Abstract 1281: Serum levels of the immunomodulatory protein, the progesterone induced blocking factor (PIBF) are not higher in women with progesterone (P) receptor (R) positive vs. negative breast cancer

Abstract

Abstract There is evidence that treatment with mifepristone a P receptor antagonist will provide a marked palliative effect for many human and murine spontaneous cancers. One proposed mechanism is that it may work by suppressing the expression of a unique immunomodulatory protein that amongst other things stabilizes perforin granules in natural killer (NK) cells and thus negates their cytolytic activity. In humans exposure to P causes a rapid rise in the serum of this protein called the PIBF. The origin for the circulating PIBF is from gamma/delta T cells and is initiated with P interacting with P receptors on gamma/delta T cells. PIBF exists as a 90 kDa nuclear protein occupying a centrosomal position in near proximity to BRCA-1 and is found in all rapidly growing cells including cancer cells. A 34-36 kDa splice variant is found in the cytoplasm of all cancer cells tested. Mifepristone has been found to provide marked palliation despite the absence of evidence of circulating PIBF in some cancers not known to be positive for P receptors. One possible mechanism is suppression of the formation of the 34-36 kDa intracytoplasmic form from the parent 90 kDa form. The objective of the present study was to determine if tumors known to be P receptor positive may demonstrate circulating PIBF. In a blinded manner, serum PIBF was measured in 21 serum samples of women with breast cancer obtained prior to surgery using a research ELISA assay for PIBF. The PIBF levels were then compared according to estrogen (E) and P receptor status. The mean level of PIBF (ng/mL) for those who were ER positive but P receptor negative in 7 cases was 31.0+49.7 with a range of 2.1 to 142.5. For 7 cases that were ER positive and P receptor positive the mean level +SD was 24.8+37.46 and the range 2.4 to 108.32. For ER negative and P receptor positive for 7 cases, the mean PIBF was 24.6+28.3 and the range 6.0 to 86.9. There were no significant differences by ANOVA. It is not clear as yet if P receptor antagonist therapy will provide better palliative effect for P receptor positive vs. P receptor negative tumors, but if so, the mechanism (if it is immunologic) does not seem to be related to suppressing increased levels of circulating PIBF. Thus, testing serum with this new ELISA assay does not seem to be a helpful method to determine which patients may benefit from P receptor antagonist therapy. Some recent data suggest that the P receptor antagonist may suppress intracellular PIBF but not circulative PIBF. Thus, these data do not exclude the possibility that PIBF may play a vital role in escape of cancer cells from immune surveillance but it is the intracytoplasmic form that provides immune protection. Citation Format: Jerome H. Check, Anne Rosenberg, Ann DiAntonio, Hallgeir Rui, Rachael Cohen, Gabrielle DiAntonio. Serum levels of the immunomodulatory protein, the progesterone induced blocking factor (PIBF) are not higher in women with progesterone (P) receptor (R) positive vs. negative breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1281. doi:10.1158/1538-7445.AM2015-1281