Time to metastatic relapse and breast cancer cells dissemination in bone marrow at metastatic relapse.
Breast cancer dissemination can be monitored in patients by detecting circulating and/or disseminated tumor cells. However, bone marrow disseminated tumor cells (BM DTC) may undergo a dormancy during several years before growing (or not) into clinically detectable metastases. We therefore hypothesized that breast cancers which have formed BM DTC in the course of their metastatic growth might exhibit a longer interval before metastatic relapse. We examined the association of DTC detection (cytokeratin 8, 18 or 19 positive epithelial cells with cancerous morphological features), at metastatic relapse, with the metastasis-free interval in breast cancer patients. In the 110 metastatic patients studied, 42% (n = 64/110) were classified as BM DTC-negative. These patients had a significantly shorter metastasis-free interval than BM DTC-positive patients (P = 0.02). In multivariate logistic regression analysis, the metastasis-free interval was an independent predictor of DTC detection (P = 0.02), together with bone metastasis (P = 0.0003) and low tumor grade (grade I or II, P = 0.05). We finally suggest that a faster metastatic process might skip in some patients the BM DTC-associated dormancy step. Dissemination of DTC in other host organ and/or epithelial-mesenchymal transition from cytokeratin-positive to cytokeratin-negative DTC may explain this observation.
Bidard
François-Clément
FC
Department of Medical Oncology, Institut Curie, 26 Rue d'Ulm, 75005, Paris, France. francois-clement.bidard@curie.fr
Vincent-Salomon
Anne
A
Sigal-Zafrani
Brigitte
B
Rodrigues
Manuel
M
Diéras
Véronique
V
Mignot
Laurent
L
Sastre-Garau
Xavier
X
Poupon
Marie-France
MF
Pierga
Jean-Yves
JY
D001853:Bone Marrow / Q000473:pathology; D001859:Bone Neoplasms / Q000378:metabolism / Q000556:secondary*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D053538:Keratin-18 / Q000378:metabolism; D053539:Keratin-19 / Q000378:metabolism; D053533:Keratin-8 / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary*; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary*; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology*; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D013997:Time Factors
D053538:Keratin-18; D053539:Keratin-19; D053533:Keratin-8