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

Abstract

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.

Distribution patterns of 21-gene recurrence score in 980 Chinese estrogen receptor-positive, HER2-negative early breast cancer patients

“…There has been growing interest in molecular biomarker testing by RT-PCR with conflicting results [15–20]. In our study, ER displayed a very high concordance of 98.8% between IHC and RT-PCR, in accordance with the literature (93% to 100%).…”

Macrodissection prior to closed system RT-qPCR is not necessary for estrogen receptor and HER2 concordance with IHC/FISH in breast cancer

“…10 Over the years, the measurement of RNA for breast cancer markers has emerged using several commercially available platforms 22–24 , most significantly for multi-parameter prognostic testing. However simple qRT-PCR has failed to gain acceptance for HER2 assessment.…”

Relevance of progesterone receptor immunohistochemical staining to Oncotype DX recurrence score

“…Oncotype DX RS is predictive of patient's benefit from adjuvant chemotherapy in both the low and high RS categories based on the rate of distant recurrence at 10 years. However, the data and suggested treatment strategy for intermediate RS patients are less clear and will likely remain so until the results from the Trial Assigning IndividuaLized Options for Treatment (TAILORx) trial become available [24]. When weighing the treatment options for the patients in the intermediate RS category, the PR status may be an important factor to consider in clinical decision making.…”

“…For ER, the concordance between central IHC and RT-PCR was 93%, whereas for PR the concordance was 88%. Park et al [24] reported 98.9% concordance for ER and 91.3% concordance for PR when IHC and RT-PCR were compared in 265 breast cancer patients. In another study of 464 breast cancer cases, comparison of hormone receptor status reported by IHC and RT-PCR showed a good concordance of 98.9% for ER and 94.2% for PR status [28].…”