Abstract 5567: Impact of progesterone receptor (PR) isotype-specific immunohistochemistry (IHC) on the diagnosis of triple negative breast cancer (BC)

Abstract

Abstract Background: Given the poor therapeutic outcomes for triple negative BC, diagnostic accuracy is vital. In routine IHC, PR is measured using bispecific antibodies (Ab) that recognize epitopes common to PRA and PRB. PR A and B expression is imbalanced in BC. Relative expression of the PR isotypes appears to be prognostic in tumors evaluated with a bispecific Ab (Hopp 2004). Tumors can express PRA or PRB on different cells in the same tumor (Mote 2008), which differ from those expressing ERα (Zukiwski 2013). A true triple negative phenotype might escape detection with the use of one single Ab to detect both PR A and B epitopes, depending on its sensitivity/specificity. This study evaluated the use of two isotype-specific PR Abs to fully characterize PR status. Methods: 312 archived BC specimens with clinical data came from Oscar Lambret Cancer Center, Lille. HER2 status was previously determined. IHC was performed using anti-ERα, anti-PRA and PRB Abs. ERα and PR tumor positivity was defined as ≥ 1% stained tumor cells. Results: 276 cases had complete data. Table 1 shows ERα, PRA and PRB status. 38/276 cases (14%) were ERα and HER2 negative: 22 were PR A or B negative, 9 were PR A and B positive, 2 were positive only for PRA and 5 only for PRB. Discussion: Bispecific PR Abs rarely report PRA and PRB similarly (Mote 2001). PR Phosphorylation and activation may vary across tumors. Potentially only one PR isotype may drive BC tumor growth. Triple-negative BC status determination could be PR Ab-dependent. These cases are currently being tested with a standard bispecific PR Ab to understand which would be considered triple-negative with routine IHC. Conclusion: Further evaluation of IHC with specific PRA and PRB Abs is warranted to determine if certain patients, currently classified as having triple-negative BC, could respond to antiprogestins, which have shown activity in BC. Table 1% of276 casesPR (PRA or PRB)PRAPRBERαNegativePositiveTotalNegativePositiveTotalNegativePositiveTotalNegative148221742115722Positive77178146579106868Total217910031691002575100 Citation Format: Erard Gilles, Jacques Bosq, Laura Caplier, Alice Bexon, Alexander Zukiwski, Jacques Bonneterre. Impact of progesterone receptor (PR) isotype-specific immunohistochemistry (IHC) on the diagnosis of triple negative breast cancer (BC). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5567. doi:10.1158/1538-7445.AM2014-5567