title: Effects of a treatment gap during adjuvant chemotherapy in node-positive breast cancer: results of International Breast Cancer Study Group (IBCSG) Trials 13-93 and 14-93.
abstract: BACKGROUND
  The International Breast Cancer Study Group (IBCSG) conducted two complementary randomized trials to assess whether a treatment-free gap during adjuvant chemotherapy influenced outcome.
  
  
  METHODS
  From 1993 to 1999, IBCSG Trials 13-93 and 14-93 enrolled 2215 premenopausal and postmenopausal women with axillary node-positive, operable breast cancer. All patients received cyclophosphamide (Cytoxan, C) plus either doxorubicin (Adriamycin, A) or epirubicin (E) for four courses followed immediately (No Gap) or after a 16-week delay (Gap) by classical cyclophosphamide, methotrexate, and fluorouracil (CMF) for three courses. The median follow-up was 7.7 years.
  
  
  RESULTS
  The Gap and No-Gap groups had similar disease-free survival (DFS) and overall survival (OS). No identified subgroup showed a statistically significant difference, but exploratory subgroup analysis noted a trend towards decreased DFS for Gap compared with No Gap for women with estrogen receptor (ER)-negative tumors not receiving tamoxifen, especially evident during the first 2 years.
  
  
  CONCLUSIONS
  A 16-week gap between adjuvant AC/EC and CMF provided no benefit and may have increased early recurrence rates in patients with ER-negative tumors.
authors.affiliation: Division of Medical Oncology, European Institute of Oncology, Milan, Italy. marco.colleoni@ieo.it
authors.forename: Marco
authors.initials: M
authors.lastname: Colleoni
authors.forename: Shari
authors.initials: S
authors.lastname: Gelber
authors.forename: Edda
authors.initials: E
authors.lastname: Simoncini
authors.forename: Olivia
authors.initials: O
authors.lastname: Pagani
authors.forename: Richard D
authors.initials: RD
authors.lastname: Gelber
authors.forename: Karen N
authors.initials: KN
authors.lastname: Price
authors.forename: Monica
authors.initials: M
authors.lastname: Castiglione-Gertsch
authors.forename: Alan S
authors.initials: AS
authors.lastname: Coates
authors.forename: Aron
authors.initials: A
authors.lastname: Goldhirsch
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000473:pathology*; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D011960:Receptors, Estrogen / Q000378:metabolism; D013629:Tamoxifen / Q000627:therapeutic use
chemical_list: D018931:Antineoplastic Agents, Hormonal; D011960:Receptors, Estrogen; D013629:Tamoxifen; D015251:Epirubicin; D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate