High her2/centromeric probeforchromosome17fluorescence insitu hybridization ratio predicts pathologic complete response and survival outcomein patients receiving neoadjuvant systemic therapy with trastuzumab for her2-overexpressing locally advanced breast cancer

Background. The present study was performed to determine whether the human epidermal growth factor receptor-related 2 (HER2)/centromeric probe for chromosome 17 fluorescence in situ hybridization (FISH) ratio is a predictor of a pathologic complete response (pCR), recurrence-free survival (RFS), and/or overall survival (OS) in patients receiving neoadjuvant systemic treatment (NST) with trastuzumab (NST-T) forHER2+ locally advanced breast cancer (LABC). PatientsandMethods.Thepresentretrospectivestudy included 555 patients with HER2+ LABC who had undergone NST and definitive surgery (1999–2012); 373 had concurrently received trastuzumab. HER2-positivity was considered present with an immunohistochemical score of 3+ and/or HER2 FISH ratio of ≥2.0.We used logistic regression analysis and Cox proportional hazard modeling to determine whether a high HER2 FISH ratio, either as a continuous variable or with a cutoff of ≥7.0, would predict forpCR(no invasive disease in thebreast andno tumor in the ipsilateral axillary lymph nodes), RFS, and/or OS. Results. The pCR group’smedian HER2 FISH ratio was significantly higher than that of the non-pCR group (6.4 vs. 5.2; p=.003). The logistic regression model demonstrated that the independent predictors of pCR included a high HER2 FISH ratio as a continuous variable (p =.04). The multicovariate Cox proportional hazard model showed that a highHER2 FISH ratio (with a cutoff of ≥7.0 or as a continuous variable) was a significant prognostic indicator of longerRFStime(p=.047and p=.04, respectively). Similarly,ahigh HER2 FISH ratio of ≥7.0 was associated with longer OS (p=.06). Conclusion. A high HER2 FISH ratio is a predictor of pCR in patients with HER21LABC who receive NST-T.