HIJACKING HORMONE SIGNALING IN BREAST CANCER: GLUCOCORTICOID RECEPTOR AFFINITY FOR MIFEPRISTONE (RU486) MAY UNLOCK PATIENT SURVIVAL macy.jepsen.25@tmsu.edu.vc

425-06

HIJACKING HORMONE SIGNALING IN BREAST CANCER: GLUCOCORTICOID RECEPTOR AFFINITY FOR MIFEPRISTONE (RU486) MAY UNLOCK PATIENT SURVIVAL

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Saint Vincent

Oral or Poster

Glucocorticoid receptor (GR) signaling plays a dual role in breast cancer, influencing both tumor suppression and progression. While glucocorticoids (GCs) are commonly used to manage chemotherapy side effects, they can also promote chemoresistance, immune evasion, and tumor growth. Mifepristone (RU486), a selective GR antagonist and anti-progesterone agent, has emerged as a potential therapy to counter these adverse effects by restoring chemotherapy sensitivity and modulating immune responses. This systematic review explores mifepristone’s potential to target GR-mediated pathways, aiming to improve outcomes in breast cancer patients.

A systematic review was conducted in line with PRISMA guidelines. Searches of PubMed, Cochrane Library, and EBSCO identified 450 peer-reviewed studies from the past decade. Thirty met inclusion criteria, focusing on human breast cancer cases involving GCs or RU486. Key data on treatment response, chemoresistance, immune modulation, survival, and recurrence were extracted. Study quality was assessed using the Cochrane Risk of Bias Tool.

GC exposure correlated with increased recurrence, metastasis, chemoresistance, and reduced immune surveillance. RU486 significantly inhibited GR activity, reducing proliferation markers by 50%, reversing GC-induced chemoresistance, enhancing immune infiltration, and promoting apoptosis. It also showed promise in preventing metastasis via extracellular matrix remodeling and in reducing cancer incidence in BRCA1/2 carriers. RU486 disrupted cortisol-driven inflammatory and metabolic pathways linked to recurrence, and was particularly effective in tumors with high progesterone receptor isoform A.

RU486 shows promise as a therapeutic adjunct by delivering both anti-cancer effects and reversing glucocorticoid-induced adverse outcomes, particularly in hormone-dependent and triple-negative breast cancers. Further clinical research is warranted.