What’s beyond BRCA Mutational Status in High Grade Serous Ovarian Cancer? The Impact of Hormone Receptor Expression in a Large BRCA-Profiled Ovarian Cancer Patient Series: A Retrospective Cohort Study

SIMPLE SUMMARY: Ovarian hormones are involved in ovarian cancer pathogenesis. However, few reports have investigated the hormone receptor pattern according to BRCA mutational status. The aim of this single-center, observational, retrospective study was to explore the relationship between hormone receptor status and BRCA1/2 mutation in a cohort of 207 high-grade serous ovarian carcinoma (HGSOC) patients. Interesting differences emerged between BRCA-mutated and BRCA wild-type women, in terms of pattern of receptor expression and its association to the outcome. On the whole, our findings, though needing further validation, extend our understanding of the complex interplay between BRCA1/2 protein and hormone signaling, suggesting new pathways to be exploited in order to develop future personalized therapy. ABSTRACT: Several studies have explored the prognostic role of hormone receptor status in high-grade serous ovarian cancer (HGSOC) patients. However, few reports have investigated their expression according to BRCA mutational status. The aim of this single-center, observational, retrospective study was to explore the hormone receptor pattern and its potential prognostic role in a cohort of 207 HGSOC women stratified for BRCA mutational status. To this end, ERα, ERβ1, ERβ2, ERβ5, PR, and AR expression were assessed by immunohistochemistry in 135 BRCA-wild type (BRCA-wt) and 72 BRCA1/2 mutation carriers (BRCA-mut). No significant difference emerged in hormone receptor expression between the two sub-samples, except for a significantly lower ERα expression observed in pre-menopausal BRCA1/2-mut as compared to BRCA-wt patients (p = 0.02). None of the examined hormone receptors has revealed a significant prognostic role in the whole sample, apart from the ratio ERα/ERβ5 nuclear, for which higher values disclosed a positive role on the outcome in BRCA-wt subgroup (HR 0.77; CI 0.61–0.96; p = 0.019). Conversely, it negatively affected overall survival in the presence of BRCA1/2-mut (HR 1.41; CI 1.06–1.87; p = 0.020). Finally, higher PR levels were associated with platinum sensitivity in the whole sample (p = 0.019). Our data, though needing further validation, suggest a potential role of oestrogen-mediated pathways in BRCA1/2-associated HGSOC tumorigenesis, thus revealing a possible therapeutic potential for targeting this interaction.