BRCA mutational status, initial disease presentation, and clinical outcome in high-grade serous advanced ovarian cancer: a multicenter study

Abstract

Background: In the last decades, there have been several efforts to clarify the role of BRCA mutational status in women with advanced ovarian cancer, demonstrating its role in cancer development, as well as the prognostic significance of BRCA genotype.

Objective: Our aim is to evaluate the correlation between BRCA mutational status and disease presentation in a large series of advanced high-grade serous ovarian cancer patients.

Study design: This is a retrospective multicenter study including a consecutive series of newly diagnosed high-grade serous ovarian cancer patients with International Federation of Gynecology and Obstetrics stage IIIC-IV disease, at least 18 months of follow-up time, and tested for BRCA 1/2 germline mutation status. Disease presentation was analyzed using the following variables: laparoscopic predictive index value, incidence of bulky lymph nodes, and ovarian masses. Progression-free survival was defined as the months elapsed from initial diagnosis (staging laparoscopy) and recurrent disease or last follow-up.

Results: In all, 324 high-grade serous ovarian cancer patients received BRCA testing, and 273 fulfilled inclusion criteria. BRCA1/2 germline mutations were observed in 107 women (39.2%). No differences were documented according to BRCA mutation status in terms of International Federation of Gynecology and Obstetrics stage, CA125 levels, or presence of ascites. In patients with BRCA1/2 mutations we observed a higher incidence of peritoneal spread without ovarian mass (25.2% vs 13.9%; P value = .018) and of bulky lymph nodes (30.8% vs 17.5%; P value = .010) compared with women showing BRCA1/2 wild type genotype. Furthermore, women with BRCA1/2 mutations showed high peritoneal tumor load (laparoscopic predictive index value ≥8; 42.1% vs 27.1%; P value = .016) more frequently. Focusing on survival, no differences in term of median progression-free survival were observed among women treated with primary debulking surgery and neoadjuvant chemotherapy in the group of patients with BRCA1/2 mutations (P value = .268). On the other hand, in women showing BRCA wild type genotype, median progression-free survival after primary debulking surgery was 8 months longer compared with patients treated with neoadjuvant chemotherapy approach (26 vs 18 months; P value = .003).

Conclusion: Women with BRCA1/2 mutations show at diagnosis higher peritoneal tumor load and increased frequency of bulky lymph nodes compared to patients without germline BRCA mutations. Primary debulking surgery seems to ensure a longer progression-free survival in women with BRCA wild type genotype compared to neoadjuvant chemotherapy. BRCA testing might be a reliable tool to personalize treatment in patients with high-grade serous ovarian cancer, thus giving novel points of discussion to the ongoing debate regarding the best initial treatment approach.

Keywords: BRCA1/2 mutational status; advanced ovarian cancer; high-grade serous; laparoscopic predictive index value; neoadjuvant chemotherapy; primary debulking surgery.