Circulating tumour cells and pathological complete response: independent prognostic factors in inflammatory breast cancer in a pooled analysis of two multicentre phase II trials (BEVERLY-1 and -2) of neoadjuvant chemotherapy combined with bevacizumab.
We present a pooled analysis of predictive and prognostic values of circulating tumour cells (CTC) and circulating endothelial cells (CEC) in two prospective trials of patients with inflammatory breast cancer (IBC) treated with neoadjuvant chemotherapy combined with neoadjuvant and adjuvant bevacizumab.



Nonmetastatic T4d patients were enrolled in two phase II multicentre trials, evaluating bevacizumab in combination with sequential neoadjuvant chemotherapy of four cycles of FEC followed by four cycles of docetaxel in HER2-negative tumour (BEVERLY-1) or docetaxel and trastuzumab in HER2-positive tumour (BEVERLY-2). CTC and CEC were detected in 7.5 and 4 ml of blood, respectively, with the CellSearch System.



From October 2008 to September 2010, 152 patients were included and 137 were evaluable for CTC and CEC. At baseline, 55 patients had detectable CTC (39%). After four cycles of chemotherapy, a dramatic drop in CTC to a rate of 9% was observed (P < 0.01). Pathological complete response (pCR) rate was 40%. No correlation was found between CTC or CEC levels and pCR rate. Median follow-up was 43 months. CTC detection (≥1 CTC/7.5 ml) at baseline was associated with shorter 3-year disease-free survival (39% versus 70% for patients without CTC, P < 0.01, HR 2.80) and shorter 3-year overall survival (OS) (P < 0.01). In multivariate analysis, independent prognostic parameters for shorter survival were absence of hormonal receptors, no pCR and CTC detection at baseline. CEC level at baseline or variations during treatment had no prognostic value.



In this pooled analysis of two prospective trials in nonmetastatic IBC, detection rate of CTC was 39% with a strong and independent prognostic value for survival. Combination of pCR after neoadjuvant treatment with no CTC detection at baseline isolated a subgroup of IBC with excellent OS (94% 3-year OS), suggesting that CTC count could be part of IBC stratification in prospective trials.
Medical Oncology Department, Institut Curie, PSL Research University, Paris, France.
J-Y
JY
Pierga
Medical Oncology Department, Institut Curie, PSL Research University, Paris, France.
F-C
FC
Bidard
Biostatistics Department, Institut Paoli-Calmettes, Centre de Recherche en Cancérologie de Marseille, Marseille.
A
A
Autret
Medical Oncology Department, Centre Paul Strauss, Strasbourg.
T
T
Petit
Medical Oncology Department, Gustave Roussy INSERM Unit U981, Université Paris Sud, Villejuif.
F
F
Andre
Medical Oncology Department, Institut Claudius Regaud, IUCT, Toulouse.
F
F
Dalenc
Medical Oncology Department, Centre François Baclesse, Caen.
C
C
Levy
Medical Oncology Department, Centre Antoine Lacassagne, Nice.
J-M
JM
Ferrero
Medical Oncology Department, Institut du Cancer de Montpellier, Montpellier.
G
G
Romieu
Medical Oncology Department, Centre Oscar Lambret, Lille.
J
J
Bonneterre
Medical Oncology Department, Institut Curie, Saint Cloud.
F
F
Lerebours
Medical Oncology Department, Centre Léon Bérard, Lyon.
T
T
Bachelot
Medical Oncology Department, Centre Eugène Marquis, Rennes.
P
P
Kerbrat
Medical Oncology Department, Institut de Cancérologie de l'Ouest, ICO Angers Nantes.
M
M
Campone
Medical Oncology Department, Institut Jean Godinot, Reims.
J-C
JC
Eymard
Medical Oncology Department, Centre Jean Perrin, Clermont Ferrand.
M-A
MA
Mouret-Reynier
Medical Oncology Department, Hôpital Tenon, Assistance Publique des Hôpitaux de Paris, Université Pierre et Marie Curie, Paris.
J
J
Gligorov
Centre Armoricain de Radiothérapie d'Imagerie médicale et d'Oncologie, Plérin.
A-C
AC
Hardy-Bessard
Centre Catherine de Sienne, Nantes.
A
A
Lortholary
Medical Oncology Department, Institut de Cancérologie de l'Ouest, ICO Angers Nantes.
P
P
Soulie
Biostatistics Department, Institut Paoli-Calmettes, Centre de Recherche en Cancérologie de Marseille, Marseille.
J-M
JM
Boher
Medical Oncology Department, Institut Curie, PSL Research University, Paris, France.
C
C
Proudhon
Pathology Department, Institut Paoli-Calmettes, Centre de Recherche en Cancérologie de Marseille, Marseille.|Aix-Marseille Université, Marseille.
E
E
Charafe-Jaufret
R&D UNICANCER, UCBG, Paris.
J
J
Lemonnier
Aix-Marseille Université, Marseille.|Department of Medical Oncology, Centre de Recherche en Cancé rologie de Marseille, Institut Paoli-Calmettes, Marseille, France.
F
F
Bertucci
Aix-Marseille Université, Marseille.|Department of Medical Oncology, Centre de Recherche en Cancé rologie de Marseille, Institut Paoli-Calmettes, Marseille, France.
P
P
Viens
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D000077143:Docetaxel; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D058922:Inflammatory Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009360:Neoplastic Cells, Circulating / Q000187:drug effects* / Q000473:pathology*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D043823:Taxoids / Q000008:administration & dosage; D000068878:Trastuzumab / Q000008:administration & dosage; D055815:Young Adult
D000068258:Bevacizumab; D003520:Cyclophosphamide; D000077143:Docetaxel; D015251:Epirubicin; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; C508053:ERBB2 protein, human