new restrospective: Chemosensitivity and Outcome of BRCA1- and BRCA2-Associated Ovarian Cancer Patie

Chemosensitivity and Outcome of BRCA1- and BRCA2-Associated Ovarian Cancer Patients After First-Line Chemotherapy Compared With Sporadic Ovarian Cancer Patients

Ann Oncol. 2011 Jan 12;22(6):1346-1352, PMLH Vencken, M Kriege, D Hoogwerf, S Beugelink, MEL van der Burg, MJ Hooning, EM Berns, A Jager, M Collée, CW Burger, C Seynaeve

In this retrospective cohort analysis comparing outcomes in patients with BRCA-associated vs sporadic ovarian cancer, response to first-line chemotherapy and survival were improved in patients with BRCA mutations.

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In this retrospective cohort analysis comparing outcomes in patients with BRCA-associated vs sporadic ovarian cancer, response to first-line chemotherapy and survival were improved in patients with BRCA mutations.

SUMMARY
An estimated 10% of women with epithelial ovarian cancer (EOC) carry a BRCA mutation. Studies comparing outcomes among women with BRCA-associated EOC vs sporadic EOC show that those with BRCA mutations have longer survival, with a single, but small, study available suggesting that this may be due to better response to standard-of-care first-line (platinum-based) chemotherapy. It is largely unknown how outcomes compare between women with BRCA2- vs BRCA1-associated EOC, although a few studies have reported better outcomes in those with BRCA2 mutations. In this retrospective analysis, Vencken et al compared response to primary therapy, which included first-line chemotherapy, and survival in patients with BRCA1-associated, BRCA2-associated, or sporadic EOC.

The investigators used the database of the Family Cancer Clinic of the Erasmus University Medical Center–Daniel den Hoed Cancer Center (Rotterdam, Netherlands) to identify patients who were diagnosed with EOC between January 1, 1980, and January 1, 2009, and who had a proven BRCA1 or BRCA2 mutation. These patients were matched 1:2 (by age at diagnosis and duration of diagnosis) with patients with sporadic EOC who were selected from the cancer registry of the institution or from the Rotterdam Comprehensive Cancer Center; any patients with a family history of breast or ovarian cancer were excluded from the sporadic EOC group. For study inclusion, a patient’s medical files needed to include essential data concerning patient and tumor characteristics, first-line chemotherapy administered as part of primary treatment, and follow-up.

The major study endpoints were response to first-line chemotherapy, progression-free survival (PFS), and overall survival (OS). A total of 334 patients (mean age at diagnosis, 52 years) met eligibility criteria and were included in the analysis. Within each patient group (BRCA1-positive EOC [n = 99], BRCA2-positive EOC [n = 13], and sporadic EOC [n = 222]), response to chemotherapy was measured overall (all treatment regimens combined) and separately for patients specifically treated with platinum with paclitaxel, platinum without paclitaxel, or a non–platinum based regimen. Treatment response was evaluated after the completion of first-line chemotherapy using World Health Organization (WHO) criteria, with differences in response among the patient groups tested with the Pearson chi-square test or Fisher’s exact test (for small numbers). PFS and OS were measured using the Kaplan–Meier survival method, with differences among the groups examined in a multivariate Cox proportional hazard regression model, adjusted for possible confounders.

Both BRCA patient groups had a better response after first-line chemotherapy compared with the sporadic EOC group. A complete response (CR) or no evidence of disease (NED) was achieved in 87% of patients (83/99) in the BRCA1 group vs 71% of patients (158/222) in the sporadic EOC group (P = .002), with progressive disease (PD) observed in 2 patients (2%) vs 34 patients (15%), respectively. CR/NED was achieved by 92% of patients (12/13) in the BRCA2 group, with no patients in this group having PD (P = .27).

Both BRCA patient groups also had significantly longer PFS and OS compared with the sporadic EOC group. Median PFS was 2.1 years (95% CI, 1.7–2.5; P = .006) for BRCA1 patients and 5.6 years (95% CI, 0.0–11.5; P = .008) for BRCA2 patients vs 1.3 years (95% CI, 1.1–1.5) for the sporadic EOC group. Median OS in the three patient groups was 5.9 years (95% CI, 4.7–7.0; P < .001), >10 years (95% CI not calculable; P = .002), and 2.9 years (95% CI, 2.2–3.5), respectively. At 5 and 10 years, both PFS and OS trended higher among patients with BRCA2 mutations than among those with BRCA1 mutations. Adjusted multivariate analysis showed that BRCA carriership was significantly associated with both improved PFS (BRCA1: hazard ratio [HR], 0.67; 95% CI, 0.50–0.89; BRCA2: HR, 0.45; 95% CI, 0.21–0.97) and improved OS (BRCA1: HR, 0.54; 95% CI, 0.39–0.74; BRCA2: HR, 0.38; 95% CI, 0.16–0.94).

Although retrospective, this study is the first to compare first-line chemotherapy response and survival in patients with BRCA1-associated, BRCA2-associated, or sporadic EOC. In this study, carriers of the BRCA mutation had a better chemotherapy response and longer survival than patients with sporadic EOC. The most favorable outcomes were seen in patients with BRCA2-associated EOC, although conclusions about these findings must be made with caution due to the small number of patients in the BRCA2 group.

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