Detection Of Breast Cancer Metastasis Research Articles

A study of the assessment of axillary lymph nodes before surgery for breast cancer using multidetector-row computed tomography

Sentinel lymph node biopsy (SLNB) is widely used in the detection of breast cancer metastasis, and a retrospective study was conducted to determine whether the preoperative assessment of axillary lymph node metastasis using multidetector-row computed tomography (MDCT) images would contribute to the selection of patients who require SLNB. Seventy of the 164 patients who underwent surgery of the breast during the period of April 2006 to December 2008 were selected as subjects who: (1) did not undergo preoperative chemotherapy; (2) had undergone MDCT before the surgery; (3) had undergone either SLNB or axillary lymph node removal during the operation; and (4) whose T factor was pathologically T2 or less. The diameter and shape of the largest lymph node that was identified on an MDCT image of the axilla on the affected side were measured and compared with permanent pathological specimens. Size: The group with lymph node metastasis included 21 subjects with an average diameter of the largest lymph node of 10.3 mm (range, 6-23 mm), and the nonmetastasis group included 49 subjects with that of 7.1 mm (5-13 mm). Shape: Round lymph nodes that internally contained no fat concentration in 24 subjects, and cuneate or round lymph nodes that internally contained a fat concentration in 46 subjects. The observable lymph nodes that were round had a diameter of at least 10 mm, and internally contained no fat concentration (A) were regarded as positive, whereas the cuneate or round lymph nodes that measured less than 8 mm in diameter and internally contained fat concentration (B) were regarded as negative, and both positive predictive value and negative predictive value was 100%. Axilla removal was performed from the beginning in the case of (A) by assessing the size and shape for the presence or absence of axillary lymph node metastasis before surgery using MDCT.

CSLEX (Sialyl Lewis X) is a Useful Tumor Marker for Monitoring of Breast Cancer Patients

CSLEX is a type II carbohydrate antigen that interacts with the CSLEX-1 monoclonal antibody. CSLEX in combination with carbohydrate antigen 15-3 may be more useful than Carcinoembryonic Antigen with carbohydrate antigen 15-3 as tumor markers for monitoring of breast cancer. The serum levels of tumor markers, including CSLEX, were measured in 480 consecutive breast cancer patients with or without metastasis who visited the outpatient clinic of the Division of Breast and Endocrine Surgery, Shinshu University Hospital, between April 2007 and September 2007. Serum levels of each of the tumor markers correlated significantly with the status of metastasis (P < 0.01). Combinations of Carcinoembryonic Antigen and carbohydrate antigen 15-3, Carcinoembryonic Antigen and Nation Cancer Center-Stomach-439, Carcinoembryonic Antigen and CSLEX, carbohydrate antigen 15-3 and Nation Cancer Center-Stomach-439, and carbohydrate antigen 15-3 and CSLEX levels also correlated significantly with the status of metastasis (P < 0.01). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were almost the same for CSLEX and Nation Cancer Center-Stomach-439, which are both type II carbohydrate antigens. The cutoff indexes of serum CSLEX and Nation Cancer Center-Stomach-439 for detection of breast cancer metastasis were 38.8 ± 52.7-fold and 22.1 ± 27.8-fold, respectively (P = 0.16). These data suggest that the diagnostic values of CSLEX and Nation Cancer Center-Stomach-439 are similar in single or combined use. However, the cutoff index of serum CSLEX tended to be higher than that of Nation Cancer Center-Stomach-439, which may make CSLEX more useful for detection of breast cancer metastasis.

Abstract LB-216: CSLEX (sialyl LewisX) is an important and useful tumor marker in monitoring breast cancer patients

Abstract Background: CSLEX-1 is one of the monoclonal antibodies for which the structure of the antigen is known. This antigen is called CSLEX (Sialyl Le X). It has been reported that CSLEX may be more useful than CEA in combination with CA15-3 in monitoring breast cancer patients. Methods: We measured and evaluated the serum levels of some tumor markers, including CSLEX, in a total of 482 breast cancer patients with or without metastasis who consecutively visited the outpatient clinic of the Division of Breast and Endocrine Surgery, Shinshu University Hospital, between April 2007 and September 2007. Results: All serum levels of tumor markers in a single measurement correlated significantly with the status of metastasis (P &amp;lt; 0.01). All combinations of combined measurements, such as CEA and CA15-3, CEA and NCC-ST439, CEA and CSLEX, CA15-3 and NCC-ST439, and CA15-3 and CSLEX, also correlated significantly with the status of metastasis (P &amp;lt; 0.01). The sensitivity, specificity, positive-predictive value, negative-predictive value and accuracy were almost the same between CSLEX and NCC-ST439, which belongs to the type II carbohydrate antigens. The cut-off values of serum CSLEX and NCC-ST439 were 38.8 ± 52.7 U/ml and 22.1 ± 27.8 U/ml, respectively (P = 0.16). Conclusions: These data support there are no differences between CSLEX and NCC-ST439 as diagnostic parameters in single or combined measurements. The cut-off value of serum CSLEX tended to be higher compared with that of NCC-ST439.Patient characteristics Without MetastasisWith MetastasisP-valueNumber363119 Mean Age ± SD (years)56.5 ± 11.758.9 ± 12.60.06CEA2.5 ± 6.311.9 ±34.50.008CA15-311.9 ± 11.166.4 ± 162.50.001BCA22561.0 ±51.5139.4 ± 228.60.001NCCST-4392.0 ± 2.234.2 ± 108.20.003CSLEX3.4 ± 3.765.6 ± 223.10.005Diagnostic parameters for the detection of breast cancer metastasis using tumor markers (%) SensitivitySpecificityPPVNPVAccuracySingle measurement CEA3095688179CA15-33498828282BCA2251698707878NCC-ST4392497727979CSLEX2397697978Combined measurement CEAandCA15-34893698482CEA and NCC-ST4394392648380CEA and CSLEX4392658380CA15-3 and NCC-ST4394595758483CA15-3 and CSLEX4495738482 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-216.

Detection of breast cancer metastasis in sentinel lymph nodes using intra-operative real time GeneSearch™ BLN Assay in the operating room: results of the Cardiff study

Intra-operative assessment is not routinely performed in the UK due to poor sensitivity of available methods and overburdened pathology resources. We conducted a prospective clinical feasibility study of the GeneSearch Breast Lymph Node (BLN) Assay (Veridex, LLC, Warren, NJ) to confirm its potential usefulness within the UK healthcare system. In the assay 50% of the lymph node was processed to detect the presence of cytokeratin-19 and mammaglobin mRNA. The assay was calibrated to detect metastases >0.2 mm. Assay results were compared to H&E performed on each face of approximately 2 mm alternating node slabs and 3 additional sections cut at approximately 150 microm interval from each face of the node slab. 124 sentinel lymph nodes were removed from 82 breast cancer patients. The assay correctly identified all 6 patients with sentinel node macrometastases (>2.0 mm), and 2 of 3 patients with sentinel node micrometastases (0.2-2.0 mm). Sentinel lymph nodes in 4 patients were assay positive but histology negative. Two of these four patients had isolated tumor cells seen by histology. The overall concordance with histology was 93.9% (77/82), with sensitivity of 88.9% (8/9, 95% CI 56.5-98%), specificity of 94.6% (69/73, 95% CI 86.7-97.8%), positive predictive value of 66.7% (8/12, 95% CI 39.1-86.2%) and negative predictive value of 98.6% (69/70, 95% CI 92.3-99.7%). The assay was performed in a median time of 32 min (range 26-69 min). Intra-operative assessment of sentinel lymph node can be performed rapidly and accurately using the GeneSearch BLN Assay.

2–26 Identification and Characterization of Optimal Gene Expression Markers for Detection of Breast Cancer Metastasis

2–26 Identification and Characterization of Optimal Gene Expression Markers for Detection of Breast Cancer Metastasis

An evaluation of molecular markers for improved detection of breast cancer metastases in sentinel nodes

Background and objectives: In patients with breast cancer (BC), the sentinel node (SN) is the first node in the axillary basin that receives the primary lymphatic flow and can be...

Multimarker RT–PCR assay for the detection of minimal residual disease in sentinel lymph nodes of breast cancer patients

The presence of metastases in lymph nodes is the most powerful prognostic factor in breast cancer patients. Routine histological examination of lymph nodes has limited sensitivity for the detection of breast cancer metastases. The aim of the present study was to develop a multimarker reverse transcriptase–polymerase chain reaction (RT—PCR) assay for the detection of minimal residual disease in sentinel nodes of breast cancer patients. RNA was extracted from 30 sentinel lymph nodes (SLN) obtained from 28 patients, three primary breast cancers (positive controls), three lymph nodes from patients with benign diseases, and peripheral blood lymphocytes of 10 healthy volunteers (negative controls). RT–PCR was performed using the following markers; cytokeratin (CK)-19, NY-BR-1 and mammaglobin B. RT–PCR results were compared to enhanced histopathologic examination and immunohistochemistry (IHC). All three positive controls showed strong PCR amplification for all three markers. None of the 13 negative controls was amplified by any of the three markers. Among the 30 SLN analysed, breast cancer metastases were detected in six SLNs by routine histology, in eight by IHC and in 15 by RT–PCR. We conclude that a multimarker RT–PCR assay probing for NY-BR-1, mammaglobin-B, and CK-19 is more sensitive compared to enhanced pathologic examination. This method may prove to be of value in breast cancer staging and prognosis evaluation.

Identification and Characterization of Optimal Gene Expression Markers for Detection of Breast Cancer Metastasis

Sentinel lymph node (SLN) status is highly predictive of overall axillary lymph node involvement in breast cancer. Historically, SLN-positive patients have undergone axillary lymph node dissection in a second surgery. Intraoperative SLN analysis could reduce the cost and complications of a second surgery; however, existing histopathological methods lack standardization and exhibit poor sensitivity. Rapid molecular methods may lead to improved intraoperative diagnosis of SLN metastasis. In this study, we used a genome-wide gene expression analysis of breast and other tissues to identify seven putative markers for detecting breast cancer metastasis. We assessed the utility of these markers for identifying clinically actionable metastases in lymph nodes through reverse transcriptase-polymerase chain reaction analysis of SLNs from 254 breast cancer patients. Polymerase chain reaction signals were compared to pathology on a per-patient basis. The optimal two-gene combination, mammaglobin and cytokeratin 19, detected clinically actionable metastasis in breast SLNs with 90% sensitivity and 94% specificity. Application of stringent criteria for identifying presumptive hematoxylin- and eosin-positive samples increased sensitivity and specificity to 91 and 97%, respectively. This study represents the first comprehensive demonstration of the utility of gene expression markers for detecting clinically actionable breast metastases. An intraoperative molecular assay using these markers has the potential to significantly reduce second surgeries for patients undergoing SLN dissection.

Detection of micrometastases in lymph nodes from patients with breast cancer.

Sentinel node biopsy affords the opportunity of focused examination of lymph nodes, including the use of the reverse transcriptase-polymerase chain reaction (RT-PCR). The mammaglobin gene is expressed by breast cancers but has not been detected in histologically normal lymph nodes. This study compared mammaglobin RT-PCR with routine histology in the sentinel and non-sentinel nodes of patients with breast cancer. Patients with breast cancer underwent tumour excision, sentinel node biopsy and axillary dissection. All nodes were bisected and half of each node was sent for routine histological examination. The other half underwent RNA extraction and mammaglobin RT-PCR. Sentinel node biopsy was successful in 50 (96 per cent) of 52 patients. Mammaglobin expression was detected in nine (8 per cent) of 119 histologically negative sentinel nodes (Clopper-Pearson 95 per cent confidence interval (c.i.) 4 to 14 per cent) and in 13 (5 per cent) of 247 histologically negative non-sentinel nodes (95 per cent c.i. 3 to 9 per cent). Mammaglobin expression was detected in four (13 per cent) of 31 patients with histologically negative sentinel nodes (95 per cent c.i. 4 to 30 per cent) and in six (14 per cent) of 44 patients with histologically negative non-sentinel nodes (95 per cent c.i. 5 to 27 per cent). The false-negative rate for sentinel node biopsy was zero using histology results and 10 per cent using RT-PCR. RT-PCR screening of axillary nodes for mammaglobin expression increased the detection of breast cancer metastases compared with routine histology.

Positron emission tomography detection of breast cancer metastasis to the uterus

BACKGROUND: We report the case of a patient presenting with moderate elevation of the tumor marker cancer antigen 15.3 during breast cancer follow-up. CASE: After a negative standard metastatic work-up, a positron emission tomography scan identified a localized central pelvic zone of uptake. Hysterectomy was performed, and pathology revealed a breast cancer metastasis within a previously known uterine leiomyoma. Positron emission tomography allowed assessment of soft tissues. CONCLUSION: With high sensitivity and specificity, positron emission tomography can be used to localize breast cancer metastases suspected by the presence of elevated serum tumor marker but not detected on standard metastatic workup.

Reverse transcription-polymerase chain reaction assay for multiple mRNA markers in the detection of breast cancer metastases in sentinel lymph nodes.

The identification of specific tumor mRNA markers by reverse transcription-polymerase chain reaction might be a valuable diagnostic adjunct for the detection of breast cancer metastases in axillary sentinel lymph nodes (SLNs). In this study we have compared the diagnostic accuracy of an extensive histopathologic examination of 146 SLNs from 123 breast carcinoma patients with that of the evaluation of 5 mRNA markers. When analyzed individually, none of the different markers attained a sensitivity higher than 77.8%, and the general concordance with the histopathologic findings ranged from 78.8 to 83.6%. In a multiple-marker assay, taking into account the expression of at least 1 of the 5 tumor markers, the sensitivity of the test rose to 95.6%, with a specificity of 66.3% and a general concordance with the histopathologic status of 75.3%. Finally, when at least 2 of 3 markers (maspin, cytokeratin 19 and mammaglobin 1) were expressed, the concordance with either SLN or axillary lymph node status was highest (88.4% and 84.6%, respectively). The high prevalence of positive reverse transcription-polymerase chain reaction assays in histologically uninvolved SLNs, however, may hamper extensive application of these techniques in the clinical setting.

Quantitative real-time RT-PCR detection of breast cancer micrometastasis using a multigene marker panel.

Real-time RT-PCR is a relatively new technology that uses an online fluorescence detection system to determine gene expression levels. It has the potential to significantly improve detection of breast cancer metastasis by virtue of its exquisite sensitivity, high throughput capacity and quantitative readout system. To assess the utility of this technology in breast cancer staging, we determined the relative expression levels of 12 cancer-associated genes (mam, PIP, mamB, CEA, CK19, VEGF, erbB2, muc1, c-myc, p97, vim and Ki67) in 51 negative-control normal lymph nodes and in 17 histopathology-positive ALNs. We then performed a receiver operating characteristic (ROC) curve analysis to determine the sensitivity and specificity levels of each gene. Areas under the ROC curve indicated that the most accurate diagnostic markers were mam (99.6%), PIP (93.3%), CK19 (91.0%), mamB (87.9%), muc1 (81.5%) and CEA (79.4.0%). mam was overexpressed in 16 of 17 lymph nodes known to contain metastatic breast cancer at levels ranging from 22- to 2.8 x 10(5)-fold above normal mean expression, whereas PIP was overexpressed from 30- to 2.2 x 10(6)-fold above normal in 13 lymph nodes. Real-time RT-PCR analysis of pathology-negative LN from breast cancer patients revealed evidence of overexpression of PIP (6 nodes), mam (3 nodes) and CEA (1 node) in 8 of 21 nodes (38%). Our results provide evidence that mam, PIP, CK19, mamB, muc1 and CEA can be applied as a panel for detection of metastatic and occult micrometastatic disease.

Histopathological detection of lymph node metastases from colorectal carcinoma

Aim—To evaluate whether the assessment of multiple sections from retrieved nodes yields an increased number of metastases compared with the number that would be detected by the commonly applied method...

Detection of Breast Cancer Metastases in the Cervical Spine

Thirty women with breast cancer and indications of possible cervical spine metastases underwent skeletal scintigraphy, conventional radiography, MR imaging and CT. By combining all examinations a diagnosis was settled in each patient and the different imaging techniques were compared. For all of the 26 patients with metastases in the cervical spine the correct diagnosis was found with MR imaging and CT. Both modalities also revealed paravertebral tumour growth, MR (n = 8) more than CT (n = 3). The sensitivity of skeletal scintigraphy in detecting metastases in the cervical spine was rather low, but as these examinations cover the whole body they are still convenient screening procedures, and combined with conventional radiography of selected areas are probably sufficient in many cases. Supplementary examinations with CT or MR would be valuable in patients with equivocal findings at screening for metastases or with clinical indications of metastases that remain unexplained after scintigraphy and radiography.

Detection of Breast Cancer Metastases in the Cervical Spine

Detection of Breast Cancer Metastases in the Cervical Spine

The value of the tumor marker CA 15-3 in diagnosing and monitoring breast cancer. A comparative study with carcinoembryonic antigen

To estimate the utility of the tumor-associated antigen CA 15-3 in the diagnosis of patients with breast cancer, this tumor marker was measured preoperatively in 1342 patients. This group included 509 patients with malignant disease (134 breast cancer patients and 375 patients with other malignancies not involving the breast) and 833 patients with benign surgical diseases (95 patients with fibroadenoma of the breast and 738 patients with other benign diseases). The results were compared with those obtained for carcinoembryonic antigen (CEA) in the diagnosis of breast cancer. The CA 15-3 level was above normal (25 U/ml) in 31% of the patients with breast cancer, in 22% of patients with other malignancies, and in 9% of patients with benign diseases. The CEA level was elevated in 26% of patients with breast cancer (more than 3 ng/ml). There was a good correlation of CA 15-3 levels with the tumor stage of breast cancer. Both CA 15-3 and CEA also were determined in 671 patients who had received initial curative surgery of breast cancer and who regularly attended our follow-up clinic. The CA 15-3 was found to be more sensitive than CEA in detecting recurrences of breast cancer. In the postcare period, carcinoma recurred in 205 patients. Of these, 73% had CA 15-3 concentrations above 25 U/ml; only 50% had CEA values above 3 ng/ml (P less than 0.0001). Although neither CA 15-3 nor CEA were sensitive enough for the screening and diagnosis of early breast cancer, CA 15-3 was significantly better than CEA in the detection of breast cancer metastases.

Breast cancer metastasis: W. A. Coventry, Duluth, Minn. American Journal of Obstetrics and Gynecology, July, 1926

Breast cancer metastasis accounts for the majority of deaths from breast cancer. Detection of breast cancer metastasis at the earliest stage is important for the management and prediction of breast cancer progression. Emerging techniques using the analysis of circulating tumor cells show promising results in predicting and identifying the early stages of breast cancer metastasis in patients. Additionally, a deeper understanding of the metastatic cascade in breast cancer will be critical for developing therapeutic interventions to combat breast cancer metastasis. In this review, the current and novel methods for detection of breast cancer metastasis, as well as the mechanisms involved in metastasis and the treatment of breast cancer metastasis, are discussed.