Abstract
Human epidermal growth factor receptor 2 (HER2) is involved in the pathogenesis and poor outcomes of several types of cancer, including advanced gastric and gastroesophageal junction cancer. Molecular-targeted drugs, such as trastuzumab, which prolong overall survival and progression-free survival in HER2-positive breast cancer, may also be beneficial in patients with HER2-positive gastric cancer. Several studies have examined this possibility, such as the Trastuzumab for Gastric Cancer trial. In this context, the first part of this review provides an update on our knowledge of HER2 in breast and gastric cancer, including the detection and prognostic relevance of HER2 in gastric cancer. The second part of the review discusses the results of pivotal clinical trials that examined the potential for using trastuzumab to treat this disease. This section also summarizes the trials that have been conducted or that are underway to determine the optimal uses of trastuzumab in gastric cancer, including its use as monotherapy and continuation beyond disease progression. The final section discusses the future prospects of other anti-HER2 drugs, including lapatinib, trastuzumab emtansine, and pertuzumab, for the treatment of HER2-positive gastric cancer. The introduction of trastuzumab led to the establishment of a new disease entity, “HER2-positive gastric cancer,” similar to HER2-positive breast cancer. It is expected that more anti-HER2 drugs will be developed and introduced into clinical practice to treat HER2-positive cancers, including gastric cancer.
Highlights
Up to 30 % of breast cancers overexpress human epidermal growth factor receptor 2 (HER2, c-erbB2), and Human epidermal growth factor receptor 2 (HER2) positivity is associated with significantly worse outcomes than HER2-negative breast cancer [1]
The results of this study showed that trastuzumab in combination with chemotherapy significantly improved overall survival in patients with HER2-positive advanced gastric or gastroesophageal cancer compared with chemotherapy alone, and this improvement was significant in patients with high HER2 expression
Based on our increasing knowledge of the role for HER2 in gastric cancer, other agents targeting HER2 are being developed for use in this setting, including lapatinib [66, 67]
Summary
Up to 30 % of breast cancers overexpress human epidermal growth factor receptor 2 (HER2, c-erbB2), and HER2 positivity is associated with significantly worse outcomes than HER2-negative breast cancer [1]. Trastuzumab, a monoclonal antibody directed against HER2, was one of the first molecular-targeted drugs to be developed and was originally introduced for the treatment of HER2-positive metastatic breast cancer. Its approval in this setting was based on two pivotal studies, which showed the efficacy of trastuzumab administered with paclitaxel [2] or trastuzumab alone as first-line therapy [3]. Trastuzumab has revolutionized the treatment of HER2positive breast cancer and improved its outcomes [10] Based on these findings, trastuzumab is considered a key drug for treating HER2-positive breast cancer, which has been established as a major disease subtype of breast cancer
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