title: Six cycles of doxorubicin and cyclophosphamide or Paclitaxel are not superior to four cycles as adjuvant chemotherapy for breast cancer in women with zero to three positive axillary nodes: Cancer and Leukemia Group B 40101.
abstract: OBJECTIVE
  The ideal duration of adjuvant chemotherapy for patients with lower risk primary breast cancer is not known. Cancer and Leukemia Group B trial 40101 was conducted using a phase III factorial design to define whether six cycles of a chemotherapy regimen are superior to four cycles. We also sought to determine whether paclitaxel (T) is as efficacious as doxorubicin/cyclophosphamide (AC), but with reduced toxicity.
  
  
  METHODS
  Between 2002 and 2008, the study enrolled women with operable breast cancer and zero to three positive nodes. Patients were randomly assigned to either four or six cycles of either AC or T. Study stratifiers were estrogen receptor/progesterone receptor (ER/PgR), human epidermal growth factor receptor 2 (HER2), and menopausal status. After 2003, all treatment was administered in dose-dense fashion. The primary efficacy end point was relapse-free survival (RFS).
  
  
  RESULTS
  A total of 3,171 patients were enrolled; 94% were node-negative and 6% had one to three positive nodes. At a median follow-up of 5.3 years, the 4-year RFS was 90.9% and 91.8% for six and four cycles, respectively. The adjusted hazard ratio (HR) of six to four cycles regarding RFS was 1.03 (95% CI, 0.84 to 1.28; P=.77). The 4-year OS was 95.3% and 96.3% for six and four cycles, respectively, with an HR of six to four cycles of 1.12 (95% CI, 0.84 to 1.49; P=.44). There was no interaction between treatment duration and chemotherapy regimen, ER/PgR, or HER2 status on RFS or OS.
  
  
  CONCLUSIONS
  For women with resected primary breast cancer and zero to three positive nodes, we found no evidence that extending chemotherapy regimens of AC or single-agent T from four to six cycles improves clinical outcome.
authors: Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215, USA. Lawrence_Shulman@dfci.harvard.edu
authors: Lawrence N
authors: LN
authors: Shulman
authors: Constance T
authors: CT
authors: Cirrincione
authors: Donald A
authors: DA
authors: Berry
authors: Heather P
authors: HP
authors: Becker
authors: Edith A
authors: EA
authors: Perez
authors: Ruth
authors: R
authors: O'Regan
authors: Silvana
authors: S
authors: Martino
authors: James N
authors: JN
authors: Atkins
authors: Erica
authors: E
authors: Mayer
authors: Charles J
authors: CJ
authors: Schneider
authors: Gretchen
authors: G
authors: Kimmick
authors: Larry
authors: L
authors: Norton
authors: Hyman
authors: H
authors: Muss
authors: Eric P
authors: EP
authors: Winer
authors: Clifford
authors: C
authors: Hudis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D012307:Risk Factors
chemical_list: D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel