Detection and HER2 expression of circulating tumor cells: prospective monitoring in breast cancer patients treated in the neoadjuvant GeparQuattro trial.
OBJECTIVE
This study was aimed at detecting and characterizing circulating tumor cells (CTC) before and after neoadjuvant therapy (NT) in the peripheral blood of patients with breast cancer.


METHODS
The clinical trial GeparQuattro incorporated NT approaches (epirubicin/cyclophosphamide prior to randomization to docetaxel alone, docetaxel in combination with capecitabine, or docetaxel followed by capecitabine) and additional trastuzumab treatment for patients with HER2-positive tumors. We used the Food and Drug Administration-approved CellSearch system for CTC detection and evaluation of HER2 expression and developed HER2 immunoscoring for CTC.


RESULTS
We detected > or =1 CTC/7.5 mL in 46 of 213 patients (21.6%) before NT and in 22 of 207 patients (10.6%) after NT (P = 0.002). Twenty (15.0%) initially CTC-positive cases were CTC-negative after NT, whereas 11 (8.3%) cases were CTC-positive after NT, although no CTC could be found before NT. CTC detection did not correlate with primary tumor characteristics. Furthermore, there was no association between tumor response to NT and CTC detection. HER2-overexpressing CTC were observed in 14 of 58 CTC-positive patients (24.1%), including 8 patients with HER2-negative primary tumors and 3 patients after trastuzumab treatment. CTC scored HER2-negative or weakly HER2-positive before or after NT were present in 11 of 21 patients with HER2-positive primary tumors. HER2 overexpression on CTC was restricted to ductal carcinomas and associated with high tumor stage (P = 0.002).


CONCLUSIONS
CTC number was low in patients with primary breast cancer. The decrease in CTC incidence during treatment was not correlated with standard clinical characteristics and primary tumor response. Information on the HER2 status of CTC might be helpful for stratification and monitoring of HER2-directed therapies.
Riethdorf
Sabine
S
Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Müller
Volkmar
V
Zhang
Liling
L
Rau
Thomas
T
Loibl
Sibylle
S
Komor
Martina
M
Roller
Marc
M
Huober
Jens
J
Fehm
Tanja
T
Schrader
Iris
I
Hilfrich
Jörn
J
Holms
Frank
F
Tesch
Hans
H
Eidtmann
Holger
H
Untch
Michael
M
von Minckwitz
Gunter
G
Pantel
Klaus
K
D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D000069287:Capecitabine; D045744:Cell Line, Tumor; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage; D005455:Fluorescent Antibody Technique; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000097:blood; D043823:Taxoids / Q000008:administration & dosage; D013997:Time Factors; D000068878:Trastuzumab; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000069287:Capecitabine; D003520:Cyclophosphamide; D003841:Deoxycytidine; D000077143:Docetaxel; D015251:Epirubicin; D005472:Fluorouracil; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab