title: Comparative benefit from small tumour size and adjuvant chemotherapy: clues for explaining breast cancer mortality decline.
abstract: BACKGROUND
  Breast cancer mortality steadily declined from the 1990s and this has been attributed to early detection and/or to improvements in therapy. Which of those two has had the greater impact is a subject of contention.
  
  
  METHODS
  A database of 386 patients, enrolled in a randomized clinical trial on the effect of adjuvant chemotherapy (CMF), was analysed. The probabilities of recurrence and death were estimated by the Fine and Gray's model and by the Cox model. Time dependent covariate and interaction effects were investigated by additive models. Absolute risk reductions (ARR) related to adjuvant treatment or to tumour size [diameter ≤ 2 cm (T1) or >2 cm (T2/T3)] were estimated.
  
  
  RESULTS
  CMF-related reduction in recurrence emerges early, reaches a maximum level at 3 years and persists at a constant level thereafter. Tumour-size-related recurrence reduction, after a maximum at 3 years, displays a progressive regular reduction approaching zero. Patients with any tumour size, when given CMF, exhibit mortality reduction that displays an early regular increase and continues to a persistent plateau. In contrast, tumour-size-related mortality reduction reaches a maximum at 5-7 years and then regularly drops to very low values for patients of both trial arms.
  
  
  CONCLUSIONS
  Findings reveal that there is a different time-dependent benefit from chemotherapy and from smaller tumour size at diagnosis. The benefit from adjuvant chemotherapy is long-lasting for patients with any tumour size while the early benefit of diagnosing smaller tumours substantially decreases afterwards. Treatment improvements have probably had greater impact on the mortality reduction than mammography screening.
authors.affiliation: Scientific Directorate, Fondazione IRCCS Istituto Nazionale Tumori, Via Venezian 1, 20133 Milano, Italy. demicheliromano@istitutotumori.mi.it.
authors.forename: Romano
authors.initials: R
authors.lastname: Demicheli
authors.forename: Federico
authors.initials: F
authors.lastname: Ambrogi
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage* / Q000627:therapeutic use; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis
chemical_list: D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate