title: Response to neo-adjuvant chemotherapy in women with BRCA1-positive breast cancers.
abstract: OBJECTIVE
  There have been no studies to date which look at the relative effectiveness of different regimens of chemotherapy in women who have breast cancer and who carry a BRCA1 germ-line mutation. We wished to compare rates of response to neo-adjuvant chemotherapy in BRCA1 mutation carriers and non-carrier controls.
  
  
  METHODS
  From a registry of 3,479 patients, we identified 44 Polish women who carried a BRCA1 founder mutation and who had been treated with neo-adjuvant chemotherapy for breast cancer, and 41 age- and hospital-matched controls.
  
  
  RESULTS
  35 of the 44 BRCA1 mutation carriers (80%) experienced a partial or complete response to neo-adjuvant chemotherapy, compared to 39 of the 41 (95%) non-carriers (P=0.05). In the hereditary subgroup, response rates differed depending on whether or not a taxane (docetaxel) was given. Six of the 15 BRCA1 carrier women given docetaxel with doxorubicin responded (complete or partial), compared to 29 of 29 given other (DNA-damaging) therapies (P=0.001). Among the non-carriers, the rates of response to the two categories of chemotherapy were similar.
  
  
  CONCLUSIONS
  Breast cancers among BRCA1 carriers frequently do not exhibit sensitivity to docetaxel in the neo-adjuvant setting. It is likely that normal BRCA1 is required for clinical response to mitotic spindle poisons.
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
authors.forename: T
authors.initials: T
authors.lastname: Byrski
authors.forename: J
authors.initials: J
authors.lastname: Gronwald
authors.forename: T
authors.initials: T
authors.lastname: Huzarski
authors.forename: E
authors.initials: E
authors.lastname: Grzybowska
authors.forename: M
authors.initials: M
authors.lastname: Budryk
authors.forename: M
authors.initials: M
authors.lastname: Stawicka
authors.forename: T
authors.initials: T
authors.lastname: Mierzwa
authors.forename: M
authors.initials: M
authors.lastname: Szwiec
authors.forename: R
authors.initials: R
authors.lastname: Wiśniowski
authors.forename: M
authors.initials: M
authors.lastname: Siolek
authors.forename: S A
authors.initials: SA
authors.lastname: Narod
authors.forename: J
authors.initials: J
authors.lastname: Lubinski
mesh_terms: D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D017024:Chemotherapy, Adjuvant; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D018579:Patient Selection; D011044:Poland; D012042:Registries; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D050257:Tubulin Modulators / Q000008:administration & dosage
chemical_list: D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D043823:Taxoids; D050257:Tubulin Modulators; D000077143:Docetaxel; D004317:Doxorubicin