FISH in Triple-negative Breast Cancer: A Possible Strategy for the Future?

Elisa Rigon; Chiara Saggia; Valentina Rossi; Silvia Genestroni; Erica Gaudino; Paola Campisi; Claudia Veggiani; Renzo Luciano Boldorini; Oscar Alabiso


Future Oncol. 2015;11(7):1023-1026. 

In This Article

Discordance Between IHC & FISH

The identification of the discordance between IHC 1+ or 0 and positive FISH is a major point to be addressed in the treatment of TNBCs, as it would help the correct selection of HER2-positive patients. Tumors classified as 0/1+ and 3+ by IHC and FISH usually show concordant results, while a higher grade of discordance is often found in cases scored 2+ by IHC that require further investigation. In a study conducted by Dybdal et al. the overall concordance rate measured between IHC and FISH assays was 82%: the HER2 amplification in the 0, 1+, 2+ and 3+ groups was observed in 3.2, 6.7, 23.9 and 89.3% of the samples, respectively.[11]

A number of other studies investigated the discordance between IHC and FISH in breast cancer.

Iorfida et al. conducted a prospective observational study to assess the incidence of HER2 gene amplification in 492 invasive breast carcinomas classified as IHC 1+. The FISH test was carried out in 84 cases (17%), selected according to characteristics such as: high grade, high Ki67, extensive vascular invasion, node positivity and uncertain or absent endocrine responsiveness. The results of the FISH test were positive in 13% of the patients with an IHC 1+ breast cancer, about twofold the result observed in previous studies (˜6.7%).[11] Based on these observations the authors suggest that, in addition to the current algorithm that recommends FISH in IHC 2+ cases, the FISH test should be performed in IHC 1+ breast cancers with adverse prognostic features.[12]

A recent meta-analysis on 6629 patients showed that the overall discordance rate between IHC 0/1+ and FISH test for the detection of HER2 overexpression was 4%. Therefore, an IHC result of 0/1+ cannot be completely considered as negative and the execution of a valid and complementary test, such as the FISH assay, is highly recommended to better define HER2 expression.[13]

A study on 789 breast cancer patients showed that both patients with discordant receptor status and those with concordant TNBC had similarly unfavorable survival, probably due to an inappropriate use of targeted therapies. The authors emphasized the importance of correctly determining hormone and HER2 receptor status as a fundamental step to achieve the therapeutic effect of targeted therapies and avoid suboptimal treatment. In addition they suggest that a correlation might exist between the discordance in receptor expression and the lack of reliability of measurement methods.[14]

This hypothesis is further supported by a French study that compared different techniques aimed at measuring HER2 expression, concluding that the discordances reported between techniques might be due to HER2 intratumor heterogeneity, such as one tumor containing two distinct clones or tumors consisting of HER2 amplified and nonamplified subclones. The authors also suggested that the combination of IHC with FISH or Q-RT-PCR in IHC equivocal cases or even in all tumors may be a reliable and moderate-cost strategy for HER2 status assessment.[15]