YO6 - Challenging case study of a transgender prostate cancer patient

Case summary

Title: Challenging case study of a transgender prostate cancer patient

Background:

Prostate cancer (PC) is a leading cause of cancer death [1]. There is little known regarding PC in the male-to-female transgender population [2-9].

Methods:

A 69-year-old transgender woman diagnosed with PC in March 2010, with no cancer family, underwent feminisation in her early fifties with oral oestrogen. She underwent orchidectomy in July 2010 after bicalutamide. At presentation, PSA was 5.71. Pathology demonstrated a pT3a N0 M0 Gleason 4+5 PC. She received local brachytherapy and radical radiotherapy but developed metastatic disease in June 2015, receiving enzalutamide, stopped due to grade two fatigue and memory disturbance and then abiraterone for one year, with best response of stable disease. She then received docetaxel, maintaining stable disease for one year and, upon progressive disease, she received cabazitaxel in July 2018 respectively. In June 2019, she was referred for consideration of clinical trials at which point her estrogen was stopped, however, did not experience withdrawal response for which a biopsy was performed in 2020 for tumour molecular characterisation.

Results:

Immunohistochemical (IHC) evaluation of diagnostic hormone-sensitive PC demonstrated positive androgen receptor (AR) staining and oestrogen receptor alpha (ERa) staining. ERa expression was not related to tumour grade, with staining seen in both low grade and high grade areas. AR expression was markedly higher in castration-resistant PC (CRPC) biopsies but ERa levels were greatly reduced, also identifying highly expressed AR splice variant 7 (AR-V7), ATM loss, and a high CD3 count. Targeted next generation sequencing of the CRPC biopsy revealed NBN and WT1 deep deletions, AR and ATRX amplification and BRAF pathogenic mutations (p.K601E, p.R509Q); transcriptome analysis identified higher than median (95 mCRPC RNAseq cohort) AR and ARV7, but not ERa, mRNA expression with very high ARV7 but very low ER pathway activity at signature level [10].

Conclusions:

This transgender patients’ data suggest that exogenous estrogen may fuel PC development and growth through AR signalling; estrogen dose reductions in these subjects need to be considered to decrease PC risk.

Clinical trial identification

Editorial acknowledgement