title: High efficacy of cisplatin neoadjuvant therapy in a prospective series of patients carrying BRCA1 germ-line mutation.
abstract: Development of malignancies in BRCA1 germ-line mutation carriers usually involves somatic inactivation of the remaining BRCA1 allele. This feature leads to a tumor-specific deficiency of double-strand DNA break repair and underlies pronounced sensitivity of BRCA1-driven cancers to cisplatin. BRCA1-specific activity of cisplatin has been repeatedly demonstrated in cell culture and animal experiments; however, corresponding clinical evidence remains limited. We applied neoadjuvant monotherapy by cisplatin (75-100 mg/m(2), 4-6 cycles) to six breast cancer patients carrying BRCA1 5382insC mutation. Pronounced reduction in tumor size was observed in all treated women. Three patients (T2N0M0, T4N2M0 and T4N2M0) showed pathologic complete response, two women (T4N0M0 and T2N1M0) had partial pathologic response, and one woman (T3N2M0) declined surgery. This study and available literature data suggest that cisplatin is a preferable option for systemic treatment of BRCA1-related hereditary breast cancer.
authors.affiliation: City Cancer Center, St.-Petersburg, 197758, Russia.
authors.forename: Vladimir M
authors.initials: VM
authors.lastname: Moiseyenko
authors.forename: Georgiy D
authors.initials: GD
authors.lastname: Dolmatov
authors.forename: Fedor V
authors.initials: FV
authors.lastname: Moiseyenko
authors.forename: Alexandr O
authors.initials: AO
authors.lastname: Ivantsov
authors.forename: Nikita M
authors.initials: NM
authors.lastname: Volkov
authors.forename: Vyacheslav A
authors.initials: VA
authors.lastname: Chubenko
authors.forename: Nuriniso Kh
authors.initials: NKh
authors.lastname: Abduloeva
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Bogdanov
authors.forename: Anna P
authors.initials: AP
authors.lastname: Sokolenko
authors.forename: Evgeny N
authors.initials: EN
authors.lastname: Imyanitov
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D002945:Cisplatin / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012074:Remission Induction
chemical_list: D000970:Antineoplastic Agents; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D002945:Cisplatin