Therapeutic intervention based on circulating tumor cell phenotype in metastatic breast cancer: concept of the DETECT study program.
OBJECTIVE
The aim of the ongoing DETECT study program is to evaluate therapeutic intervention based on phenotypes of circulating tumor cells (CTC) in patients with metastatic breast cancer (MBC). Currently (as of July 2015) more than half of the projected about 2000 patients with MBC have already been screened for CTC.


METHODS
Women with HER2-negative primary tumor and presence of CTC are recruited into different DETECT trials according to the HER2-phenotype of CTC. Patients with HER2-positive CTC are randomized to treatment with physicians' choice therapy (standard chemo- or endocrine therapy) with or without additional HER2-targeted therapy with lapatinib in the DETECT III trial. In DETECT IVa, postmenopausal patients with hormone-receptor positive primary cancer and HER2-negative CTC receive everolimus and standard endocrine therapy. For women with HER2-negative CTC and triple negative MBC or hormone-receptor positive tumor and indication for chemotherapy, a treatment with eribulin is offered (DETECT IVb). The clinical efficacy is investigated by CTC-Clearance and progression-free survival (PFS). The DETECT V/CHEVENDO trial extends the DETECT study program for women with HER2-positive and hormone-receptor positive MBC. The primary objective of this trial is to compare safety and quality of life (QoL) as assessed by the occurrence of adverse events in patients treated with dual (trastuzumab plus pertuzumab) HER2-targeted therapy plus either endocrine or chemotherapy. The translational research projects of the DETECT study program focus on further molecular characterization of CTC and evaluation of markers for their suitability to predict treatment response and to facilitate the development of more personalized treatment options.
Gynecology and Obstetrics, University Hospital Ulm, Prittwitzstraße 43, 89075, Ulm, Germany. Amelie.Schramm@uniklinik-ulm.de.
Amelie
A
Schramm
Gynecology and Obstetrics, University Hospital Ulm, Prittwitzstraße 43, 89075, Ulm, Germany.
Thomas W P
TW
Friedl
Gynecology and Obstetrics, University Hospital Ulm, Prittwitzstraße 43, 89075, Ulm, Germany.
Fabienne
F
Schochter
Gynecology and Obstetrics, University Hospital Ulm, Prittwitzstraße 43, 89075, Ulm, Germany.
Christoph
C
Scholz
Gynecology and Obstetrics, University Hospital Ulm, Prittwitzstraße 43, 89075, Ulm, Germany.
Nikolaus
N
de Gregorio
Gynecology and Obstetrics, University Hospital Ulm, Prittwitzstraße 43, 89075, Ulm, Germany.
Jens
J
Huober
Gynecology and Obstetrics, Hospital of Ludwig-Maximilians-University, Munich, Germany.
Brigitte
B
Rack
Gynecology and Obstetrics, Hospital of Ludwig-Maximilians-University, Munich, Germany.
Elisabeth
E
Trapp
Gynecology and Obstetrics, Hospital of Ludwig-Maximilians-University, Munich, Germany.
Marianna
M
Alunni-Fabbroni
Gynecology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Volkmar
V
Müller
National Center for Tumor Diseases and Department of Gynecology and Obstetrics, University Hospital Heidelberg, Heidelberg, Germany.
Andreas
A
Schneeweiss
Department of Tumor Biology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Klaus
K
Pantel
Gynecology and Obstetrics, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany.
Franziska
F
Meier-Stiegen
Gynecology and Obstetrics, University Hospital Tuebingen, Tuebingen, Germany.
Andreas
A
Hartkopf
Gynecology and Obstetrics, University Hospital Tuebingen, Tuebingen, Germany.
Florin-Andrei
FA
Taran
Gynecology and Obstetrics, University Hospital Tuebingen, Tuebingen, Germany.
Diethelm
D
Wallwiener
Gynecology and Obstetrics, University Hospital Ulm, Prittwitzstraße 43, 89075, Ulm, Germany.
Wolfgang
W
Janni
Gynecology and Obstetrics, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany.
Tanja
T
Fehm
D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000523:psychology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077341:Lapatinib; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods*; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D011788:Quality of Life; D011799:Quinazolines / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D000068878:Trastuzumab / Q000627:therapeutic use; D016896:Treatment Outcome
D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C485206:pertuzumab
Advanced breast cancer; Circulating tumor cells (CTC); DETECT study program; Endocrine responsiveness score; HER2-phenotype of CTC; Targeted therapy