Preoperative CA 15.3 and prognosis in primary breast cancer

CA15.3 is a breast cancer-associated antigen encoded by the MUC-1 gene. The clinical applications of CA 15.3 are the monitoring of response in advanced breast carcinoma and the early detection of recurrences. We have investigated the prognostic value of CA 15.3 in primary breast cancer. Preoperative serum CA 15.3 was measured in 478 patients with early breast cancer. Positive CA 15.3 was defined as > 30 U/ml. CA 15.3 positivity was correlated with patient outcome in terms of disease-free survival (DFS). Seven per cent of patients had elevated serum CA 15.3. A positive association was found between CA 15.3 positivity and tumour size. Twenty-one per cent of the patients with T3 and T4 tumours had high serum concentrations of CA 15.3; while only six per cent of patients with T1 and T2 tumours had elevated concentrations of CA 15.3 (p < 0.0001). There was no correlation between CA 15.3 serum levels and menopausal status, axilary lymph node status, estrogen receptor status, p53 and erbB-2 status, and CEA serum levels. With a median follow-up of 24 months, we found that elevated CA 15.3 levels predicted a poor clinical outcome. The probability of disease-free survival at two years was 73% in patients with high preoperative CA 15.3 compared with 90% in patients with normal CA 15.3 levels (logrank p = 0.003). The association of CA 15.3 with DFS was also analysed with a Cox analysis, and was found to be independent of tumour size. The multivariate analysis showed that poor disease-free survival was significantly associated with high CA 15.3 (p = 0.04), large tumour size (p = 0.001), estrogen receptor negative status (p = 0.008), overexpression of erbB-2 (p = 0.04), and overexpression of p53 protein (p = 0.03). Preoperative serum CA 15.3 is significantly related to clinical outcome in patients with early breast cancer. High CA 15.3 indicates a poor prognosis and this is independent from tumour size. Whether the poor prognosis associated with CA 15.3 is related with the role of mucins in the adhesion of cancer cells needs to be investigated.     

Is tissue polypeptide antigen still a useful tumor marker in breast carcinoma? Comparison with CA15.3 and MCA

Serum levels of tissue polypeptide antigen (TPA) are related to the proliferative activity and to the mass of the malignancy, differently from any other available tumor marker. We therefore evaluated TPA in comparison with CA15.3 and MCA (mucinous-like carcinoma-associated antigen) in patients with primary breast cancer. TPA was measured in tumor cytosol and in serum. Cytosol and serum TPA levels were not significantly correlated. Serum TPA was higher in patients with locally more advanced disease and in receptor-negative cases. The relation between TPA and disease spread was not directly dependent on tumor bulk, whereas CA15.3 and MCA were highly correlated to the number of positive lymph nodes and tumor size. No correlations were found between TPA and CA15.3 or MCA, and the positivity concordance rate between TPA and CA15.3 or MCA was very low. Patients with higher TPA serum levels showed a worse prognosis in cases with and in those without axillary metastases. From our data we conclude that TPA provides information different from that obtained with breast-specific tumor markers and could therefore be useful in association with CA15.3 and/or MCA in the management of patients with breast cancer.     

Expression of prostate-specific antigen (PSA) correlates with poor response to tamoxifen therapy in recurrent breast cancer

Prostate-specific antigen (PSA) is a serine protease which may play a role in a variety of cancer types, including breast cancer. In the present study, we evaluated whether the level of PSA in breast tumour cytosol could be associated with prognosis in primary breast cancer, or with response to tamoxifen therapy in recurrent disease. PSA levels were determined by enzyme-linked immunosorbent assay (ELISA) in breast tumour cytosols, and were correlated with prognosis in 1516 patients with primary breast cancer and with response to first-line tamoxifen therapy in 434 patients with recurrent disease. Relating the levels of PSA with classical prognostic factors, low levels were more often found in larger tumours, tumours of older and post-menopausal patients, and in steroid hormone receptor-negative tumours. There was no significant association between the levels of PSA with grade of differentiation or the number of involved lymph nodes. In patients with primary breast cancer, PSA was not significantly related to the rate of relapse, and a positive association of PSA with an improved survival could be attributed to its relationship to age. In patients with recurrent breast cancer, a high level of PSA was significantly related to a poor response to tamoxifen therapy, and a short progression-free and overall survival after start of treatment for recurrent disease. In Cox multivariate analyses for response to therapy and for (progression-free) survival, corrected for age/menopausal status, disease-free interval, site of relapse and steroid hormone receptor status, PSA was an independent variable of poor prognosis. It is concluded that the level of PSA in cytosols of primary breast tumours might be a marker to select breast cancer patients who may benefit from systemic tamoxifen therapy.     

Evaluation of soluble CD44 in patients with breast and colorectal carcinomas and non-Hodgkin's lymphoma.

CD44 is a transmembrane glycoprotein involved in cell-cell and cell-substrate interactions. As a cell surface molecule, CD44 may be shed or released into the circulation by proteolytic enzymatic mechanisms. Therefore, soluble CD44 can be found in cell culture supernatants as well as in plasma. In this study we evaluated the levels of soluble total CD44 (sCD44) in serum samples of patients with breast and colorectal carcinoma as well as non-Hodgkin's lymphoma in order to correlate prognosis with sCD44 expression. Besides, we evaluated other clinical tumour markers routinely used, Cancer Antigen (CA) 15.3 and CA 19.9. We investigated 132 serological samples from breast cancer patients, 48 sera from colorectal tumours, 48 samples from stage IV non-Hodgkin's lymphoma and sera from 80 individuals without evidence of cancer or autoimmune disease. Breast cancer patients were divided into three groups: a) patients with no clinical evidence of positive nodules and no metastatic disease; b) patients with positive nodules; and c) patients with metastasis. sCD44 mean serum levels in these groups were 198+/-54 ng/ml, 221+/-78 ng/ml and 242+/-119 ng/ml, respectively, while the marker CA 15.3 values were 15.6+/-6.6 U/ml, 14.0+/-5.8 U/ml and 211.5+/-358.9 U/ml, respectively. sCD44 levels for colorectal tumour were 243+/-72 ng/ml, while CA 19.9 serum levels were 230+/-270 U/ml. Stage IV non-Hodgkin's lymphoma sCD44 levels were 398+/-160 ng/ml. sCD44, CA 15.3 and CA 19.9 values for healthy individuals without evidence of any cancer pathology were 223+/-58 ng/ml, 16.4+/-6.2 U/ml and 33+/-14 U/ml, respectively. From these results we conclude that sCD44 might be used as a reliable marker for patients with non-Hodgkin's lymphoma. However, sCD44 levels failed to correlate with prognosis, tumour burden or metastasis in breast and colorectal cancer patients. Neither was any correlation found between high CA 15.3 or CA 19.9 levels and soluble CD44 serum level.     

CA27.29: a valuable marker for breast cancer management. A confirmatory multicentric study on 603 cases

Recently, a fully automated method has become commercially available to measure the MUC-1-associated antigen CA27.29. The present investigation was performed in order to compare CA27.29 and CA15.3 in a wide series of patients affected with breast cancer. Overall, 603 cases with breast cancer and 194 healthy controls were investigated. Patients were enrolled in 4 institutions, while assays were performed in one laboratory. CA27.29 was measured by the ACS:180 BR assay (Bayer Diagnostics) and CA15.3 by the AxSYM (Abbott Laboratories). An excellent correlation was found between the results obtained by the two methods. The two markers showed comparable results in healthy controls, with higher levels in post-menopausal than in pre-menopausal subjects. The markers were significantly higher in primary breast cancer than in controls. The areas under the receiver operating characteristics (ROC) curves of the two tests were comparable, but CA27.29 showed better sensitivity in cases with low antigen concentrations (below the cut-off point). Accordingly, when comparing each test in different stage categories, significance levels of the differences were higher for CA27.29 than for CA15.3 for all T categories versus healthy controls, for pT1 versus pT2, for all N categories versus healthy controls and for node-negative versus N1-3 patients. From the results of the present study, that has been performed on samples taken at diagnosis and prior to any treatment from the widest series of patients with primary breast cancer reported so far, we can draw the following conclusions: CA27.29 provides comparable results to CA15.3; CA27.29 seems more sensitive than CA15.3 to limited variations of tumour extension; however, it cannot help clinicians in distinguishing stage I patients from stage II patients. However, from the point of view of clinical decision making, CA27.29 provides comparable results to CA15.3. CA27.29 is therefore suitable for routine use in the management of patients with breast cancer.     

Serum CA549 in primary breast cancer: comparison with CA15.3 and MCA.

We carried out a comparison of three commonly used mucin markers, CA549, CA15.3 and MCA. Serum samples from 184 healthy women and 237 patients with primary breast cancer were evaluated. The markers were measured using commercially available immunometric assays. Like CA15.3 and MCA, CA549 was significantly associated with tumour size and lymph node status, being an effective indicator of tumour bulk. CA549 was significantly correlated with both CA15.3 and MCA. Positive/negative concordance rate was very good (93.7%) between CA549 and MCA. Conversely, CA15.3 was positive and CA549 negative in 20.4% of cases. Axillary status was not significantly different in the latter group of patients and in cases in which CA15.3 and CA549 showed concordant results. From the present findings we draw the following major conclusions: 1. CA549 and MCA are highly correlated and their association should not provide additional information; however, they should not be considered interchangeable since they may behave differently in individual cases. 2. CA549 and CA15.3, although well correlated, are discordant in a significant number of cases. Longitudinal studies are needed to verify the usefulness of the association between the two markers. 3. The three evaluated mucin markers are not interchangeable in individual patients; if a patient is monitored with a marker, she should be followed up with the same marker.     

Prognostic role of serum CA15.3 in 362 node-negative breast cancers. An old player for a new game

The aims of the present investigation were to evaluate the association between serum CA15.3 levels and other biological and clinical variables and its prognostic role in patients with node-negative breast cancer. We evaluated 362 patients operated upon primary breast cancer from 1982 to 1992 (median follow-up 69 months). Serum CA15.3 was measured by an immunoradiometric assay. The association between variables was investigated by a Principal Component Analysis (PCA) and the prognostic role of CA15.3 on relapse-free survival (RFS) was investigated by Cox regression models adjusting for age, oestrogen receptor (ER), tumour stage, and ER x age interaction, with both the likelihood ratio test and Harrell's c statistic. The prognostic contribution of CA 15.3 was highly significant. Log relative hazard of relapse was constant until approximately 10 (U/ml) of CA15.3 and increased thereafter with increasing marker levels. CA15.3 showed a significant contribution using as a cut-off point a value of 31 U/ml. However, the contribution to the model of the marker as a continuous variable is much greater. From these findings, we can conclude that: (i) CA15.3 is a prognostic marker in node-negative breast cancer; (ii) its relationship with prognosis is continuous, with the risk of relapse increasing progressively from approximately 10 U/ml.     

The analysis of prognostic factors in stage III-B non-inflammatory breast cancer.

AIMS: To evaluate factors predicting disease recurrence in patients treated for stage III-B breast cancer by neoadjuvant chemotherapy followed by surgery. METHODS: A retrospective study of 52 patients who responded to neoadjuvant chemotherapy followed by modified radical mastectomy was carried out. The parameters studied included pre-treatment tumour size, clinical axillary status, grade, lymphatic-vascular invasion, pathological axillary status, number of metastatic lymph nodes, menopausal status and oestrogen receptor status. RESULTS: In the univariate analysis, number of metastatic lymph nodes, primary tumour size, pathological axillary status and histological grade were statistically significant factors associated with recurrence of disease. Multivariate analysis demonstrated that the number of metastatic lymph nodes (relative hazard 6.1) and primary tumour size (related hazard 2.5) were the most important independent prognostic factors for recurrence. CONCLUSIONS: These results indicate that the number of involved lymph nodes after neoadjuvant chemotherapy, independent of the clinical response of primary tumour, had a most significant impact on disease free survival. Additionally primary tumour size had a marked prognostic significance in spite of clinical changes in tumours following chemotherapy.     

The H-ras oncogene product p21 and prognosis in human breast cancer

Summary The protein product of the H-ras oncogene, p21, has been measured semiquantitatively in solubilized particulate fractions of 160 primary tumours from patients presenting without evidence of distant metastatic breast cancer. Levels of p21 have then been related to factors of established prognostic significance, and to clinical outcome after primary treatment in terms of disease-free interval and survival times. p21 was detected by Western blotting in all tumour fractions, but amounts varied markedly between different tumours. There was no significant relationship between levels of p21 and the menopausal status of the patient, tumour oestrogen receptors, grade, and clinical stage. However, there was a significant trend for tumours to be associated with lymph node involvement as p21 was increasingly expressed. Elevated levels of p21 were also significantly related to early disease recurrence and death from cancer. Multivariate stepwise analysis showed that both p21 and lymph node status were independent statistically significant factors for disease recurrence and survival, and that no other parameter was significant for clinical outcome after adjustment for p21 and lymph node status. These results indicate that tumour levels of p21 are an important prognostic variable in patients with early breast cancer.     

Angiogenesis and hypoxia in lymph node metastases is predicted by the angiogenesis and hypoxia in the primary tumour in patients with breast cancer

Hypoxia and angiogenesis are important factors in breast cancer progression. Little is known of hypoxia and angiogenesis in lymph node metastases of breast cancer. The aim of this study was to quantify hypoxia, by hypoxia-induced marker expression levels, and angiogenesis, by endothelial cell proliferation, comparing primary breast tumours and axillary lymph node metastases. Tissue sections of the primary tumour and a lymph node metastasis of 60 patients with breast cancer were immunohistochemically stained for the hypoxia-markers carbonic anhydrase 9 (CA9), hypoxia-inducible factor-1alpha (Hif-1alpha) and DEC-1 and for CD34/Ki-67. Endothelial cell proliferation fraction (ECP%) and tumour cell proliferation fraction (TCP%) were assessed. On haematoxylin-eosin stain, the growth pattern and the presence of a fibrotic focus were assessed. Hypoxia-marker expression, ECP% and TCP% in primary tumours and in lymph node metastases were correlated to each other and to clinico-pathological variables. Median ECP% and TCP% in primary tumours and lymph node metastases were comparable (primary tumours: ECP%=4.02, TCP%=19.54; lymph node metastases: ECP%=5.47, TCP%=21.26). ECP% correlated with TCP% (primary tumours: r=0.63, P<0.001; lymph node metastases: r=0.76, P<0.001). CA9 and Hif-1alpha expression were correlated (primary tumours P=0.005; lymph node metastases P<0.001). In primary tumours, CA9 and Hif-1alpha expression were correlated with DEC-1 expression (P=0.05), presence of a fibrotic focus (P<0.007) and mixed/expansive growth pattern (P<0.001). Primary tumours and lymph node metastases with CA9 or Hif-1alpha expression had a higher ECP% and TCP% (P<0.003); in primary tumours, mixed/expansive growth pattern and fibrotic focus were characterised by higher ECP% (P=0.03). Furthermore, between primary tumours and lymph node metastases a correlation was found for ECP%, TCP%, CA9 and Hif-1alpha expression (ECP% r=0.51, P<0.001; TCP r=0.77, P<0.001; CA9 and Hif-1alpha P<0.001). Our data demonstrate that the growth of breast cancer lymph node metastases is angiogenesis dependent and that angiogenesis and hypoxia in the primary tumour predict angiogenesis and hypoxia in the lymph node metastases. Together with previous findings in breast cancer liver metastases, which grow in 96% of cases angiogenesis independently, these data suggest that both the intrinsic growth characteristics and angiogenic potential of breast cancer cells and the site-specific tumour microenvironment determine angiogenesis and hypoxia in breast cancer.     

Importance of the level of axillary involvement in relation to traditional variables in the prognosis of breast cancer.

Survival in breast cancer correlates with the presence of metastatic lymph nodes, so that removal and pathological examination of the axillary nodes provides the most important prognostic information and basis for planning subsequent therapy. However as the size of primary tumours at diagnosis is decreasing, the likelihood of axillary involvement is also declining, so that the indications for axillary dissection are undergoing radical revision. To definitively establish the value of removing all three axillary lymph node levels (as defined by Berg) in node positive breast cancer, retrospective analysis of a large series receiving complete dissection was carried out. consecutive breast cancer patients (n=1003) with positive axillary nodes were analyzed: all received identical axillary treatment and the three levels were tagged with metal disks to facilitate recognition and pathological examination. Follow-up (mean 97 months) was exceptionally complete. The length of disease-free and overall survival were taken as the primary endpoints. The variables considered in the statistical analysis were tumour size, number of metastatic nodes, axillary invasion by level (the three classic levels), perilymphnodal invasion and age. By univariate analysis, overall and disease-free survival decreased significantly as tumour diameter, number of involved lymph nodes, and involvement by axillary level increased. Multivariate analysis assessing the relative importance of these variables when all were considered together found that they were all important independent predictive factors for survival. This study confirms the importance of tumour size and number of metastatic axillary nodes as predictors of outcome in breast cancer. In addition, the level of axillary invasion as a third independent factor of equal importance to the established indicators was identified. When axillary dissection is performed it should be complete, and all three Berg levels tagged separately, so that involvement by level can be ascertained. This provides additional important prognostic information on which to base subsequent treatment decisions.     

Analysis of metastatic involvement of interpectoral (Rotter's) lymph nodes related to tumor location, size, grade and hormone receptor status in breast cancer

AIMS AND BACKGROUND: This study was aimed at analyzing metastatic involvement in interpectoral (Rotter's) lymph nodes in relation to tumor location, size, grade and hormone receptor status in primary breast cancer. METHODS: The study included 172 female patients undergoing surgery for breast cancer at the University Hospital for Tumors, Zagreb, Croatia from November 2001 to August 2003. In addition to the standard surgical procedure, interpectoral (Rotter's) lymph nodes were removed in all of the patients. Serum levels of the tumor marker CA 15-3 were determined before surgery and hormone receptor status after surgery. RESULTS: Rotter's lymph nodes were identified in 67% of the patients, with metastatic involvement being found in 20% of the Rotter's nodes. Metastatic involvement of Rotter's nodes in patients with negative and positive axillary lymph nodes was 4% and 35%, respectively. When we looked at the location of the tumor in patients with metastatic involvement of Rotter's nodes, we found that tumors located in the upper quadrants were more prone to metastasis to Rotter's nodes; there was a significant positive correlation between tumor location and positive Rotter's nodes (r = 0.953, P = 0.012). As regards tumor size, Rotter's nodes were identified in 15%, 20% and 30% of stage T1 (< 2 cm), T2 (2-5 cm) and T3 (> 5 cm) tumors, respectively. Hormone receptor status showed no statistically significant difference in the expression of estrogen and progesterone receptors between patients with and those without positive Rotter's nodes. Of 35 Rotter's node-positive patients, 31.4% had elevated serum levels of CA 15-3; the level was significantly higher in Rotter's-positive patients compared to those with negative (or absent) Rotter's nodes. CONCLUSIONS: The results show that one-fifth of breast cancer patients, or even one-third of those with positive axillary lymph nodes, are discharged with positive interpectoral lymph nodes that remain undiagnosed. As the nodes can be surgically removed without additional mutilation, exploration of Rotter's lymph nodes should be introduced into routine clinical practice.     

Immunohistochemically defined subtypes and outcome in occult breast carcinoma with axillary presentation

The aim of this study is to evaluate the outcome of occult breast cancer (OBC) in patients with axillary presentation overall and according to the immunohistochemically defined tumour subtypes. We reviewed information on 15,490 consecutive primary breast cancer patients, who underwent surgery at the European institute of oncology between September 1997 and December 2008. Patients with OBC were compared with an equal number of patients with small invasive breast carcinomas (pT1) observed at the same institution during the same period, matched for year of surgery, age, nodal status and biological features. Eighty patients with OBC (study group) and 80 patients with early breast cancer (control group) were identified. There was no significant difference in the disease-free survival (5 years DFS 66 vs. 68% P = 0.91) and the overall survival (5 years OS 80 and 86% P = 0.99) between the OBC and control groups. A statistically significant worse outcome was observed within the group of OBC for patients with more than four involved lymph nodes and with triple negative tumours. The outcome of OBC patients is comparable with that of matched patients with small sized breast cancer. High risk of relapse and death was observed in OBC patients with triple negative tumours and extensive nodal involvement.     

Expression of metalloproteinases MMP-2 and MMP-9 in sentinel lymph node and serum of patients with metastatic and non-metastatic breast cancer

The objective of this study was to evaluate the expression of MMP-2 and MMP-9 in sentinel lymph node and serum of breast cancer patients in order to evaluate their clinical significance and usefulness as diagnostic tumour markers. Expression of MMP-2 and MMP-9 was performed on sentinel lymph node by immunohistochemistry while gelatine zymography was used to determinate the serum expression. The association of gelatinases with clinicopathological features, were analysed. Metastatic and non-metastatic breast cancer patients and 34 healthy women were involved. Gelatinases expression were significantly higher in metastatic breast cancer in comparison to non-metastatic cancer and the control group both in the sentinel lymph node and serum. Results showed a statistically significant correlation between MMP-2 or MMP-9 and cancer familiality, MMP-9 and CA 15.3 levels, and MMP-9 and grading. This study suggests a clinical utility of these proteolytic markers in malignant tumour, growth, invasion and metastasis in breast cancer.     

Pattern of spread and progression in relation to the characteristics of the primary tumour in human breast cancer

Characteristics of primary breast tumours were related to the extent of dissemination, the anatomical location of metastases, and the rate of progression in 863 patients with recurrent breast cancer. The following features were examined: tumour laterality, location within the breast, size, invasion of skin or fascia, presence of residual cancer tissue (RCT) in the mastectomy specimen, and number of positive lymph nodes. Increasing tumour size, increasing number of nodes, and the presence of local invasion and RCT were all associated with a short duration of survival both from initial diagnosis and from first recurrence. None of the factors were related to either the extent of dissemination or the rate of progression. Patients who had their primary tumours located in the medial or central part of the breast had an increased incidence of mediastinal and pleural recurrences respectively. Primary tumours greater than 5 cm, invasion of skin or fascia, and presence of RCT were all associated with an increased incidence of local recurrences. In addition, both RCT and fascial invasion were associated with increased occurrence of brain metastases. Most differences were explainable on the basis of local and regional lymphodynamics. Since the status of the features examined here all vary with time from tumour inception, it is suggested that the impact on prognosis is related to variations in tumour age from inception to primary diagnosis rather than to qualitative biological differences.     

糖类抗原125、糖类抗原153水平与乳腺癌患者临床特征及预后的关系

目的 探讨糖类抗原125(CA125)、糖类抗原153(CA153)水平与乳腺癌患者临床特征及预后的关系.方法 选取220例乳腺癌患者(乳腺癌组)及同期收治的100例健康体检者(健康对照组),比较两组患者血清CA125、CA153水平,比较不同临床特征乳腺癌患者血清CA125、CA153阳性率,并对乳腺癌患者进行为期5...     

An evaluation of the usefulness of primary tumour expression of MCA and CA15-3 as prognostic indicators in breast carcinoma.

CA15-3 antigen and mucin-like carcinoma associated antigen (MCA) show potential as clinically useful serum markers of breast carcinoma. Recently, immunohistochemical versions of these monoclonal antibodies have become available but few data are available as to their clinical usefulness. The aims of this study were (i) to assess CA15-3 and MCA expression by primary breast tumours and to correlate tumour immunoreactivity with tumour behaviour, and (ii) to investigate the relationship between immunohistological staining and oestrogen receptor (ER) status. Pathological material from 39 stage 1 (node free) breast carcinoma patients was assessed. The mean age was 51.3 (range 34-70) years, 19 were premenopausal and the mean duration of follow-up was 3.6 years (range 0.8-14 years). In each case two further sections were stained with antisera to the CA15-3 and MCA antigens. Staining of primary tumour was achieved in 38 cases. Low (less than 30% tumour cell staining) and intermediate (30-60% of cells staining) grade immunoreactivity with both monoclonals correlated with significantly shorter disease free intervals (P less than 0.05). Neither monoclonal can predict ER status. We conclude that the use of monoclonal antibodies to CA15-3 and MCA in staining primary breast carcinoma tumours and their axillary nodes may be a significant (P less than 0.05) prognostic indicator of future tumour behaviour and that this requires further evaluation.     

Evaluation of tumor markers (HER-2/neu oncoprotein,CEA, and CA 15.3) in patients with locoregional breast cancer: prognostic value

Tumor markers were studied in the sera of 883 untreated patients with primary breast cancer diagnosed between 1989 and 2007. Abnormal human epidermal growth factor receptor 2 (HER-2)/neu levels (>15 ng/mL) were found in 9.5%, carcinoembryonic antigen (CEA) in 15.9%, and cancer antigen (CA) 15.3 in 19.7% of the patients. One or more tumor markers were abnormal in 305 (34.5%) of the 883 studied patients. Significantly higher serum HER-2/neu levels were found in patients with tissue overexpression of this oncoprotein (p < 0.0001). CEA, CA 15.3, and HER-2/neu (only in those patients with tissue overexpression) serum levels were related with tumor stage (tumor size and nodal involvement) and steroid receptors (higher values in estrogen receptor-negative (ER−) tumors). Univariate analysis showed that HER-2/neu serum levels were prognostic factors in disease-free survival (DFS) and overall survival (OS) only in patients with tissue overexpression. Multivariate analysis in 834 patients show that nodal involvement, tumor size, ER, CEA, and adjuvant treatment were independent prognostic factors in DFS and OS. When only patients with HER-2/neu overexpression in tissue were studied, tumor size, nodal involvement, and tumor markers (one or another positive) were independent prognostic factors for both DFS and OS. HER-2/neu serum levels were also an independent prognostic factor, with CEA, ER, and nodes in 106 patients treated with neoadjuvant treatment. In summary, serum HER-2/neu, CEA, and CA 15.3 are useful tools in the prognostic evaluation of patients with primary breast cancer.     

Axillary lymph-node dissection for positive sentinel nodes in breast cancer patients.

AIM: The aim was to identify a subset of breast cancer patient with positive sentinel nodes (SNs) for whom secondary axillary clearance would be unnecessary.METHODS: Between March 1999 and May 2001, 288 patients with T0-T2 breast cancer less than 3cm in diameter had SN detection either by a colorimetric method or using a combined technique. SNs were stained with haematoxylin and eosin (H&E). For all negative SNs, serial sections and immunochemistry (IHC) were performed. All patients with positive SNs underwent a complete axillary lymph node dissection. One hundred and twenty patients were SN positve.RESULTS: Non-sentinel node positivity (NSNP) was closely associated with the size of the tumour (14.3%, 54.1% and 51.8% for pT1a-b, pT1c and pT2 tumours respectively) and with the size of the SN metastasis: 15.9% IHC detected micrometastasis, 33.3% and 78.8% micro- and macrometastasis detected with H&E staining respectively. NSNP was found in 24.0% and 42.8% of patients with pT1c breast cancer and with micrometastasis detected by IHC and H&E staining. The node positivity rate reached 81.1% for pT1c lesions with macrometastasis in the SN. For the patients with pT2 breast cancer, these rates were 12.5% (IHC), 28.5% (H&E) 91.1% (macrometastasis).CONCLUSIONS: We are unable to isolate precisely a subset of patients for whom total axillary lymph node dissection would be unnecessary. A subset of 14 small tumours (<1cm diameter) demonstrated micrometastases in the SN without NSNP.     

Significance of vascular endothelial growth factor,interleukin-18 and nitric oxide in patients with breast cancer: correlation with carbohydrate antigen 15.3

The aim of this study was to determine serum concentrations of angiogenic factors including vascular endothelial growth factor (VEGF), interleukin 18 (IL-18) and nitric oxide (NO) in patients with breast cancer and to evaluate whether these factors will be correlated with CA 15.3, as a routine tumor marker for breast cancer or not. This study was conducted on 44 patients with breast cancer and 15 healthy individuals as a control group. The results demonstrated significant increase in serum IL-18, NO and CA 15.3 levels in sera of breast cancer patients when compared to those of the control group (P < 0.001, P = 0.016 and P < 0.001, respectively). However, the mean serum level of VEGF in patients as showed insignificant increase compared to that of the controls was not significant (P = 0.311). Sensitivity of CA 15.3, VEGF, IL-18 and NO to detect patients with disease was 52.2, 21.3, 77.2 and 70.4 %, respectively. In addition, positive status of serum CA 15.3 and/or IL-18 was found in 39 out of 44 (88.6 %) patients, and the positive status of serum CA 15.3 and/or NO was only found in 35 out of 44 (79.5 %). In conclusion, the simultaneous determination of IL-18 or NO in combination with the CA 15.3 may increase the sensitivity to diagnose breast cancer and may aid in disease prognosis.