are warranted.