title: Weekly paclitaxel/carboplatin/trastuzumab therapy improves pathologic complete remission in aggressive HER2-positive breast cancers, especially in luminal-B subtype, compared with a once-every-3-weeks schedule.
abstract: BACKGROUND
  The efficacy and tolerability of two different schedules of paclitaxel, carboplatin, and trastuzumab (PCarH) for HER2-positive, locally aggressive (stage IIB-IIIC) breast cancers were evaluated in this phase II trial.
  
  
  METHODS
  Patients were randomly assigned to receive either weekly (12 doses over 16 weeks) or once-every-3-weeks (4 doses over 12 weeks) treatment. The primary endpoint was pathologic complete remission (pCR) in the breast and axilla. To detect an assumed 35% pCR absolute difference between the two schedules, a minimum of 26 assessable patients in each group was required (two-sided α = 0.05, β = 0.2).
  
  
  RESULTS
  A total of 56 patients were enrolled (weekly group, n = 29; every-3-weeks group, n = 27). In the intent-to-treat analysis, pCR in the breast/axilla were found in 31 patients (55%; 95% confidence interval [CI]: 41%-69%). Compared with the every-3-weeks schedule, the weekly administration achieved higher pCR (41% vs. 69%; p = .03). After adjustment for clinical and pathological factors, the weekly administration was more effective than the every-3-weeks schedule, with hazard ratio of 0.3 (95% CI: 0.1-0.9; p = .03). Interestingly, weekly administration resulted in high pCR rates in both luminal-B (HER2-positive) and ERBB2+ tumors (67% vs. 71%; p = .78), whereas luminal-B (HER2-positive) tumors benefited less from the every-3-weeks schedule compared with the ERBB2+ tumors (21% vs. 62%, p = .03). These results remain after multivariate adjustment, showing weekly administration was more effective in the luminal-B (HER2-positive) subgroup (p = .02) but not in the ERBB2+ subgroup (p = .50).
  
  
  CONCLUSIONS
  A more frequent administration might improve the possibility of eradicating invasive cancer in the breast and axilla, especially in the luminal-B (HER2-positive) subtype. Further studies to validate our findings are warranted.
authors: Department of Breast Surgery, Cancer Center and Cancer Institute, Shanghai Medical College, Fudan University, Shanghai, China.
authors: Ke-Da
authors: KD
authors: Yu
authors: Guang-Yu
authors: GY
authors: Liu
authors: Can-Ming
authors: CM
authors: Chen
authors: Jian-Wei
authors: JW
authors: Li
authors: Jiong
authors: J
authors: Wu
authors: Jin-Song
authors: JS
authors: Lu
authors: Zhen-Zhou
authors: ZZ
authors: Shen
authors: Zhi-Ming
authors: ZM
authors: Shao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology*; D016190:Carboplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D012074:Remission Induction; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D016190:Carboplatin; D003520:Cyclophosphamide; D005472:Fluorouracil; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
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