Marked Palliative Benefits Seen With Treatment of Very Advanced Breast Cancer With the Progesterone Receptor Modulator Mifepristone

Background/Aim: Treatment of cancers known to be positive for the nuclear progesterone receptor (nPR), e.g., breast, ovarian, and endometrial cancers with PR modulators/antagonists, e.g., mifepristone, have not shown impressive improvement in palliative or longevity benefits. In contrast, several case reports showed considerable palliation and/or extension of life using mifepristone treatment for various advanced cancers devoid of the nPR. The aim of this study was to determine whether mifepristone therapy could provide improved quality of life in a patient with breast cancer considered terminal based on extensive brain and lung metastases in which the estrogen receptor (ER) was present in 99% of the cells but only 1% positive for the nPR.

Case Report: A 64-year-old woman with stage IV breast cancer with very symptomatic brain and lung metastases who was considered terminal was first treated with letrozole. She failed to show any clinical improvement. Attempts to also treat her with abemaciclib and subsequently ribociclib were stopped after a very short course related to side effects. Mifepristone 200 mg daily tablets resulted in marked improvement in her fatigue, dyspnea on exertion, cognition, and her issues with balance. This was associated with a 75% reduction in the size of the lung lesions and no new metastatic lesions by position emission tomography two months after starting mifepristone. She lived eight months and still maintained good quality of life, but she died of a cerebral vascular accident.

Conclusion: Mifepristone provided marked palliative benefit in this patient with nPR-negative, metastatic breast cancer, suggesting potential therapeutic value in similar cases. Confirmation of efficacy will require larger studies focused on tumors with absent or minimal nuclear progesterone receptor expression.