Survival in epithelial ovarian cancer: a multivariate analysis incorporating BRCA mutation status and platinum sensitivity
ABSTRACT Patients with BRCA-associated ovarian cancer (OC) have a survival advantage over those with sporadic OC. To further explore this, we examined the impact of prognostic factors on disease-free survival (DFS) and overall survival (OS) in patients with known BRCA mutation status.
We reviewed stage III-IV OC patients treated at our institution between 1 December 1996 and 30 September 2006 and also tested on protocol for BRCA mutations. Impact on DFS and OS was determined by Kaplan-Meier analysis and a Cox proportional hazards model.
Of the 110 patients, 36 had deleterious BRCA mutations [BRCA (+)] and 74 were BRCA wild type [BRCA(-)]. Thirty-one of 36 (86%) BRCA (+) and 60 of 74 (81%) BRCA (-) patients were platinum sensitive (P = 0.60). Median OS was longer for BRCA (+) patients (not reached versus 67.8 months; P = 0.02), but DFS was similar (26.9 versus 24.0, P = 0.3). On multivariate analysis, OS correlated with primary platinum sensitivity [HR = 0.15; 95% CI (confidence interval) 0.06-0.34] and BRCA (+) mutation status (HR = 0.33; 95% CI 0.12-0.86).
BRCA mutation status predicted OS independent of primary platinum sensitivity, suggesting that underlying tumor biology contributes to disease outcome and may be worthy of consideration in future clinical trial design.
SourceAvailable from: Anna Myriam Perrone[Show abstract] [Hide abstract]
ABSTRACT: Ovarian cancer (OC) mostly arises sporadically, but a fraction of cases are associated with mutations in BRCA1 and BRCA2 genes. The presence of a BRCA mutation in OC patients has been suggested as a prognostic and predictive factor. In addition, the identification of asymptomatic carriers of such mutations offers an unprecedented opportunity for OC prevention. This review is aimed at exploring the current knowledge on epidemiological and molecular aspects of BRCA-associated OC predisposition, on pathology and clinical behavior of OC occurring in BRCA mutation carriers, and on the available options for managing asymptomatic carriers.BioMed Research International 07/2014; 2014:787143. DOI:10.1155/2014/787143 · 2.71 Impact Factor
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ABSTRACT: Objective. Predicting survival of patients with epithelial ovarian cancer (EOC) is based on prognosis of the population. Combining prognostic factors could facilitate survival prediction on the level of the individual patient. The aim of this study was to develop a prognostic model to predict five-year disease specific survival in patients with EOC, and to evaluate whether this would add to prediction based on prognosis of the population. Patients and methods. A retrospective cohort study was performed of all EOC patients treated with primary debulking and adjuvant chemotherapy or neo-adjuvant chemotherapy and interval debulking surgery in three gynaecological-oncologic centres between 1998 and 2010. Primary outcome was 5-year disease-specific survival. We developed a Cox proportional hazard model using the LASSO-method to select the best combination of characteristics from 12 potential predictors and to correct for overfitting. Performance of the model was expressed as calibration and discrimination (c-statistic). A nomogram was developed to increase the clinical applicability of the model. Results. Of 840 patients with EOC 462 (55%) died within 5 years due to the disease. A combination of FIGO stage, residual tumour after surgery, primary or interval surgery, histology, performance status, age, amount of ascites and a family history suggestive of breast/ovarian cancer best predicted 5-year survival. The final model showed accurate calibration and the c-statistic was 0.71 (95% CI 0.69-0.74). Conclusions. Five-year survival in all stage EOC patients can be predicted accurately using available characteristics. After external validation the model can be used for counselling of patients.Gynecologic Oncology 08/2014; 135(1). DOI:10.1016/j.ygyno.2014.07.099 · 3.69 Impact Factor
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ABSTRACT: Objective: The aim of this study was to explore BRCA mutation frequency and to evaluate its impact on prognosis of advanced-stage ovarian cancer patients treated with debulking surgery and platinum-based chemotherapy. Methods: Patients with advanced-stage epithelial ovarian cancer were enrolled in a prospective, single-center study from September 2008 to December 2011. All cases were screened for BRCA1 and BRCA2 gene mutations. Progression-free survival (PFS) was assessed between BRCA1/2 mutation carriers and BRCA1/2 wild-type patients. Results: One hundred seven patients were enrolled and screened for BRCA1 and BRCA2 mutations; 51.4% patients were positive for BRCA1/2 gene mutation, 63.6% of which carried a single Baltic mutation, and 98.2% of them had serous histology. Older age (hazard ratio [HR], 1.032; 95% confidence interval [CI], 1.010-1.055; P = 0.0047), nonoptimal cytoreduction (HR, 3.170; 95% CI, 1.986-5.060; P < 0.0001), and BRCA1/2 wild type (HR, 1.625 [1.003-2.632]; P = 0.0486) were significantly associated with shorter PFS in multivariate Cox regression analysis. Only the nonoptimal cytoreduction was a statistically significant risk factor for shorter overall survival (HR, 2.684; 95% CI, 1.264-5.701; P= 0.0102). Conclusions: Advanced ovarian cancer patients harboring BRCA1/2 mutation treated with debulking surgery and platinum-based adjuvant chemotherapy have a longer PFS.International Journal of Gynecological Cancer 10/2014; 24(8):1395-1400. DOI:10.1097/IGC.0000000000000247 · 1.95 Impact Factor