Treatment with trastuzumab is indicated in cases where HER2 expression has a score of 3+. However, IHC has been shown to have numerous limitations, both technical and interpretative, which have been found to impact on the reproducibility and accuracy of results, especially when compared with ISH methodologies. It is also true, however, that some reports have stated that IHC provides excellent correlation between gene copy number and protein expression.Fluorescent in situ hybridization (FISH) is viewed as being the "gold standard" technique in identifying patients who would benefit from trastuzumab, but it is expensive and requires fluorescence microscopy and an image capture system. The main expense involved with CISH is in the purchase of FDA-approved kits, and as it is not a fluorescent technique it does not require specialist microscopy and slides may be kept permanently. Comparative studies of CISH and FISH have shown that these two techniques show excellent correlation. The lack of a separate chromosome 17 probe on the same section is an issue with regards to acceptance of CISH. As of June 2011 Roche has obtained FDA approval for the INFORM HER2 Dual ISH DNA Probe cocktail  developed by Ventana Medical Systems. The DDISH (Dual-chromagen/Dual-hapten In-situ hybridization) cocktail uses both HER2 and Chromosome 17 hybridization probes for chromagenic visualization on the same tissue section.
In these trials, trastuzumab also increased the risk of heart problems, including heart failure and left ventricular ejection fraction decline.In early-stage HER2-positive breast cancer, trastuzumab-containing regimens improved overall survival (Hazard ratio (HR) = 0.66) and disease-free survival (HR = 0.60). Increased risk of heart failure (RR = 5.11) and decline in left ventricular ejection fraction (relative risk RR = 1.83) were seen in these trials as well. Two trials involving shorter term treatment with trastuzumab did not differ in efficacy from longer trials, but produced less cardiac toxicity.The original studies of trastuzumab showed that it improved overall survival in late-stage (metastatic) HER2-positive breast cancer from 20.3 to 25.1 months. In early-stage HER2-positive breast cancer, it reduces the risk of cancer returning after surgery. The absolute reduction in the risk of cancer returning within three years was 9.5%, and the absolute reduction in the risk of death within 3 years was reduced by 3%. However, it increases serious heart problems by an absolute risk of 2.1%, though the problems may resolve if treatment is stopped.Trastuzumab has had a "major impact in the treatment of HER2-positive metastatic breast cancer." The combination of trastuzumab with chemotherapy has been shown to increase both survival and response rate, in comparison to trastuzumab alone.It is possible to determine the "erbB2 status" of a tumor, which can be used to predict efficacy of treatment with trastuzumab.