Abstract P5-10-17: Evaluation of PgR status by immunohistochemistry may be inferior to PgR results by Oncotype DX for assessing the recurrence risk in ER+/HER2- breast cancer with low or intermediate tumor proliferation

Abstract

Abstract Background: Loss of progesterone receptor expression is known to be a predictor of Luminal-B subtype, and is of independent prognostic significance in luminal type breast cancer. However, the threshold of PgR status in IHC has been subject to debate, and the PgR status as reported by IHC not infrequently is at variance with the PgR result as reported by the Oncotype DX (ODX) assay. Methods: We retrospectively reviewed tumor IHC and ODX data from resection specimens with ER+/HER2- breast cancer, and low to intermediate Ki-67 proliferation rates (Ki-67 < 30%). A total of 74 specimens were re-analyzed, all from resection specimens that had been selected for ODX assay for the purpose of planning of adjuvant chemotherapy, from two institutions (Univ. Heidelberg, Germany, and Univ. Zurich, Switzerland). PgR expression of < 10% using IHC (clone PgR636, Ventana and Dako systems) or PgR values of < 5,5 in ODX assay were considered negative. Results: All cases were positive for ER by IHC and ODX, and 20% were negative for PgR by ODX assay. This compared to only 8% of negativity by IHC, but all except one case negative for PgR by IHC were also correctly identified as PgR negative by ODX. Median ODX recurrence score (RS) was 35 for PgR negativity by ODX assay, as compared to 30 for negative PgR status by IHC. For positive PgR status, median RS was calculated as 15 vs. 17 by ODX vs. IHC. Risk categories by ODX were high (RS >= 31) in 9 cases with negative PgR status by ODX, but only 3 of these high risk cases were negative for PgR by IHC. Median Ki-67 values were 22.5 for PgR negative cases by ODX as compared to 15 for PgR negative cases by IHC. Similar results were obtained when a higher PgR threshold of 20% was applied to IHC results. Conclusions: In luminal type breast cancers, the evaluation of PgR status by IHC may underestimate the proportion of PgR negative cases and did not identify most cases of tumors with a high risk of recurrence. This may be caused by an overly high sensitivity of PgR status in routine automated immunohistochemistry. Citation Format: Peter Sinn, Mark Kriegsmann, Ute Felten, Jürgen Wacker, Andreas Schneeweiss, Zsuzsanna Varga. Evaluation of PgR status by immunohistochemistry may be inferior to PgR results by Oncotype DX for assessing the recurrence risk in ER+/HER2- breast cancer with low or intermediate tumor proliferation [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 P5-10-17.