Lobular phenotype related to occult-metastatic spread in axillary sentinel node and/or bone marrow in breast carcinoma
ABSTRACT To determine whether any histological trait was associated with regional and/or systemic spread of occult tumour cells (OTCs) in small size invasive breast cancer, we compared tumour characteristics, axillary sentinel lymph node (SN) and bone marrow (BM) status in a series of 287 pT1T2 cases. Surgery was the first step of treatment, associated with SN procedure and with BM aspiration for the detection of OTC. SN was histologically classified as negative, metastatic (>2mm), micro-metastatic (>0.2mm and 2mm) or involved by OTC detected by immunohistochemistry (Ni+, 0.2mm). BM specimens were analysed after immunocytochemistry and classified as negative or positive with atypical cytokeratin-positive OTC. Metastasis and micro-metastasis in the SN were correlated with size, grade and vascular invasion. In contrast, presence of OTC in both SN and BM was independent of these parameters but positively associated with lobular type. This correlation was also observed for BM status, which was similarly independent of the tumour characteristics. No association was found between SN status and BM status. Our data indicate that, in the course of breast cancer, OTC spreading is frequent and could be an early event, related to lobular histological type but independent of classical histoprognostic parameters, and that the loco-regional metastatic spread of OTC is not a prerequisite for systemic involvement.
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ABSTRACT: Due to its non-invasiveness, high temporal resolution and lower cost, fluorescence imaging is an interesting alternative to the current method (blue dye and radiocolloid) of sentinel lymph node (SLN) mapping in breast cancer. Near-infrared (NIR) emitting cadmium-based Quantum Dots (QDs) could be used for this purpose; however, their wide application is limited because of the toxicity of heavy metals composing the core. Our recent work demonstrated that indium-based QDs exhibit a weak acute local toxicity in vivo compared to their cadmium-based counterparts. In the present study we confirmed the weak toxicity of CuInS(2)/ZnS QDs in different in vitro models. Further in vivo studies in healthy mice showed that In-based QDs could be visualised in SLN in a few minutes after administration with a progressive increase in fluorescence until 8 h. The quantity of indium was assessed in selected organs and tissues by inductively coupled plasma - mass spectroscopy (ICP-MS) as a function of post-injection time. QD levels decrease rapidly at the injection point in the first hours after administration with a parallel increase in the lymph nodes and to a lesser extent in the liver and spleen. In addition, we observed that 3.5% of the injected indium dose was excreted in faeces in the first 4 days, with only trace quantities in the urine. Metastatic spread to the lymph nodes may hamper its visualisation. Therefore, we further performed non-invasive fluorescence measurement of QDs in SLN in tumour-bearing mice. Metastatic status was assessed by immunohistology and molecular techniques and revealed the utmost metastatic invasion of 36% of SLN. Fluorescence signal was the same irrespective of SLN status. Thus, near-infrared emitting cadmium-free QDs could be an excellent SLN tracer.PLoS ONE 08/2012; 7(8):e44433. DOI:10.1371/journal.pone.0044433 · 3.53 Impact Factor
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ABSTRACT: Background:The enumeration of circulating tumour cells (CTCs) with the EpCAM-based CellSearch system has prognostic significance in patients with metastatic breast cancer (MBC). The aim of this study was to explore potential differences in the detection and prognostic significance of CTCs in MBC according to immunohistochemical subtypes of breast cancer.Methods:CellSearch CTC counts were obtained from 154 MBC patients before first-line systemic treatment between November 2007 and August 2012. Patients were categorised in five subgroups according to immunohistochemical surrogate definitions of intrinsic subtypes in breast cancer based on hormone receptor status, HER2/neu status and histological grade. Differences in progression-free (PFS) and overall survival (OS) were assessed relative to the cut-off value of 5 CTCs per 7.5 ml blood.Results:No significant differences were observed in the absolute CTC counts (P=0.120) or in CTC positivity rates according to 1 and 5 CTCs per 7.5 ml blood detection thresholds (P=0.165 and P=0.651, respectively) between immunohistochemical subtypes. However, very high CTC counts, defined as 80 CTCs per 7.5 ml, were observed more frequently in patients with Luminal A and triple negative (TN) breast cancer (P=0.024). In the total study population, the presence of 5 CTCs was the single most significant prognostic factor for both PFS and OS in multivariate analysis (P<0.001). A more limited prognostic impact, not reaching statistical significance, was observed in patients with HER2-positive disease as opposed to patients with Luminal A, Luminal B-HER2-negative and TN disease.Conclusion:The detection of EpCAM+CTCs was not clearly associated with any of the immunohistochemical subtypes of breast cancer in patients with MBC before first-line treatment. Potentially clinically relevant differences were however observed at very high CTC counts. Furthermore, our data suggest a lower prognostic significance of CTC evaluation in HER2-positive patients with MBC.British Journal of Cancer advance online publication, 24 December 2013; doi:10.1038/bjc.2013.743 www.bjcancer.com.British Journal of Cancer 12/2013; 110(2). DOI:10.1038/bjc.2013.743 · 4.82 Impact Factor
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ABSTRACT: In the past decade, sentinel lymph node biopsy (SLNB) has become standard for patients with early-stage clinically node-negative breast carcinoma (BC). Despite high overall surgical identification success rates with introduction of the dual-tracer techniques (dye and radiolabeled probe), false-negative rates remained unchanged in most recent meta-analyses. We analyzed cases with false-negative SLN biopsy results over a 12-year period in a single institution to evaluate their clinicopathologic characteristics. Sixty-three false-negative cases (3.1%) were found in 2043 successful SLN mapping procedures, all of which were followed by varying amounts of additional axillary sampling. There was a higher proportion of invasive lobular carcinomas (ILCs; 23 cases [37%]) when compared with this lesion's overall reported frequency (5%-15%). The majority of invasive ductal carcinoma (IDC) cases (31 of 40) were poorly differentiated. In 80% of the ductal-type cases, 1 or more nonsentinel nodes (NSLNs) were completely or partially replaced by tumor, as opposed to less than half of such cases of the lobular type. Twenty-two cases had multiple positive NSLN metastases, which were significantly associated with larger tumor size (≥ 1.0 cm) and tumor replacement of NSLNs. Eighty-two percent of the cases with known hormone receptor status were positive for estrogen or progesterone receptors, or both. False-negative SLN biopsy results were more often associated with a primary BC characterized by a lobular or poorly differentiated ductal histologic type or partial to complete replacement of NSLNs with tumor, or both.Clinical Breast Cancer 01/2014; DOI:10.1016/j.clbc.2013.12.009 · 2.63 Impact Factor