title: Outcome of neoadjuvant chemotherapy in BRCA1/2 mutation positive women with advanced-stage Müllerian cancer.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Gynecologic Oncology, Ob/Gyn and Women's Health Institute, Cleveland Clinic, Cleveland, OH, USA. Electronic address: mahdih6281@gmail.com.
authors.forename: Haider
authors.initials: H
authors.lastname: Mahdi
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Gockley
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Esselen
authors.affiliation: Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Marquard
authors.affiliation: Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Nutter
authors.affiliation: Department of Anatomic Pathology, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Hinchcliff
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Neil
authors.initials: N
authors.lastname: Horowitz
authors.affiliation: Division of Gynecologic Oncology, Ob/Gyn and Women's Health Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Rose
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D065426:Cytoreduction Surgical Procedures; D018572:Disease-Free Survival; D005185:Fallopian Tube Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; 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 / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D010534:Peritoneal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents
keywords: Advanced-stage cancer of Müllerian origin; BRCA; Hereditary ovarian cancer; Neoadjuvant chemotherapy; Overall survival; Progression free survival