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2022-RA-685-ESGO What is beyond brca mutational status in high grade serous ovarian cancer? The role of hormone receptors expression
  1. Emanuele Perrone1,
  2. Riccardo Tudisco2,
  3. Pia Clara Pafundi3,
  4. Davide Guido4,
  5. Alessandra Ciucci5,
  6. Enrica Martinelli5,
  7. Gian Franco Zannoni6,
  8. Alessia Piermattei6,
  9. Claudia Marchetti1,
  10. Camilla Nero1,
  11. Daniela Gallo5,
  12. Giovanni Scambia1 and
  13. Anna Fagotti1
  1. 1Gynecologic Oncology Unit, Dipartimento per le Scienze della Salute della Donna del Bambino e di Sa, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
  2. 2Dipartimento per le Scienze della Salute della Donna del Bambino e di Sa, Universita’ Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS. Rome, Italy., Rome, Italy
  3. 3Facility of Epidemiology and Biostatistics, Gemelli Generator, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
  4. 4Bioinformatics Facility Core Research, Gemelli Science and Technology Park (GSTeP), Fondazione Policlinico Universitario A. Gemelli, IRCCS, Roma, Italy., Rome, Italy
  5. 5Unit of Translational Medicine for Woman and Child Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy, Rome, Italy
  6. 6Gynecopathology and Breast Pathology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy


Introduction/Background Several studies have explored the prognostic role of hormone receptor status in high grade serous ovarian cancer (HGSOC). However, few reports have investigated their expression according to BRCA mutational status. Notably, there is evidences of a strong interaction between BRCA1/2 proteins and steroid hormones system, including higher titres of estradiol and progesterone in BRCA1/BRCA2 mutation carriers. Thus, we sought to explore the hormone receptor pattern and its potential prognostic impact in a well-characterized cohort of HGSOC patients stratified for BRCA status.

Methodology We assessed ERα, ERβ1, ERβ2, ERβ5, PR (progesterone receptor) and AR (androgen receptor) expression by immunohistochemistry in a single-centre observational retrospective cohort study of 207 HGSOC women, profiled for BRCA-1/2 mutation status with available clinical and molecular features.

Results 135 BRCA-wild type (BRCA-wt) and 72 BRCA1/2 mutation carriers (BRCA-mut) were observed. No significant differences were detected in hormone receptor expression between the two populations. However, in the subgroup analysis according to menopausal status, a significantly lower ERα expression was found in pre-menopausal BRCA-mut compared to BRCA-wt patients (p=0.02) (figure 1). Regarding survival analysis, none of the examined hormone receptors had a significant prognostic role. However, a higher ERα/ERβ5nuclear ratio differently affected outcome according to BRCA status: positively in BRCA-wt cohort (HR 0.77; CI 0.61–0.96; p=0.019) and negatively in BRCA-mut cohort (HR 1.41; CI 1.06–1.87; p=0.020) (table 1). Finally, higher PR levels were associated with platinum sensitivity in the whole population (p=0.019).

Abstract 2022-RA-685-ESGO Figure 1
Abstract 2022-RA-685-ESGO Table 1

Survival analysis on BRCA-wt vs. BRCA mutated (n=207)

Conclusion This study suggests a potential role of estrogen-mediated pathways in BRCA1/2-associated HGSOC tumorigenesis, revealing a possible therapeutic potential of targeting this interaction.

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