title: Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer.
abstract: BACKGROUND
  No single standard treatment exists for patients with small, node-negative, human epidermal growth factor receptor type 2 (HER2)-positive breast cancers, because most of these patients have been ineligible for the pivotal trials of adjuvant trastuzumab.
  
  
  METHODS
  We performed an uncontrolled, single-group, multicenter, investigator-initiated study of adjuvant paclitaxel and trastuzumab in 406 patients with tumors measuring up to 3 cm in greatest dimension. Patients received weekly treatment with paclitaxel and trastuzumab for 12 weeks, followed by 9 months of trastuzumab monotherapy. The primary end point was survival free from invasive disease.
  
  
  RESULTS
  The median follow-up period was 4.0 years. The 3-year rate of survival free from invasive disease was 98.7% (95% confidence interval [CI], 97.6 to 99.8). Among the 12 relapses seen, 2 were due to distant metastatic breast cancer. Excluding contralateral HER2-negative breast cancers and nonbreast cancers, 7 disease-specific events were noted. A total of 13 patients (3.2%; 95% CI, 1.7 to 5.4) reported at least one episode of grade 3 neuropathy, and 2 had symptomatic congestive heart failure (0.5%; 95% CI, 0.1 to 1.8), both of whom had normalization of the left ventricular ejection fraction after discontinuation of trastuzumab. A total of 13 patients had significant asymptomatic declines in ejection fraction (3.2%; 95% CI, 1.7 to 5.4), as defined by the study, but 11 of these patients were able to resume trastuzumab therapy after a brief interruption.
  
  
  CONCLUSIONS
  Among women with predominantly stage I HER2-positive breast cancer, treatment with adjuvant paclitaxel plus trastuzumab was associated with a risk of early recurrence of about 2%; 6% of patients withdrew from the study because of protocol-specified adverse events. (Funded by Genentech; ClinicalTrials.gov number, NCT00542451.).
authors.affiliation: From the Departments of Medical Oncology (S.M.T., B.A.O., A.H.P., I.E.K., H.J.B., E.P.W.) and Biostatistics and Computation Biology (W.T.B., H.G.), Dana-Farber Cancer Institute, and Department of Hematology-Oncology, Massachusetts General Hospital (B.M.) - both in Boston; Breast Cancer Medicine Service, Department of Medicine, Solid Tumor Division, Memorial Sloan Kettering Cancer Center, and Department of Medicine, Weill Cornell Medical Center, New York (C.T.D., C.A.H.), and Department of Medical Oncology, Hofstra North Shore-LIJ School of Medicine, New Hyde Park (I.S.) - all in New York; Sarah Cannon Cancer Center, Department of Medical Oncology, Nashville (D.A.Y.); Department of Medicine, Division of Medical Oncology, Duke Cancer Institute, Durham (P.K.M.), and Department of Medical Oncology, University of North Carolina, Chapel Hill (L.A.C.) - both in North Carolina; Cardinal Bernardin Cancer Center, Department of Medicine, Division of Hematology-Oncology, Loyola University Chicago Stritch School of Medicine, Maywood, IL (K.S.A.); Comprehensive Cancer Center, Department of Medicine, Division of Oncology, University of California, San Francisco, San Francisco (H.S.R.); Department of Medical Oncology, Washington University in St. Louis, St. Louis (M.E.); and Johns Hopkins Kimmel Cancer Center, Department of Oncology, Baltimore (A.C.W.).
authors.forename: Sara M
authors.initials: SM
authors.lastname: Tolaney
authors.forename: William T
authors.initials: WT
authors.lastname: Barry
authors.forename: Chau T
authors.initials: CT
authors.lastname: Dang
authors.forename: Denise A
authors.initials: DA
authors.lastname: Yardley
authors.forename: Beverly
authors.initials: B
authors.lastname: Moy
authors.forename: P Kelly
authors.initials: PK
authors.lastname: Marcom
authors.forename: Kathy S
authors.initials: KS
authors.lastname: Albain
authors.forename: Hope S
authors.initials: HS
authors.lastname: Rugo
authors.forename: Matthew
authors.initials: M
authors.lastname: Ellis
authors.forename: Iuliana
authors.initials: I
authors.lastname: Shapira
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Wolff
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Carey
authors.forename: Beth A
authors.initials: BA
authors.lastname: Overmoyer
authors.forename: Ann H
authors.initials: AH
authors.lastname: Partridge
authors.forename: Hao
authors.initials: H
authors.lastname: Guo
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Hudis
authors.forename: Ian E
authors.initials: IE
authors.lastname: Krop
authors.forename: Harold J
authors.initials: HJ
authors.lastname: Burstein
authors.forename: Eric P
authors.initials: EP
authors.lastname: Winer
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D011878:Radiotherapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000276:immunology; D015996:Survival Rate; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human