Correlation Between HER2 Determined by Fluorescence In Situ Hybridization and Reverse Transcription-Polymerase Chain Reaction of the Oncotype DX Test

Dvorak, L; Dolan, Michelle; Fink, Jürgen; Varghese, Linda; Henriksen, Jonathan C.; Gulbahce, H. Evin

doi:10.1097/pai.0b013e3182632ff5

Cited by 21 publications

(19 citation statements)

References 10 publications

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“…Analysis of HER2 results comparing FISH and Oncotype DX revealed a very high concordance of 97.2%. High concordance rates (96–98%) have been published . A closer subset examination demonstrates a striking difference between the two assays.…”

Section: Discussionmentioning

confidence: 94%

ER and PR Immunohistochemistry and HER2 FISH versus Oncotype DX: Implications for Breast Cancer Treatment

et al. 2013

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Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor (HER2) concordance between immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), and Oncotype DX, a commercially available RT-PCR-based assay which recently began reporting biomarker results was assessed. ER concordance was 98.9% (262/265), Pearson correlation coefficient (r) = 0.42, and Spearman's rank correlation (ρ) = 0.25. Positive percent agreement for ER was 98.9% (262/265). One patient with discordant ER results was not offered hormone therapy based on the preferential use of Oncotype DX. PR was concordant in 91.3% (242/265), r = 0.80, ρ = 0.75, and Cohen's kappa (κ) = 0.63. Positive percent agreement for PR was 90.5% (218/241) and negative percent agreement was 100% (24/24). HER2 concordance was 99.2% (245/247), r = 0.35, ρ = 0.28, and κ = 0.12. Positive percent agreement for HER2 was 0% (0/2) and negative percent agreement was 100% (245/245). Of the three FISH HER2-amplified cases, two were negative and one was equivocal, and all FISH HER2-equivocal cases (n = 3) were negative by Oncotype DX. Patients that were FISH HER2-amplified, Oncotype DX HER2-negative did not receive trastuzumab. Although our results demonstrated high concordance between IHC and Oncotype DX for ER and PR, our data showed poor positive percent agreement for HER2. Compared to FISH, Oncotype DX does not identify HER2-positive breast carcinomas. The preferential use of Oncotype DX biomarker results over IHC and FISH is discouraged.

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Section: Discussionmentioning

confidence: 94%

ER and PR Immunohistochemistry and HER2 FISH versus Oncotype DX: Implications for Breast Cancer Treatment

et al. 2013

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“…Discrepancies may arise due to subjective interpretation of IHC and FISH results, arbitrary cut-off levels for positive results that may differ between the commercial kits, or due to a low percentage of invasive tumour in the tissue block when performing RT-PCR. [7,8] Our pathologysupported genetic testing strategy enables the evaluation of a combination of tests most likely to overcome the limitations of a single test procedure.…”

Section: Discussionmentioning

confidence: 99%

“…Multi-gene expression tests that are based on real-time polymerase chain reaction (RT-PCR) methodology, such as Oncotype Dx, have been criticised for lack of reproducibility in determination of HER2 overexpression, which forms an integral part of the recurrence score. [7,8] MammaPrint is the only test cleared by the US Food and Drug Administration (FDA), and this independent confirmation of analytical and clinical validation provides a high level of confidence in test performance.…”

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confidence: 99%

MammaPrint Pre-screen Algorithm (MPA) reduces chemotherapy in patients with early-stage breast cancer

et al. 2013

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Corresponding author: M J Kotze (maritha@sun.ac.za)Background. Clinical and pathological parameters may overestimate the need for chemotherapy in patients with early-stage breast cancer. More accurate determination of the risk of distant recurrence is now possible with use of genetic tests, such as the 70-gene MammaPrint profile. Objectives. A health technology assessment performed by a medical insurer in 2009 introduced a set of test eligibility criteria -the MammaPrint Pre-screen Algorithm (MPA) -applied in this study to determine the clinical usefulness of a pathology-supported genetic testing strategy, aimed at the reduction of healthcare costs.Methods. An implementation study was designed to take advantage of the fact that the 70-gene profile excludes analysis of hormone receptor and human epidermal growth factor receptor 2 (HER2) status, which form part of the MPA based partly on immunohistochemistry routinely performed in all breast cancer patients. The study population consisted of 104 South African women with early-stage breast carcinoma referred for MammaPrint. For the MammaPrint test, RNA was extracted from 60 fresh tumours (in 58 patients) and 46 formalin-fixed, paraffin-embedded (FFPE) tissue samples. Results. When applying the MPA for selection of patients eligible for MammaPrint testing, 95 of the 104 patients qualified. In this subgroup 62% (59/95) were classified as low risk. Similar distribution patterns for risk classification were obtained for RNA extracted from fresh tumours v. FFPE tissue samples. Conclusions. The 70-gene profile classifies approximately 40% of early-stage breast cancer patients as low-risk compared with 15% using conventional criteria. In comparison, more than 60% were shown to be low risk with use of the MPA validated in this study as an appropriate strategy to prevent chemotherapy overtreatment in patients with early-stage breast cancer.

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“…It has been suggested that HER2 status can be assessed with different approaches as a continuous variable and can be assessed on mRNA level [19]. HER2 gene amplification determined with FISH is strongly associated with elevated mRNA and protein levels and small studies have reported on the concordance of HER2 status by RT-PCR to that by IHC and FISH [20]–[22]; Two independent studies have reported on the concordance between HER2 Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) of the Oncotype Dx Test and the FDA-approved IHC/FISH assays and have yielded conflicting results [23], [24]. In the first study, a greater than 50% false-negative rate for Onco type DX RT-PCR for HER2 assessment was reported.…”

Section: Introductionmentioning

confidence: 99%

In Situ Quantitative Measurement of HER2mRNA Predicts Benefit from Trastuzumab-Containing Chemotherapy in a Cohort of Metastatic Breast Cancer Patients

et al. 2014

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BackgroundWe sought to determine the predictive value of in situ mRNA measurement compared to traditional methods on a cohort of trastuzumab-treated metastatic breast cancer patients.MethodsA tissue microarray composed of 149, classified as HER2-positive, metastatic breast cancers treated with various trastuzumab-containing chemotherapy regimens was constructed. HER2 intracellular domain(ICD), HER2 extracellular domain(ECD) and HER2 mRNA were assessed using AQUA. For HER2 protein evaluation, CB11 was used to measure ICD and SP3 to measure ECD of the HER2 receptor. In addition, HER2 mRNA status was assessed using RNAscope assay ERRB2 probe. Kaplan – Meier estimates were used for depicting time-to-event endpoints. Multivariate Cox regression models with backward elimination were used to assess the performance of markers as predictors of TTP and OS, after adjusting for important covariates.ResultsHER2 mRNA was correlated with ICD HER2, as measured by CB11 HER2, with ECD HER2 as measured by SP3 (Pearson’s Correlation Coefficient, r = 0.66 and 0.51 respectively) and with FISH HER2 (Spearman’s Correlation Coefficient, r = 0.75). All markers, HER2 mRNA, ICD HER2 and ECD HER2, along with FISH HER2, were found prognostic for OS (Log-rank p = 0.007, 0.005, 0.009 and 0.043 respectively), and except for FISH HER2, they were also prognostic for TTP Log-rank p = 0.036, 0.068 and 0.066 respectively) in this trastuzumab- treated cohort. Multivariate analysis showed that in the presence of pre-specified set of prognostic factors, among all biomarkers only ECD HER2, as measured by SP3, is strong prognostic factor for both TTP (HR = 0.54, 95% CI: 0.31–0.93, p = 0.027) and OS (HR = 0.39, 95%CI: 0.22–0.70, p = 0.002).ConclusionsThe expression of HER2 ICD and ECD as well as HER2 mRNA levels was significantly associated with TTP and OS in this trastuzumab-treated metastatic cohort. In situ assessment of HER2 mRNA has the potential to identify breast cancer patients who derive benefit from Trastuzumab treatment.

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Correlation Between HER2 Determined by Fluorescence In Situ Hybridization and Reverse Transcription-Polymerase Chain Reaction of the Oncotype DX Test

Cited by 21 publications

References 10 publications

ER and PR Immunohistochemistry and HER2 FISH versus Oncotype DX: Implications for Breast Cancer Treatment

ER and PR Immunohistochemistry and HER2 FISH versus Oncotype DX: Implications for Breast Cancer Treatment

MammaPrint Pre-screen Algorithm (MPA) reduces chemotherapy in patients with early-stage breast cancer

In Situ Quantitative Measurement of HER2mRNA Predicts Benefit from Trastuzumab-Containing Chemotherapy in a Cohort of Metastatic Breast Cancer Patients

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