title: Early start of adjuvant chemotherapy may improve treatment outcome for premenopausal breast cancer patients with tumors not expressing estrogen receptors. The International Breast Cancer Study Group.
abstract: OBJECTIVE
  The proper time to commence adjuvant chemotherapy after primary surgery for breast cancer is unknown. An analysis of the International (Ludwig) Breast Cancer Study Group (IBCSG) Trial V at a median follow-up of 11 years suggested that early initiation of adjuvant chemotherapy might improve outcome for premenopausal, node-positive patients whose tumors did not express any estrogen receptor (ER).
  
  
  METHODS
  We investigated the relationship between early initiation of adjuvant chemotherapy, ER status, and prognosis in 1,788 premenopausal, node-positive patients treated on IBCSG trials I, II, and VI. The disease-free survival for 599 patients (84 with ER-absent tumors) who commenced adjuvant chemotherapy within 20 days (early initiation) was compared with the disease-free survival for 1,189 patients (142 with ER-absent tumors) who started chemotherapy 21 to 86 days after surgery (conventional initiation). The median follow-up was 7.7 years.
  
  
  RESULTS
  Among patients with ER-absent tumors, the 10-year disease-free survival was 60% for the early initiation group compared with 34% for the conventional initiation group (226 patients; hazard ratio [HR], 0. 49; 95% confidence interval [CI], 0.33 to 0.72; P =.0003). This difference remained statistically significant in a Cox multiple regression analysis controlling for study group, number of positive nodes, tumor size, age, vessel invasion, and institution (HR, 0.60; 95% CI, 0.39 to 0.92; P =.019). Conversely, early initiation of chemotherapy did not significantly improve disease-free survival for patients with tumors expressing ER (1,562 patients; multiple regression HR, 0.93; 95% CI, 0.79 to 1.10; P =.40).
  
  
  CONCLUSIONS
  In premenopausal patients with ER-absent tumors, early initiation of systemic chemotherapy after primary surgery might improve outcome. Further confirmatory studies are required before any widespread modification of current clinical practice. In premenopausal patients with tumors expressing some ER, gains from early initiation are unlikely to be clinically significant.
authors.affiliation: European Institute of Oncology, Milan, Italy. marco.colleoni@ieo.it
authors.forename: M
authors.initials: M
authors.lastname: Colleoni
authors.forename: M
authors.initials: M
authors.lastname: Bonetti
authors.forename: A S
authors.initials: AS
authors.lastname: Coates
authors.forename: M
authors.initials: M
authors.lastname: Castiglione-Gertsch
authors.forename: R D
authors.initials: RD
authors.lastname: Gelber
authors.forename: K
authors.initials: K
authors.lastname: Price
authors.forename: C M
authors.initials: CM
authors.lastname: Rudenstam
authors.forename: J
authors.initials: J
authors.lastname: Lindtner
authors.forename: J
authors.initials: J
authors.lastname: Collins
authors.forename: B
authors.initials: B
authors.lastname: Thürlimann
authors.forename: S
authors.initials: S
authors.lastname: Holmberg
authors.forename: A
authors.initials: A
authors.lastname: Veronesi
authors.forename: G
authors.initials: G
authors.lastname: Marini
authors.forename: A
authors.initials: A
authors.lastname: Goldhirsch
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D017697:Premenopause; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D011960:Receptors, Estrogen / Q000096:biosynthesis*; D016896:Treatment Outcome
chemical_list: D011960:Receptors, Estrogen; D002945:Cisplatin; D005472:Fluorouracil; D008727:Methotrexate