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

• Published in: Cancers Vol. 14; no. 19; p. 4588
• Main Authors: Perrone, Emanuele, Tudisco, Riccardo, Pafundi, Pia Clara, Guido, Davide, Ciucci, Alessandra, Martinelli, Enrica, Zannoni, Gian Franco, Piermattei, Alessia, Spadola, Saveria, Ferrante, Giulia, Marchetti, Claudia, Scambia, Giovanni, Fagotti, Anna, Gallo, Daniela
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 22.09.2022; MDPI
• Subjects: androgen receptor; Androgens; BRCA1 protein; Breast cancer; Cohort analysis; estrogen receptors; Estrogens; Gene expression; Genetic aspects; Health aspects; HGSOC; Hormone receptors; Immunohistochemistry; Ligands; Menopause; Mutation; Mutation (Biology); Ovarian cancer; Ovarian carcinoma; Patients; Premenopause; progesterone receptor; Steroids; Transcription factors; Tumorigenesis; Womens health; Italy
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers14194588

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.