title: Pathological response and circulating tumor cell count identifies treated HER2+ inflammatory breast cancer patients with excellent prognosis: BEVERLY-2 survival data.
abstract: OBJECTIVE
  The BEVERLY-2 single-arm phase II trial assessed the efficacy and safety of combining neoadjuvant chemotherapy with bevacizumab and trastuzumab for the treatment of HER2-positive inflammatory breast cancer (IBC). Here, we report the results of a preplanned survival analysis at 3 years of follow-up, along with the association between outcome and circulating biomarkers and pathologic complete response (pCR).
  
  
  METHODS
  Patients received fluorouracil, epirubicin, cyclophosphamide, and bevacizumab (cycles 1-4) and docetaxel, trastuzumab, and bevacizumab (cycles 5-8) before surgery, followed by trastuzumab and bevacizumab for 30 weeks after surgery. Circulating tumor cell (CTC) and endothelial cell (CEC) counts were assessed at baseline, cycle 5, preoperative, postoperative, and at 1 year.
  
  
  RESULTS
  Fifty-two patients were included. The 3-year disease-free survival (DFS) rate was 68% and overall survival (OS) rate was 90%. pCR (centrally reviewed) was strongly associated with 3-year DFS [80% and 53% in patients with/without pCR, respectively (P = 0.03)]. CTC detection also independently predicted 3-year DFS [81% vs. 43% for patients with <1 vs. ≥1 CTC/7.5 mL at baseline (P = 0.01)]. Patients with no CTCs detected at baseline and with pCR had a high 3-year DFS (95%). CEC changes during treatment had no prognostic value.
  
  
  CONCLUSIONS
  Our study suggests that the prognosis of IBC relies on more than the achievement of pCR and highlights the role of early hematogenous tumor dissemination as assessed by CTCs. Combining these two prognostic factors isolates a subgroup of IBC with excellent survival when treated with bevacizumab- and trastuzumab-containing regimens.
authors.affiliation: Institut Curie, Paris, France. Université Paris Descartes, Paris, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Pierga
authors.affiliation: Centre Paul Strauss, Strasbourg, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Petit
authors.affiliation: Centre François Baclesse, Caen, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Lévy
authors.affiliation: Centre Antoine Lacassagne, Nice, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Ferrero
authors.affiliation: Institut de Cancérologie de l'Ouest-René Gauducheau, Saint Herblain, France.
authors.forename: Mario
authors.initials: M
authors.lastname: Campone
authors.affiliation: APHP Tenon, Alliance pour la Recherche en Cancérologie, Paris, France. Institut Universitaire de Cancérologie-Paris VI, Sorbonne Université, Paris, France.
authors.forename: Joseph
authors.initials: J
authors.lastname: Gligorov
authors.affiliation: Institut Curie Hôpital René Huguenin, Saint-Cloud, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Lerebours
authors.affiliation: Institut Claudius Regaud, Toulouse, France.
authors.forename: Henri
authors.initials: H
authors.lastname: Roché
authors.affiliation: Centre Léon-Bérard, Lyon, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bachelot
authors.affiliation: Institut Paoli-Calmettes, Marseille, France. Aix-Marseille University, Marseille, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Charafe-Jauffret
authors.affiliation: Institut Oscar Lambret, Lille, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Bonneterre
authors.affiliation: Roche, Boulogne-Billancourt, France.
authors.forename: Juana
authors.initials: J
authors.lastname: Hernandez
authors.affiliation: Institut Curie, Paris, France.
authors.forename: François-Clément
authors.initials: FC
authors.lastname: Bidard
authors.affiliation: Institut Paoli-Calmettes, Marseille, France. Aix-Marseille University, Marseille, France. viensp@ipc.unicancer.fr.
authors.forename: Patrice
authors.initials: P
authors.lastname: Viens
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D003520:Cyclophosphamide / Q000627:therapeutic use; D000077143:Docetaxel; D015251:Epirubicin / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D058922:Inflammatory Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009360:Neoplastic Cells, Circulating / Q000187:drug effects*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015996:Survival Rate; D043823:Taxoids / Q000627:therapeutic use; D000068878:Trastuzumab / Q000627:therapeutic use*
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D000068258:Bevacizumab; D014408:Biomarkers, Tumor; D003520:Cyclophosphamide; D000077143:Docetaxel; D015251:Epirubicin; D005472:Fluorouracil; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; C508053:ERBB2 protein, human