Clinicopathologic factors associated with HER2‐positive gastric cancer and its impact on survival outcomes—A systematic review

Abstract

With the availability of a therapeutic target and an effective agent in trastuzumab, a systematic examination of the literature to investigate the role of human epidermal growth factor 2 (HER2) as a prognostic factor for survival and its association with clinicopathologic markers may improve treatment. An electronic search of the MEDLINE and PubMed databases (January 1990 to January 2011) was undertaken to identify translational studies that correlated HER2 with clinicopathologic markers and/or survival outcome. This review included 49 studies totaling 11,337 patients. Forty-four percent of patients had Stage I/II, and 56% had Stage III/IV disease. Immunohistochemistry was most commonly used to assess HER2 expression, identifying a median rate of 18% (range, 4-53%) of gastric cancer demonstrating HER2 overexpression. In patients with and without HER2 overexpression, the median 3-year disease-free survival rate was 58% (range, 50-88%) and 86% (range, 62-97%), respectively. Of the 35 studies reporting the impact of HER2 overexpression on survival, 20 studies (57%) reported no difference in overall survival, two studies (6%) reported significantly longer overall survival in patients with HER2 overexpression and 13 studies (37%) reported significantly poorer overall survival in patients with HER2 overexpression. The median overall survival and 5-year survival rate was 21 (range, 10-57) months and 42%, and 33 (range, 13-80) months and 52% in patients with and without HER2 overexpression, respectively. HER2 overexpression appears to be associated with poorer survival and with intestinal-type gastric cancer in this group of patients for whom majority undergone curative gastrectomy.On a global scale, gastric cancer remains the second most common cause of cancer-related death with an estimated 930,000 new cases diagnosed each year albeit an overall decline in incidence. 1 Noncardia gastric cancers have steadily declined. However, it has been observed that proximal gastric cancers (cardia and oesophago-gastric tumors) are increasing at a rate of up to 10% per year, far exceeding that of any other type of cancer. Metastatic or advanced unresectable gastric cancer is an aggressive malignancy with a poor prognosis despite chemotherapy treatment with median survival of 7.5 to 12 months and a median survival of 3 to 5 months if managed by best supportive care. 2 Gastric cancer is a chemosensitive disease where a range of chemotherapy agents may achieve response rates of 30 to 40%; however, in the advanced setting, the disease is limited by a low complete response rate and the response duration is protracted often leading to disease progression and treatment related toxicities. 3 Combination chemotherapy with a Japanese standard doublet of fluoropyrimidine and platinum or western triplet regimens has shown better response rates and outcomes over single agent chemotherapy. However, there remains no established global standard for treatment.The human epidermal growth factor 2 (HER2) gene is a proto-oncogene where high amplifica...

Assessment of HER2 status in patients with gastroesophageal adenocarcinoma treated with epirubicin-based chemotherapy: heterogeneity-related issues and prognostic implications

“…However, on the basis of Chua and Merret's report [12], despite the relatively small size of this retrospective cohort, we might speculate that the longer survival observed among HER2-positive patients might mirror a benefit from anthracycline-based chemotherapy rather than a prognostic effect of the biomarker itself.…”

“…A systematic review of the literature found that, among 35 published studies from 2000 to 2011, 20 (57 %) reported no difference in OS, 2 (6 %) reported significantly longer OS, and 13 studies (37 %) reported significantly poorer OS in patients with HER2 overexpression [12]. More recently, retrospective analyses did not detect survival differences according to HER2 status in three large randomized phase III trials for early-stage disease [25][26][27], as well as in the metastatic disease setting [28].…”

“…Unlike breast cancer, the value of HER2 positivity in gastroesophageal adenocarcinomas as a predictive marker for anthracycline sensitivity has never been demonstrated, while its prognostic value remains unclear with inconsistent findings across different series [12]. On the other hand, assessment of HER2 expression by immunohistochemistry (IHC) is possibly challenged by a substantial heterogeneity of HER2 staining [13][14][15][16], which carries an inherent risk of sampling errors.…”

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“…Available markers are CEA, CA 72-4, CA 19-9, and HER2 [69,70]. These are not specific for stomach cancers.…”

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“…First, several studies have failed to find a significant association between HER2 overexpression/amplification and decreased survival (particularly on multivariate analysis). A recent systematic review found that of 35 studies reporting the impact of HER2 overexpression on survival in gastric cancer only a small number found a significant association with poorer overall survival (13 vs. 22 studies) [8]. In two of the 22 studies, the opposite finding was found (i.e., significantly longer overall survival in patients with HER2 overexpression).…”