HER2 as a prognostic factor

E. Strong (ed.). Gastric cancer. Principles and practice. Springer (2015)

Unlike in breast cancer patients, the role of HER2 positivity as a prognostic factor in gastric cancer remains controversial. A number of retrospective studies have demonstrated that HER2 positivity (by IHC and/or FISH) is a prognostic factor associated with increased risk of invasion, metastasis, and worse survival. In surgical series, HER2 status has been associated as the second poorest prognostic variable after nodal status [11, 12].

However, other studies found no association between HER2 and prognosis in both resectable and advanced stage disease. One large surgical series reviewing 829 resected stage II and III gastric cancer showed that HER2 status was not associated with the overall or recurrence free survival in both univariate and multivariate analyses [13]. Similar findings have been shown in the metastatic setting [14, 15]. The impact of HER2 status was correlated with patient outcome in one large study of 338 advanced gastric cancer patients from six prospective first-line therapeutic trials of chemotherapy without trastuzumab performed in the USA and Europe. Interestingly, the median overall survival was longer in HER2positive patients (13.9 versus 11.4 months, p = 0.047) in the univariate analysis. However, this prognostic value disappeared in multivariate analysis (p = 0.3). In addition, the HER2-positive disease was not prognostic in subgroup analysis based on tumor histology [16].

In the ToGA study, the median survival of HER2-positive patients on the control arm (nontrastuzumab) was similar to the historic comparison with phase III studies of 5-Fluoruracil and cisplatin in metastatic gastric cancer [17, 18]. In a recent phase III trial, adding cetuximab to capecitabine and a cisplatin-based chemotherapy, the subset of patients testing HER2-positive had superior outcomes compared to HER2 negative patients, irrespective of the therapy [19]. Unlike breast cancer where HER2-positive disease carries an adverse prognostic value, the prognostic role of HER2 overexpression in advanced or resectable gastric cancers remains unclear at this time.

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