Outcome of neoadjuvant chemotherapy in BRCA1/2 mutation positive women with advanced-stage Müllerian cancer.
OBJECTIVES
To investigate whether patients with germline BRCA1/2 mutations who received neoadjuvant chemotherapy (NAC) for advanced-stage Müllerian 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 BRCA1/2 mutations (BRCA_mut+; N=30), patients with no genetic testing (BRCA_mut_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_mut_unk and BRCA_mut- (19.1 vs. 15.1 vs. 15.7months respectively. However, this difference was not statistically significant (p=0.48). Patients with BRCA2 mutation had non-significant trend toward longer PFS compared to patients with unknown BRCA or BRCA1 mutation (20.2 vs. 15.1 vs. 14.8months respectively, p=0.58). BRCA_mut+ and BRCA_mut- had longer overall survivals (OS) compared to BRCA_mut_unk patients (50.5 vs. 54.1 vs. 36.5months 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.
['Mahdi|Haider|H|', 'Gockley|Allison|A|', 'Esselen|Katherine|K|', 'Marquard|Jessica|J|', 'Nutter|Benjamin|B|', 'Yang|Bin|B|', 'Hinchcliff|Emily|E|', 'Horowitz|Neil|N|', 'Rose|Peter G|PG|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D000970:Antineoplastic Agents D017024:Chemotherapy, Adjuvant D065426:Cytoreduction Surgical Procedures D018572:Disease-Free Survival D005185:Fallopian Tube Neoplasms D005260:Female D019398:Genes, BRCA1 D024522:Genes, BRCA2 D005820:Genetic Testing D018095:Germ-Line Mutation D006801:Humans D008875:Middle Aged D020360:Neoadjuvant Therapy D009367:Neoplasm Staging D010051:Ovarian Neoplasms D010534:Peritoneal Neoplasms D012189:Retrospective Studies D015996:Survival Rate
Neoadjuvant chemotherapy BRCA Overall survival Advanced-stage cancer of Müllerian origin Hereditary ovarian cancer Progression free survival