Presence of apoptotic and nonapoptotic disseminated tumor cells reflects the response to neoadjuvant systemic therapy in breast cancer.
BACKGROUND
Neoadjuvant systemic therapy (NST) is an established strategy to reduce tumor size in breast cancer patients prior to breast-conserving therapy. The effect of NST on tumor cell dissemination in these patients is not known. The aim of this study was to investigate the incidence of disseminated tumor cells (DTC), including apoptotic DTC, in breast cancer patients after NST, and to investigate the correlation of DTC status with therapy response.


METHODS
Bone marrow aspiration was performed in 157 patients after NST. DTC were detected by immunocytochemistry using the A45-B/B3 anticytokeratin antibody. To detect apoptotic DTC the antibody M30 (Roche Diagnostics, Germany) was used, which detects a neo-epitope expressed only after caspase cleavage of cytokeratin 18 during early apoptosis.


RESULTS
The incidence of DTC in breast cancer patients was 53% after completion of NST. Tumor dissemination was observed more frequently in patients with no change/progressive disease (69%) than in patients with partial remission or complete remission of the primary tumor (46%) (P < 0.05). Ten out of 24 patients with complete remission, however, were still bone marrow positive. Apoptotic DTC were present in 36 of 157 (23%) breast cancer patients. Apoptotic cells only were detected in 14% of the patients with partial remission or complete remission, but were detected in just 5% of the patients with stable disease. Apoptotic DTC were detectable in none of the patients with tumor progression.


CONCLUSIONS
The pathological therapy response in breast cancer patients is reflected by the presence of apoptotic DTC. Patients with complete remission, however, may still have nonapoptotic DTC. These patients may also benefit from secondary adjuvant therapy.
Fehm
Tanja
T
Department of Obstetrics and Gynecology, University of Tuebingen, Calwerstrasse 7, D-72076 Tuebingen, Germany. Tanja.fehm@t-online.de
Becker
Sven
S
Becker-Pergola
Graziella
G
Sotlar
Karl
K
Gebauer
Gerhard
G
Dürr-Störzer
Silke
S
Neubauer
Hans
H
Wallwiener
Diethelm
D
Solomayer
Erich-Franz
EF
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D019046:Bone Marrow Neoplasms / Q000473:pathology* / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D020360:Neoadjuvant Therapy; D009360:Neoplastic Cells, Circulating / Q000473:pathology*
D000970:Antineoplastic Agents