title: Comparative analysis of breast cancer recurrence risk for patients receiving or not receiving adjuvant cyclophosphamide, methotrexate, fluorouracil (CMF). Data supporting the occurrence of 'cures'.
abstract: OBJECTIVE
  To comparatively analyse the risk of recurrence at given times after surgery for breast cancer patients receiving or not receiving adjuvant CMF.
  
  
  METHODS
  A total of 1452 node positive patients, who entered controlled clinical trials carried out at the Milan Cancer Institute and underwent radical or modified radical mastectomy for operable breast cancer, were examined. In 575 cases no further treatment was performed, whereas 877 pts were given 6 or 12 courses of adjuvant Cyclophosphamide, Methotrexate, Fluorouracil (CMF). The recurrence risk was estimated by the event-specific hazard rate for first failure and distant metastases, and, following Efron, hazard rates were fitted by logistic regression models.
  
  
  RESULTS
  The hazard rate for first failure and distant metastases showed a double peaked pattern for both treated patients and controls, with a first major peak at about 18-24 months from surgery (early metastases), a second minor peak at the 5th-6th year, and a tapered plateau-like tail extending over 10 years from surgery (late metastases). As expected, the recurrence risk of CMF treated patients was lower than the corresponding risk of patients undergoing surgery only. However, the difference was highly evident for early recurrences, while it declined and disappeared afterwards.
  
  
  CONCLUSIONS
  Our findings confirm previous reports on patients not receiving adjuvant chemotherapy, suggesting that the recurrence risk for operable breast cancer has a multipeak pattern. As far as CMF treated patients are concerned, the unchanged peak timing together with the early recurrence risk reduction in comparison to controls are much more consistent with the real nonappearance of some early recurrences (putatively 'cured' patients) than with the delay in their manifestation. As late relapsing patients seem to have at most marginal benefits from adjuvant CMF, ways to recognize patients doomed to have late recurrence and new ways for treating micrometastases resulting in late recurrences are required.
authors.affiliation: Division of Medical Oncology, Istituto Nazionale Tumori, Milano, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Demicheli
authors.forename: R
authors.initials: R
authors.lastname: Miceli
authors.forename: C
authors.initials: C
authors.lastname: Brambilla
authors.forename: L
authors.initials: L
authors.lastname: Ferrari
authors.forename: A
authors.initials: A
authors.lastname: Moliterni
authors.forename: M
authors.initials: M
authors.lastname: Zambetti
authors.forename: P
authors.initials: P
authors.lastname: Valagussa
authors.forename: G
authors.initials: G
authors.lastname: Bonadonna
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D015409:Mastectomy, Radical; D008727:Methotrexate / Q000627:therapeutic use; D012008:Recurrence; D012189:Retrospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D015996:Survival Rate; D013997:Time Factors
chemical_list: D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate