title: Breast cancer sensitivity to neoadjuvant therapy in BRCA1 and CHEK2 mutation carriers and non-carriers.
abstract: Breast carcinomas caused by inheritance of cancer-predisposing germ-line mutations have specific bioclinical features. This study aimed to analyze the efficacy of conventional cytotoxic treatment in BRCA1 and CHEK2 mutation carriers and non-carriers. The study included 415 Russian breast cancer patients aged 50 years or younger, who were subjected to various standard schemes of neoadjuvant therapy. The choice of therapy was done without the knowledge of the mutations status, because DNA testing was performed retrospectively using the archival tissue samples. 19 BRCA1 (4.6%) and 8 CHEK2 (1.9%) heterozygous genotypes were identified. BRCA1 mutation carriers achieved pathological complete response more frequently than non-carriers [6/19 (31.6%) vs. 46/388 (11.9%), p = 0.024]; this effect was limited to women treated by anthracycline-based therapy without taxanes [5/9 (55.6%) vs. 28/247 (11.3%), p = 0.002] and was not observed in any of 7 BRCA1 carriers receiving taxane-containing regimens. CHEK2 heterozygotes did not experience pathological complete response and showed lower frequency of objective clinical responses as compared to mutation non-carriers [4/8 (50%) vs. 333/388 (85.5%), p = 0.020]; the efficacy of neoadjuvant therapy was particularly poor in CHEK2 carriers receiving anthracyclines without taxanes. This study provides evidence for distinct sensitivity of BRCA1 and CHEK2 mutation-driven breast carcinomas to standard chemotherapeutic schemes.
authors.affiliation: Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Pesochny-2, 197758, Saint Petersburg, Russia.
authors.forename: Werner
authors.initials: W
authors.lastname: Pfeifer
authors.forename: Anna P
authors.initials: AP
authors.lastname: Sokolenko
authors.forename: Olga N
authors.initials: ON
authors.lastname: Potapova
authors.forename: Alexandr A
authors.initials: AA
authors.lastname: Bessonov
authors.forename: Alexandr O
authors.initials: AO
authors.lastname: Ivantsov
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Laptiev
authors.forename: Olga A
authors.initials: OA
authors.lastname: Zaitseva
authors.forename: Olga S
authors.initials: OS
authors.lastname: Yatsuk
authors.forename: Dmitry E
authors.initials: DE
authors.lastname: Matsko
authors.forename: Tatiana Yu
authors.initials: TY
authors.lastname: Semiglazova
authors.forename: Alexandr V
authors.initials: AV
authors.lastname: Togo
authors.forename: Evgeny N
authors.initials: EN
authors.lastname: Imyanitov
mesh_terms: D000328:Adult; D018943:Anthracyclines / Q000008:administration & dosage; D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D064447:Checkpoint Kinase 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D018943:Anthracyclines; D019313:BRCA1 Protein; D043823:Taxoids; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human