Abstract P4-11-31: Inverse relationship between ER+/PR- breast cancer and OncotypeDx scores and concordance between IHC and RT-PCR

Abstract

Abstract Background Estrogen receptor-positive/progesterone-receptor negative breast cancer (ER+/PR- BC) is recognized as a distinct clinical entity that is associated with potentially more aggressive tumor biology and early resistance to endocrine therapy when compared to ER+/PR+ BC. The OncotypeDx assay provides risk stratification and prognostic information for hormone receptor (HR)-positive invasive BC; however, the association between the PR status determined by immunohistochemistry (IHC) and by OncotypeDx genomic analysis and the impact on the recurrence score (RS) is less clear. Methods We designed an analysis to determine whether OncotypeDx scores differ between ER+/PR+ and ER+/PR- tumors. Three hundred and fifty patients (pts) with HR positive, node-negative invasive BC who underwent OncotypeDx testing at our institution between Dec 2006-Oct 2013 were included in our study. We examined whether there was discordance in the HR status on IHC staining reported by our pathologists and the RT-PCR analysis reported as part of the OncotypeDx assay. The data were analyzed by ANOVA-F test and t-test. Chi-square test was used to analyze the discrepancies between the two methods of tumor genomic profile assessment. Results The mean age at diagnosis was 58 yrs (SD ±10.1 yrs). Three hundred and one pts had ER+/PR+ and 47 pts had ER+/PR- tumors by IHC. Pt characteristics are shown in Table 1. PR- tumors had significantly higher OncotypeDx scores than PR+ tumors (24.7 ±8.53 vs 17.3 ±7.38; Mean ±SD; p <0.001), predicting a greater 10-yr risk of distant recurrence. Two hundred and eighty four pts had HR status reported by OncotypeDx assay. Comparison of IHC and OncotypeDx assay revealed that 20 pts (8.1%) who were ER+/PR+ by IHC had ER+/PR- tumors by RT-PCR. Of the ER+/PR- cases by IHC, 12 (31.6%) were ER+/PR+ and 2 (5.3%) pts were ER-/PR- by RT-PCR (p <0.001, Table 2). Independent evaluation for ER and PR expression showed a concordance of 99.3% for ER and 88.7% for PR between the two methods. Conclusion Our study shows that ER+/PR- BC tumors are associated with a significantly higher OncotypeDx scores; this interprets into a higher risk of recurrence. Our data also show that there was a high concordance of 99.3% for ER between IHC and RT-PCR analyses whereas the concordance for PR was much lower at 88.7%. Patient characteristicsVariablesER+/PR+ N=303 (%)ER+/PR- N=47 (%)AgeMean5859M statusM207 (68.3)39 (83)PM96 (31.7)8 (17)OncotypeDx score♦N30147Mean ± SD17.3 ± 7.3824.7 ± 8.53HistologyIDC248 (82.4)44 (93.6)ILC50 (16.6)3 (6.4)StageT1a2 (0.7)2 (4.2)T1b49 (16.2)9 (19.1)T1c174 (57.5)25 (53.3)T274 (24.5)11 (23.4)T32 (0.7)0SurgeryLumpectomy198 (65.6)30 (63.8)Mastectomy102 (33.8)17 (36.1)ChemotherapyYes93 (30.4)32 (68.1)No210 (69.6)15 (31.9)Endocrine txAI167 (55.4)30 (65.2)Tam89 (29.2)9 (19.5)Sequential AI & Tam36 (10.9)4 (8.8)N= number, SD= standard deviation, M= menopausal, PM= premenopausal, IDC= invasive ductal carcinoma, ILC= invasive lobular carcinoma, AI= aromatase inhibitor, Tam= tamoxifen, ♦= statistically significant Comparison between IHC and RT-PCRIHCRT-PCRER+/PR+ N(%)ER+/PR- N(%)P valueER+/PR+226 (91.9)12 (31.6)< 0.001ER+/PR-20 (8.1)24 (63.2)ER-/PR-02 (5.3) Citation Format: Lubna N Chaudhary, Zeeshan Jawa, Aniko Szabo, Alexis Visotcky, Christopher R Chitambar. Inverse relationship between ER+/PR- breast cancer and OncotypeDx scores and concordance between IHC and RT-PCR [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-11-31.