Is Uveal Melanoma a Hormonally Sensitive Cancer? A Review of the Impact of Sex Hormones and Pregnancy on Uveal Melanoma.

Background: Despite a higher incidence and worse prognosis of uveal melanoma (UM) in men, there have been many case reports of pregnant patients with aggressive UM. This has led researchers to explore the influence of sex hormones and pregnancy on the development and progression of UM and hormones as potential therapeutic targets.

Summary: A systematic literature review was conducted. More work is needed to elucidate the basis of sex differences in UM incidence and survival. The evaluation of germline mutation would be beneficial in patients with UM presenting at a young age. Importantly, multiple studies reported no significant difference between the 5-year survival and 5-year metastasis-free survival rates between nonpregnant women with UM and pregnant women with UM. Multiple case-control studies disagree on how parity affects risk of UM. However, most studies agree that oral contraceptives and hormone replacement therapy have no effect on the incidence of UM. Current treatment strategies for pregnant patients with UM are discussed. Looking forward, this review reports recent research on targeted receptor-based chemotherapy, which is based on evidence of estrogen receptor (ER), estrogen-related receptor alpha (ERRα), and luteinizing hormone-releasing hormone (LHRH) receptor expression in UM.

Key Messages: Based on review of the literature, UM is not a contraindication to oral contraceptives, hormone replacement therapy, or pregnancy. Globe-sparing radiation can be used as a treatment option for pregnant patients. Due to the presence of ER on a subset of unselected UM, its potential for adjunctive targeted therapy with agents like tamoxifen should be explored. Lessons from cutaneous melanoma regarding tissue ratios of estrogen receptors (ERα:ERβ) should be applied to assess their therapeutic predictive value. In addition, ERRα-targeted therapeutics and LHRH analogs are worthy of further exploration in UM.