Prognostic Implications of Isolated Tumor Cells and Micrometastases in Sentinel Nodes of Patients with Invasive Breast Cancer: 10-Year Analysis of Patients Enrolled in the Prospective East Carolina University/Anne Arundel Medical Center Sentinel Node Multicenter Study
Sentinel lymph node biopsy (SLNB) is a more sensitive and accurate nodal staging procedure than axillary lymph node dissection (ALND). Because of increased pathologic evaluation in the sentinel node era, more nodal micrometastases (MIC) (> 0.2 mm to 2 mm) and isolated tumor cells (ITC; < or = 0.2 mm) have been identified. We present the 10-year analysis of our prospective SLN study, focusing on regional axillary node status and distant metastases in patients with nodal ITC and MIC.
From 1996 to 2005, breast cancer patients were enrolled in an Institutional Review Board-approved, multicenter study. SLNs were examined at multiple levels by hematoxylin and eosin; most (85%) hematoxylin and eosin-negative SLNs were also examined by cytokeratin immunohistochemistry. Data from 1,259 patients with invasive breast cancer and in whom an SLN was found were reviewed for this analysis.
Of the 1,259 patients, 893 (71%) had negative SLNs, 25 (2%) had ITCs, 57 (5%) had MIC, and 284 (23%) had positive SLNs. None of the 13 patients with ITCs who underwent an ALND had additional positive nodes, compared with 27% (11 of 41) of patients with MIC. At a mean followup of 4.9 years, the distant recurrence rates for SLN-negative, ITC, MIC, and SLN-positive groups were 6%, 8%, 14%, and 21%, respectively. The presence of MIC in the SLN was associated with a significantly shorter disease-free interval than was SLN negativity (p < 0.02 by Cox regression model).
This prospective breast cancer study found that sentinel node MIC, but not ITCs, were associated with additional positive nodes and with distant recurrence. These data suggest that ALND may be unnecessary in patients with ITCs. But ALND and more aggressive adjuvant therapy should be considered in patients with SLN micrometastases.
Available from: PubMed Central
- "It is difficult for the pathologist to find all possible foci of microinvasion in very extensive DCIS. The multifocality of microinvasive disease is in correlation with positive sentinel nodes [6,11]. "
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Microinvasive ductal carcinoma in situ of the breast is a rare entity defined as ductal carcinoma in situ with invasive foci measuring no more than 1 mm. In general, the outcome is excellent, similar to ductal carcinoma in situ. We report a patient with breast ductal carcinoma in situ with microinvasion who died eight months after diagnosis due to progression of the disease – liver metastases. This is the first report in the literature of such an aggressive course.
A 47-year-old Caucasian woman presented with mammographic-detected suspicious microcalcinations in an area of 8.6 x 6 cm. A radical mastectomy with a sentinel lymph node biopsy and immediate breast reconstruction with implant was performed. A histopathological report showed a massive high grade ductal carcinoma in situ, of the solid and comedo type. In one quadrant, some foci of microinvasions of less than 1 mm were present. Tumour margins were free. Isolated tumour cells were found in the sentinel lymph node. Hormone receptors were negative and human epidermal growth factor receptor-2 status was not performed. The patient received no adjuvant systemic therapy. Eight months after the surgery, she died from hepatic failure without known breast cancer progression before. An autopsy revealed diffuse liver metastases with human epidermal growth factor receptor 2-positive, hormone receptor negative breast cancer. Dissemination to other organs was not proven.
Our patient is a rare case of ductal carcinoma in situ with microinvasion that developed distant metastases very early. In case of multiple foci of microinvasion, besides radical local treatment we suggest considering adjuvant systemic treatment based on biological characteristics since tumour size alone does not predict the prognosis well.
Available from: Earle Holmes
- "The dimension of tumor involvement in positive LNs has been distinguished in stages N0 and N1 as isolated tumor cells, tumor clusters, and micrometastasis by AJCC LN staging system . Survival analyses of the breast cancer patients with isolated tumor cells and micrometastasis in the sentinel lymph nodes showed controversial results      . There is no further distinction of tumor dimension above 2 mm in the LNs, whereas only the metLN is taken into account. "
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ABSTRACT: The number of positive axillary lymph nodes (LNs) is the only node-related factor for prognostic evaluation of breast cancer recognized by AJCC (TNM staging). However, N staging may not completely reflect LN tumor involvement due to the erroneous count of LNs in the presence of matted LNs and different tumor volume in LNs. Additionally, the positive/total LN ratio (LNR) has been shown to outperform N staging in survival prediction. In our study, to better quantify the tumor involvement of axillary LNs, we measured the cross-sectional cancer area (CSCA) of the positive LNs in 292 breast cancer patients diagnosed between 1998 and 2000 in our institution and compared its prognostic value to that of number of positive LNs (metLN)/N stage and LNR. Statistical analyses of these three LN-related factors were performed by Kaplan-Meier method and multivariate Cox's regression model. Patients were divided into three groups based on the different LN CSCA (<50, 50-500, and >500 mm(2)), or LNR (<0.1, 0.1-0.65, and >0.65), or N stage (N1-N3). Multivariate analysis demonstrated LNR was the most significant LN-related survival predictor with hazard ratio (HR) 25.0 (P = 0.001), compared to the metLN (HR 0.09, P = 0.052) and CSCA (HR 2.24, P = 0.323).
Available from: Ian S Fentiman
- "The largest study; however, found a significantly worse disease-free survival for women with micrometastases who did not undergo cALND. . "
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ABSTRACT: Sentinel lymph node biopsy (SLNB) is a safe and accurate minimally invasive method for detecting axillary lymph node (ALN) involvement in the clinically negative axilla thereby reducing morbidity in patients who avoid unnecessary axillary lymph node dissection (ALND). Although current guidelines recommend completion ALND when macro- and micrometastatic diseases are identified by SLNB, the benefit of this surgical intervention is under debate. Additionally, the management of the axilla in the presence of isolated tumour cells (ITCs) in SLNB is questioned. Particularly controversial is the prognostic significance of minimal SLNB metastasis in relation to local recurrence and overall survival. Preliminary results of the recently published Z0011 trial suggest similar outcomes after SNB or ALND when the SN is positive, but this finding has to be interpreted with caution.
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