title: Long-term survival of advanced triple-negative breast cancers with a dose-intense cyclophosphamide/anthracycline neoadjuvant regimen.
abstract: BACKGROUND
  Triple-negative (TN) breast cancers exhibit major initial responses to neoadjuvant chemotherapy, but generally have a poor outcome. Because of the lack of validated drug targets, chemotherapy remains an important therapeutic tool in these cancers.
  
  
  METHODS
  We report the survival of two consecutive series of 267 locally advanced breast cancers (LABC) treated with two different neoadjuvant regimens, either a dose-dense and dose-intense cyclophosphamide-anthracycline (AC) association (historically called SIM) or a conventional sequential association of cyclophosphamide and anthracycline, followed by taxanes (EC-T). We compared pathological responses and survival rates of these two groups and studied their association with tumours features.
  
  
  RESULTS
  Although the two regimens showed equivalent pathological complete response (pCR) in the whole population (16 and 12%), the SIM regimen yielded a non-statistically higher pCR rate than EC-T (48% vs 24%, P=0.087) in TN tumours. In the SIM protocol, DFS was statistically higher for TN than for non-TN patients (P=0.019), although we showed that the TN status was associated with an increased initial risk of recurrence in both regimens. This effect gradually decreased and after 2 years, TN was associated with a significantly decreased likelihood of relapse in SIM-treated LABC (hazard ratio (HR)=0.25 (95% CI: 0.07-0.86), P=0.028).
  
  
  CONCLUSIONS
  AC dose intensification treatment is associated with a very favourable long-term survival rate in TN breast cancers. These observations call for a prospective assessment of such dose-intense AC-based regimens in locally advanced TN tumours.
authors.affiliation: AP-HP, Hôpital Saint-Louis, Breast Disease Unit, University Paris Diderot, Paris 75475, France.
authors.forename: S
authors.initials: S
authors.lastname: Giacchetti
authors.affiliation: AP-HP, Hôpital Saint-Louis, Biostatistic Department, Paris 75475, France.
authors.forename: R
authors.initials: R
authors.lastname: Porcher
authors.affiliation: 1] AP-HP, Hôpital Saint-Louis, Molecular Biology Department, Paris 75475, France [2] INSERM/CNRS/University Paris Diderot UMR 944/7212, Paris 75475, France.
authors.forename: J
authors.initials: J
authors.lastname: Lehmann-Che
authors.affiliation: AP-HP, Hôpital Saint-Louis, Breast Disease Unit, University Paris Diderot, Paris 75475, France.
authors.forename: A-S
authors.initials: AS
authors.lastname: Hamy
authors.affiliation: 1] AP-HP, Hôpital Saint-Louis, Pathology Department, Paris 75475, France [2] University Paris Diderot, UMR-S-728 INSERM, Paris 75475, France.
authors.forename: A
authors.initials: A
authors.lastname: de Roquancourt
authors.affiliation: AP-HP, Hôpital Saint-Louis, Breast Disease Unit, University Paris Diderot, Paris 75475, France.
authors.forename: C
authors.initials: C
authors.lastname: Cuvier
authors.affiliation: AP-HP, Hôpital Saint-Louis, Breast Disease Unit, University Paris Diderot, Paris 75475, France.
authors.forename: P-H
authors.initials: PH
authors.lastname: Cottu
authors.affiliation: 1] AP-HP, Hôpital Saint-Louis, Pathology Department, Paris 75475, France [2] University Paris Diderot, UMR-S-728 INSERM, Paris 75475, France.
authors.forename: P
authors.initials: P
authors.lastname: Bertheau
authors.affiliation: AP-HP, Hôpital Saint-Louis, Radiology Department, Paris 75475, France.
authors.forename: M
authors.initials: M
authors.lastname: Albiter
authors.affiliation: 1] AP-HP, Hôpital Saint-Louis, Pathology Department, Paris 75475, France [2] University Paris Diderot, UMR-S-728 INSERM, Paris 75475, France.
authors.forename: F
authors.initials: F
authors.lastname: Bouhidel
authors.affiliation: AP-HP, Hôpital Saint-Louis, Breast Disease Unit, University Paris Diderot, Paris 75475, France.
authors.forename: F
authors.initials: F
authors.lastname: Coussy
authors.affiliation: AP-HP, Hôpital Saint-Louis, Breast Disease Unit, University Paris Diderot, Paris 75475, France.
authors.forename: J-M
authors.initials: JM
authors.lastname: Extra
authors.affiliation: AP-HP, Hôpital Saint-Louis, Breast Disease Unit, University Paris Diderot, Paris 75475, France.
authors.forename: M
authors.initials: M
authors.lastname: Marty
authors.affiliation: 1] AP-HP, Hôpital Saint-Louis, Molecular Biology Department, Paris 75475, France [2] INSERM/CNRS/University Paris Diderot UMR 944/7212, Paris 75475, France.
authors.forename: H
authors.initials: H
authors.lastname: de Thé
authors.affiliation: AP-HP, Hôpital Saint-Louis, Breast Disease Unit, University Paris Diderot, Paris 75475, France.
authors.forename: M
authors.initials: M
authors.lastname: Espié
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D017741:Survivors; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D055815:Young Adult
chemical_list: D015251:Epirubicin; D003520:Cyclophosphamide