title: Patients with Slowly Proliferative Early Breast Cancer Have Low Five-Year Recurrence Rates in a Phase III Adjuvant Trial of Capecitabine.
abstract: We conducted a randomized phase III study to determine whether patients with early breast cancer would benefit from the addition of capecitabine (X) to a standard regimen of doxorubicin (A) plus cyclophosphamide (C) followed by docetaxel (T).
  
  
  
  Treatment comprised eight cycles of AC→T (T dose: 100 mg/m(2) on day 1) or AC→XT (X dose: 825 mg/m(2) twice daily, days 1-14; T dose: 75 mg/m(2) on day 1). The primary endpoint was 5-year disease-free survival (DFS).
  
  
  
  Of 2,611 women, 1,304 were randomly assigned to receive AC→T and 1,307 to receive AC→XT. After a median follow-up of 5 years, the study failed to meet its primary endpoint [HR, 0.84; 95% confidence interval (CI), 0.67-1.05; P = 0.125]. A significant improvement in overall survival, a secondary endpoint, was seen with AC→XT versus AC→T (HR, 0.68; 95% CI, 0.51-0.92; P = 0.011). There were no unexpected adverse events. Of patients with estrogen receptor (ER)-positive/HER2-negative disease, 70% of whom were node-positive, 26% and 59% had tumors with a centrally assessed Ki-67 score of <10% or <20%, respectively, and only 17 (2%) and 53 (6%) DFS events, respectively, occurred in these groups at 7 years.
  
  
  
  The very low event rate in patients with ER-positive, low Ki-67 cancers, regardless of nodal status, strongly suggests that these patients should not be enrolled in adjuvant trials that assess 5-year DFS rates and that central Ki-67 analyses can identify these patients.
authors.affiliation: Texas Oncology Baylor-Sammons Cancer Center, US Oncology, Dallas, Texas. joyce.oshaughnessy@usoncology.com.
authors.forename: Joyce
authors.initials: J
authors.lastname: O'Shaughnessy
authors.affiliation: Genentech Inc., South San Francisco, California.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Koeppen
authors.affiliation: Genentech Inc., South San Francisco, California.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Genentech Inc., South San Francisco, California.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Lackner
authors.affiliation: Rocky Mountain Cancer Center, Denver, Colorado.
authors.forename: Devchand
authors.initials: D
authors.lastname: Paul
authors.affiliation: Texas Oncology-Plano East Cancer Center, US Oncology, Plano, Texas.
authors.forename: Christopher
authors.initials: C
authors.lastname: Stokoe
authors.affiliation: Texas Oncology Baylor-Sammons Cancer Center, US Oncology, Dallas, Texas.
authors.forename: John
authors.initials: J
authors.lastname: Pippen
authors.affiliation: Texas Oncology-The Breast Care Center of North Texas, US Oncology, Bedford, Texas.
authors.forename: Lea
authors.initials: L
authors.lastname: Krekow
authors.affiliation: Texas Oncology-Houston Memorial City, US Oncology, Houston, Texas.
authors.forename: Frankie Ann
authors.initials: FA
authors.lastname: Holmes
authors.affiliation: Texas Oncology-Tyler, US Oncology, Tyler, Texas.
authors.forename: Svetislava
authors.initials: S
authors.lastname: Vukelja
authors.affiliation: Arizona Oncology Associates, US Oncology, Sedona, Arizona.
authors.forename: Deborah
authors.initials: D
authors.lastname: Lindquist
authors.affiliation: Rocky Mountain Cancer Center, Denver, Colorado.
authors.forename: Scot
authors.initials: S
authors.lastname: Sedlacek
authors.affiliation: Texas Oncology-El Paso Cancer Treatment Center, US Oncology, El Paso, Texas.
authors.forename: Ragene
authors.initials: R
authors.lastname: Rivera
authors.affiliation: Arizona Oncology Associates, US Oncology, Tucson, Arizona.
authors.forename: Robert
authors.initials: R
authors.lastname: Brooks
authors.affiliation: Texas Oncology-Dallas Presbyterian Hospital, US Oncology, Dallas, Texas.
authors.forename: Kristi
authors.initials: K
authors.lastname: McIntyre
authors.affiliation: Hoffmann-La Roche Inc., Nutley, New Jersey.
authors.forename: Carrie
authors.initials: C
authors.lastname: Brownstein
authors.affiliation: CRO Koehler-eClinical, Freiburg, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Hoersch
authors.affiliation: Texas Oncology Baylor-Sammons Cancer Center, US Oncology, Dallas, Texas.
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Blum
authors.affiliation: US Oncology, The Woodlands, Texas.
authors.forename: Stephen
authors.initials: S
authors.lastname: Jones
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D000069287:Capecitabine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D000077143:Docetaxel; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D043823:Taxoids; D000077143:Docetaxel; D000069287:Capecitabine