Predictive role of HER-2/neu overexpression and clinical features at initial presentation in patients with extensive stage small cell lung carcinoma

Although recent advances in therapy have improved the quality of life in patients with extensive stage small cell lung cancer (ESSCLC), prolonged survival is still uncommon. To determine the role of HER-2/neu overexpression and other clinical predictors (symptoms at presentation) of adverse outcome in ESSCLC, we performed a retrospective study on subjects with a biopsy-proven diagnosis of ESSCLC. HER-2/neu overexpression was evaluated using immunohistochemistry (IHC) performed on paraffin-embedded specimens. An IHC score of ≥2+ was considered positive for overexpression. Between 1991 and 2000, 223 patients with ESSCLC were identified, of whom 193 patients (84 females, 109 males) with a mean age of 68.5 years (range: 42-90 years) had adequate tissue specimens for HER-2/neu testing. The symptoms at initial presentation and proportionate number of patients were: weight loss 61 (31.6%), cough 53 (27.5%), dyspnea 33 (17.1%), mass on chest radiograph 18 (9.3%), chest pain 15 (7.7%), asymptomatic 14 (7.2%) and others (weakness, lymphadenopathy, hoarseness and paraneoplastic syndromes) 29 (15.0%). Of the 193 specimens, 57 (29.5%) revealed HER-2/neu overexpression. The median survival for patients with ESSCLC who were HER-2/neu positive was 8 months (range: 1-25.5 months) while that in the HER-2/neu negative group was 16 months (range: 2-34 months). Interestingly, after adjusting for age, performance status and type of therapy, subset analysis revealed that the survival was significantly lower in HER-2/neu positive individuals (P<0.001; Mann-Whitney U-test). In our study, weight loss and cough were the two most common (59%) presenting complaints in patients with ESSCLC. Also, since HER-2/neu positivity was a marker for poor prognosis in ESSCLC, testing for overexpression may play a role in identifying patients at risk for shortened survival. Further studies would delineate whether HER-2/neu overexpression renders SCLC chemoresistant and thus, adversely affects outcome. There exists a need for randomized controlled trials to assess the role of Herceptin (alone or in combination with standard chemotherapy) in patients with ESSCLC.