During the PEG tube insertion procedure, a firm, friable nodule approximately 1-2 cm was noted in the anterior

proximal gastric antrum, and a biopsy was taken for further study. The new biopsy revealed an adenocarcinoma, consistent with primary tumor. However, in contrast to the initial negative result, HER2 was found to be read more amplified (Clarient, Figure 1A). In view of the discrepancy of the HER2 results, repeat testing of the initial tumor block was ordered and the HER2 study was carried Inhibitors,research,lifescience,medical out on 3 different areas by the same laboratory that had performed the initial testing. Surprisingly, it showed contradictory results with one of three areas exhibiting HER2 amplification (Figure 1B), while no amplification was noted in the other two areas, consistent with the original diagnosis (Figure 1C, D). Given the positive outcomes experienced by patients exhibiting HER2 positive expression in the the recent ToGA study, addition Inhibitors,research,lifescience,medical of trastuzumab treatment was planned for the subsequent chemotherapy cycle. Unfortunately, the patient died before he could be started on trastuzumab therapy. Figure 1 A. Gastric Nodule Biopsy (9/16/2011): HER2/neu by Fluorescence in Situ Hybridization HER2/CEP17 Ratio 3.0, Amplified; B. Esophageal Mass Biopsy (4/11/2011) HER2/neu by Fluorescence in Situ Hybridization HER2/CEP17 Inhibitors,research,lifescience,medical Ratio Inhibitors,research,lifescience,medical 2.5, Amplified; C. Esophageal

Mass … Discussion Treatment of metastatic gastroesophageal cancer remains very challenging despite the recent use of various combinations of chemotherapeutic agents. For example, in the pivotal phase 3 REAL-2 study, no significant advantage was found among four different three-drug combination regimens that were assessed, with a comparable median overall survival, reported between 9 to 11 months for all regimens (3).

Approximately 24% of gastroesophageal adenocarcinomas (GE-AC) Nintedanib msds overexpress HER2. HER2 overexpression in GE-AC has been associated with more aggressive biological behavior Inhibitors,research,lifescience,medical and poor outcome, but has not been associated with gender or age at time of diagnosis (8). Chemotherapy in combination with trastuzumab prolonged the median overall survival of gastroesophageal cancer Entinostat significantly to 13.8 months, and higher expression of HER2 was predicted to confer a better prognosis, extending mean overall survival from under 12 months to approximately 16 months (7). Combination of trastuzumab and chemotherapy represents a new standard of care in HER2 positive gastroesophageal cancer. It is predictable that the anti-HER2 pathway will play a more important role in the foreseeable future with the introduction of new agents such as lapatinib or pertuzumab. It is well known that HER2 positive breast cancer can become HER2 negative following treatment with trastuzumab (9).