Neoadjuvant Chemotherapy of Patients with Early Breast Cancer Is Associated with Increased Detection of Disseminated Tumor Cells in the Bone Marrow

Preclinical data suggest that neoadjuvant chemotherapy (NAT) may promote micrometastatic spread. We aimed to compare the detection rate and prognostic relevance of disseminated tumor cells (DTCs) from the bone marrow (BM) of patients with early-stage breast cancer (EBC) after NAT with that of therap...

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Published in:Cancers 2022-01, Vol.14 (3), p.635
Main Authors: Volmer, Léa, Koch, André, Matovina, Sabine, Dannehl, Dominik, Weiss, Martin, Welker, Ganna, Hahn, Markus, Engler, Tobias, Wallwiener, Markus, Walter, Christina Barbara, Oberlechner, Ernst, Brucker, Sara Yvonne, Pantel, Klaus, Hartkopf, Andreas
Format: Article
Language:English
Subjects:
Bone cancer
Bone marrow
Bone tumors
Breast cancer
Cancer therapies
Chemotherapy
Estrogens
Leukocytes (mononuclear)
Lymphatic system
Medical prognosis
Minimal residual disease
Multivariate analysis
Patients
Surgery
Survival analysis
Tumor cells
Tumors
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Summary:Preclinical data suggest that neoadjuvant chemotherapy (NAT) may promote micrometastatic spread. We aimed to compare the detection rate and prognostic relevance of disseminated tumor cells (DTCs) from the bone marrow (BM) of patients with early-stage breast cancer (EBC) after NAT with that of therapy-naive EBC patients. DTCs were identified from BM samples, collected during primary surgery. Patients who received NAT were compared to patients who received chemotherapy after surgery. In total, 809 patients were analyzed. After NAT, 45.4% of patients were DTC-positive as compared to 19.9% of patients in the adjuvant chemotherapy group ( < 0.001). When sampled in patients who had undergone NAT, the detection of DTCs in the BM was significantly increased (OR: 3.1; 95% confidence interval (CI): 2.1-4.4; < 0.001). After NAT, DTC-positive patients with ≥2 DTCs per 1.5 × 10 mononuclear cells in their BM had an impaired disease-free survival (HR: 4.8, 95% CI: 0.9-26.6; = 0.050) and overall survival (HR: 4.2; 95% CI: 1.4-12.7; = 0.005). The higher rate of DTC-positive patients after NAT as compared to a treatment-naive comparable control cohort suggests that NAT supports tumor cell dissemination into the bone marrow. DTC positivity in BM predicted relapse in various distant organs, implying that tumor cell dissemination was not restricted to the bone marrow.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers14030635