Outcome of neoadjuvant chemotherapy in BRCA1/2 mutation positive women with advanced stage Müllerian cancer

abstract

Highlights

• •Patients with germline BRCA mutations had improved outcomes with NAC compared to patients with unknown BRCA status.
• •The outcomes of NAC in BRCA mutation positive patients were more favorable than the outcomes reported in the literature.
• •This is the first study evaluating the outcome of NAC in BRCA mutation positive patients with advanced-stage mullerian cancer.

Objectives

To investigate whether patients with germline BRCA1/2 mutations who received neoadjuvant chemotherapy (NAC) for advanced stage Mullerian cancer (MC) have an improved outcome compared to patients who did not undergo genetic testing.

Methods

Three hundred and two patients who received NAC for stage III-IV MC were identified from a multi-institutional study involving Cleveland Clinic and Brigham and Women’s Hospital for 2000–2014 and 2010–2014 respectively. Patients were divided into 3 cohorts: patients with germline BRCA 1/2 mutations (BRCA_mut+; N = 30), patients with no genetic testing (BRCA_unk; N = 166) and patients with negative genetic testing (BRCA mut-, N = 106).

Results

There were no differences in the clinical characteristics and rates of complete cytoreduction and bowel resection between the three groups. BRCA_mut + had longer PFS compared to BRCA_unk and BRCA_mut- (19.1 vs. 15.1 vs. 15.7 months respectively. However, this difference was not statistically significant (p = 0.48). Patients with BRCA 2 mutation had non-significant trend toward longer PFS compared to patients with unknown BRCA or BRCA 1 mutation (20.2 vs. 15.1 vs. 14.8 months respectively, p = 0.58). BRCA-mut + and BRCA_mut-had longer overall survivals (OS) compared to BRCA_unk patients (50.5 vs. 54.1 vs. 36.5 months respectively, p = 0.009). In multivariable analyses, controlling for age, stage and complete cytoreduction, BRCA_mut_unk was associated with worse PFS (HR 1.44, 95% CI 1.01-2.05, p = 0.045) and OS (HR 2.67, 95% CI 1.33-5.36, p = 0.006).

Conclusions

Patients with germline BRCA mutations had improved outcomes with NAC compared to patients with unknown BRCA status. These outcomes were more favorable compared to the outcome of NAC in prior studies.