title: The efficacy of taxane chemotherapy for metastatic breast cancer in BRCA1 and BRCA2 mutation carriers.
abstract: BACKGROUND
  We assessed the efficacy of taxane chemotherapy in BRCA1- and BRCA2-associated patients compared with sporadic metastatic breast cancer patients.
  
  
  METHODS
  Response rates (RRs) to and progression-free survival (PFS) after taxane chemotherapy of 35 BRCA1-associated and 13 BRCA2-associated metastatic breast cancer patients were compared with those outcomes in 95 matched (1:2) sporadic patients. Matching was performed for age at and year of diagnosis of primary breast cancer, year of metastatic disease, and line of therapy (first vs second or third).
  
  
  RESULTS
  Among BRCA1-associated patients, the RR was worse (objective response [OR], 23% vs 38%; progressive disease [PD], 60% vs 19%; P < 0.001); and the median PFS shorter (2.2 vs 4.9 months; P = 0.04) compared with sporadic patients. In the subgroup of hormone receptor (HRec)-negative patients, BRCA1-associated patients (n = 20) had a worse RR (OR, 20% vs 42%, respectively; PD, 70% vs 26%, respectively; P = 0.03) and a shorter PFS (1.8 vs 3.8 months; P = 0.004) compared with sporadic patients (n = 19). These outcomes in HRec-positive patients were similar in BRCA1-associated (n = 11) and sporadic (n = 61) patients (OR, 36% vs 38%; PD, 28% vs 20%; median PFS, both 5.7 months). In BRCA2-associated patients, who were mainly HRec-positive, the OR was higher than in sporadic patients (89% vs 38%, respectively; P = 0.02), whereas the median PFS was not significantly different (7.1 vs 5.7 months, respectively).
  
  
  CONCLUSIONS
  BRCA1-associated, HRec-negative metastatic breast cancer patients were less sensitive to taxane chemotherapy than sporadic HRec-negative patients. HRec-positive BRCA1- and BRCA2-associated patients had a sensitivity to taxane chemotherapy similar to that of sporadic patients.
authors.affiliation: Family Cancer Clinic, Department of Medical Oncology, Erasmus MC-Daniel den Hoed Cancer Centre, Rotterdam, Netherlands. a.kriege@erasmusmc.nl
authors.forename: Mieke
authors.initials: M
authors.lastname: Kriege
authors.forename: Agnes
authors.initials: A
authors.lastname: Jager
authors.forename: Maartje J
authors.initials: MJ
authors.lastname: Hooning
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Huijskens
authors.forename: Jannet
authors.initials: J
authors.lastname: Blom
authors.forename: Carolien H M
authors.initials: CH
authors.lastname: van Deurzen
authors.forename: Marijke
authors.initials: M
authors.lastname: Bontenbal
authors.forename: J Margriet
authors.initials: JM
authors.lastname: Collee
authors.forename: Marian B E
authors.initials: MB
authors.lastname: Menke-Pluijmers
authors.forename: John W M
authors.initials: JW
authors.lastname: Martens
authors.forename: Caroline
authors.initials: C
authors.lastname: Seynaeve
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary*; D001952:Bridged-Ring Compounds / Q000627:therapeutic use*; D016022:Case-Control Studies; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005820:Genetic Testing; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010597:Pharmacogenetics; D011379:Prognosis; D011960:Receptors, Estrogen / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics; D012189:Retrospective Studies; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D001952:Bridged-Ring Compounds; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D043823:Taxoids; C080625:taxane