Prognostic value of hematogenous dissemination and biological profile of the tumor in early breast cancer patients: A prospective observational study

Abstract

BackgroundThe aim of this study was to investigate the incidence and prognostic value of disseminated tumor cells in bone marrow of breast carcinoma patients with early disease, and to analyze this finding in relation to lymph node involvement, determined by sentinel lymph node (SLN) biopsy analysis, and to prognostic factors of interest.Methods104 patients with operable (T < 3 cm) breast cancer and clinically- and sonographically-negative axillary lymph nodes were scheduled for SLN biopsy. Bone marrow aspirates were collected before the start of surgery from both iliac crests, and mononuclear cell layers were separated by density centrifugation (Lymphoprep). Slide preparations were then examined for the presence of disseminated tumor cells by immunocytochemistry with anti-cytokeratin antibodies (A45-B/B3). Lymphoscintigraphy was performed 2 hours after intratumor administration of 2 mCi (74 MBq) of 99mTc colloidal albumin. The SLN was evaluated for the presence of tumor cells by hematoxylin-eosin staining and, when negative, by immunocytochemistry using anti-cytokeratin antibody (CAM 5.2). Survival analyses and comparative analyses were performed on the results of bone marrow determinations, SLN biopsy, and known prognostic factors, including breast cancer subtypes according to the simplified classification based on ER, PR and HER2.ResultsLymph node and hematogenous dissemination occur in one-third of patients with early-stage breast cancer, although not necessarily simultaneously. In our study, disseminated tumor cells were identified in 22% of bone marrow aspirates, whereas 28% of patients had axillary lymph node involvement. Simultaneous lymph node and bone marrow involvement was found in only 5 patients (nonsignificant). In the survival study (60 months), a higher, although nonsignificant rate of disease-related events (13%) was seen in patients with disseminated tumor cells in bone marrow, and a significant association of events was documented with the known, more aggressive tumor subtypes: triple negative receptor status (21%) and positive ERBB2 status (29%).ConclusionsTumor cell detection in bone marrow can be considered a valid prognostic parameter in patients with early disease. However, the classic prognostic factors remain highly relevant, and the newer breast cancer subtypes are also useful for this purpose.

Analysis of and prognostic information from disseminated tumour cells in bone marrow in primary breast cancer: a prospective observational study

“…Aspects to consider when estimating the results of these early reports are the heterogeneity of the patients included and different methods and techniques used to determine bone marrow dissemination. However, more recent studies performed with standardised methods of detection also propose a prognostic value of DTCs in bone marrow [ 22 - 24 ]. Molloy et al found clinical significance of DTCs in bone marrow in terms of BCSS (HR, 2.1; p = 0.003), but not in metastasis-free survival (HR, 1.5; p = 0.127) [ 23 ].…”

“…They concluded that bone marrow aspiration was not recommended in routine clinical practice for patients with early breast cancer without an improved technique for isolation and detection of occult tumour cells in bone marrow [ 22 ]. Solá et al found a higher frequency of DTCs in a subgroup of patients who experienced breast cancer-related events (13%), but the results did not reach statistical significance because of low power with few events [ 24 ]. Future studies will show whether there is a predictive value in the choice of chemotherapy regarding repeated sampling of DTCs during progression of the disease.…”

Les étapes précoces du processus métastatique

“…Par exemple, dans la majorité des cancers du sein, la dissémination des cellules tumorales semble avoir lieu beaucoup plus tôt que ne le pré-voit le modèle linéaire ( Figure 2B). Il est maintenant établi que des cellules cancéreuses circulent dans le sang ou sont présentes dans la moelle osseuse d'environ un tiers des patientes atteintes d'un cancer du sein à un stade précoce [4,[5][6][7]. Dans de nombreux cas, des cellules cancéreuses métastatiques seraient même présentes avant que la tumeur primitive ne soit détectée cliniquement.…”

“…Au cours de la gastrulation, des cellules d'origine ectodermique migrent vers la ligne primitive, puis perdent leur caractère épithélial conduisant à l'acquisition de cellules mésen-chymateuses qui donnent naissance au mésoderme et à l'endoderme [17]. [5]. Cela indique que, dans la plupart des cas, l'organisme est capable de contrôler la prolifération des cellules cancéreuses disséminées.…”