Problems and Solutions in the Evaluation of Hormone Receptors in Breast Cancer

Oncology describes an interesting study comparing two methods of assessing estrogen-receptor (ER) and progesterone-receptor (PR) ex-pression in invasive breast cancer (IBC). Onemethodmeasured pro-tein by immunohistochemistry (IHC) and the other measured RNA using quantitative reverse-transcription polymerase chain reaction (RT-PCR). All assays utilized formalin-fixed, paraffin-embedded tis-sue samples fromacase-control studycohortderived fromtheEastern Cooperative Oncology Group clinical trial E2197, which randomly assigned patients with high-risk IBC to adjuvant doxorubicin/cyclo-phosphamide versus doxorubicin/docetaxel, with the addition of ta-moxifen in receptor-positive cases.2 The cases (n 179) represented all patients who relapsed (5 years follow-up) matched to an excess of controls (n 597)whodid not relapse, with available paraffinblocks. The IHC assays were performed twice in different laboratories. One was in the laboratories of institutions using local (and almost certainly diverse) staining protocols and definitions of positivity, most likely evaluating single 3- to 5-m histologic sections from intact paraffin blocks of tumor. The other was in an expert central laboratory using a standardized staining protocol on single 3- to 5-m sections from tissue microarrays (TMAs) containing two 1.0-mm cores from each tumor, with positive defined as an Allred Score of more than 2 (cor-responding to 1%to10%weakly positive cells).3,4 TheRT-PCRassays were conducted with RNA extracted from multiple (three to six) 10-msections of intact paraffinblocks atGenomicHealth Inc (GHI; RedwoodCity,CA)using theOncotypeDXassay,5which evaluates 21 genes todetermineaRecurrenceScore (RS).Thegenes includeERand PR, with definitions of positive (6.5 and 5.5 units, respectively) deter-mined in previous studies.5 Overall, there was a fairly high concor-dance of positive and negative results across all assays, ranging from