Diagnostic assays for human epidermal growth factor receptor 2 (HER2) expression have a high predictive value because patients with HER2-positive tumors could benefit from HER2-targeted therapy. The aim of the present study is to analyze the incidence of HER2 gene amplification in selected tumors with adverse features that scored 1+ by immunohistochemistry (IHC). For that purpose, 331 consecutive invasive breast cancers (IBCs) were tested by IHC for HER2 expression between January and December 2013, 102 of which (31%) scored 1+. Of these 102 women with IBC who underwent surgery, 75 entered the study (73.5%). A total of 48 out of 75 (64%) IBC samples (patients' median age, 60.75 years) were selected according to ≥1 unfavorable tumor characteristics, and tested by fluorescence in situ hybridization (FISH). Of these 48 IBC samples scoring 1+ by IHC, 22 (46%) exhibited high histological grade (G3), 23 (48%) had a high proliferative index (Ki-67, >30%), 27 (56%) showed vascular invasion and 32 out of 41 evaluable cases (78%) were node-positive. Regarding hormone receptor expression, 3 (6%) and 10 (21%) cases were negative for estrogen and progesterone receptors expression, respectively. FISH was performed on 48 IBC cases scoring 1+ by IHC, and 7 infiltrating ductal carcinomas (IDCs) (14.6%) demonstrated HER2 amplification with a high proliferative index. In 42 IDC samples, statistical analysis evidenced a significant association between histological grade and high proliferative index (P=0.0200). In addition, in 48 HER2 scoring 1+ IBCs, Fisher's exact test evidenced a significant association between the presence of gene amplification and high proliferative index (P=0.0033). Based on these biopathological parameters, particularly a high proliferative index, the present results indicate that it is possible to of identify tumors scoring 1+ by IHC with HER2 amplification by FISH, thus aiding the selection of patients who are suitable for HER2-targeted therapy according to an acceptable cost/benefit ratio.
Keywords: HER2; fluorescence in situ hybridization; immunohistochemistry score 1+; invasive breast cancer; targeted therapies.