Population-based study of hormone receptor status comparing OncotypeDX with standard immunohistochemistry
KeywordsEstrogen Receptor Progesterone Receptor Hormone Receptor Recurrence Score Progesterone Receptor Status
Accurate measurement of hormone receptor (HR) status is important as hormonal therapy reduces risk of recurrence by >50% in breast cancer patients with hormone-sensitive tumors. We compared estrogen receptor (ER) and progesterone receptor (PR) results obtained with Oncotype DX, a validated 21-gene recurrence score assay that utilizes quantitative RT-PCR, with results from established immunohistochemistry (IHC).
Breast cancer specimens from the Kaiser Oncotype DX study were evaluated by IHC for ER (SP1) and PR (636) using ≥ 1% staining for positivity. ER and PR status was also determined using Oncotype DX (RT-PCR) with pre-defined positivity cutoff values of 6.5 units and 5.5 units, respectively (each unit = twofold change in expression). HR positivity was defined as ER+ and/or PR+.
The overall concordance in 607 evaluable patients (95% CI) between IHC and Oncotype DX was 96% for ER, 90% for PR, and 95% for HR (all P < 0.0001). The kappa (95% CI) between IHC and Oncotype DX was 83% for ER, 76% for PR, and 81% for HR (all P < 0.0001). For discordant pairs that were within cutoff limits, there were 20 that were IHC ER- but ER+ by Oncotype DX, 17 (85%) of which were within cutoff limits; another 38 were IHC PR- but PR+ by Oncotype DX, 23 (61%) of which were within cutoff limits; seven pairs were IHC ER+ but ER- by Oncotype DX, six (86%) of which were within cutoff limits; and 22 pairs were IHC PR+ but Oncotype DX PR-, 19 (86%) of which were within cutoff limits.
There was a high degree of concordance between Oncotype DX and standard IHC methods for ER, PR and HR status, indicating Oncotype DX may be a valid alternative to IHC. The notable incidence of IHC HR-negative patients who were Oncotype DX HR-positive, which could affect treatment decisions, deserves further study.
FLB is an employee and shareholder of Genomic Health, Inc.
Supported by funding from Genomic Health Inc.