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221. VEGF and nitric oxide metabolites as markers of lymph node metastases in early breast carcinoma
S92 220. Predictive value of serum HER2 and CA 15-3 in patients with HER2 positive breast cancer and relapse of the disease: Preliminary study F. Lumachi1, L. Foltran2, M. Bonamini3, G.B. Chiara3, S.M.M. Basso3 1 University of Padova School of Medicine, Surgery Oncology & Gastroenterology, Padova, Italy 2 S. Maria degli Angeli Hospital, Medical Oncology, Pordenone, Italy 3 S. Maria degli Angeli Hospital, Surgery 1, Pordenone, Italy Background: Cancer antigen (CA) 15-3 is encoded by the MUC1 gene. It is overexpressed in breast cancer (BC) tissue, and released into the bloodstream. The human-epidermal-growth-factor receptor 2 (HER2) is a transmembrane glycoprotein with intracellular tyrosine kinase activity, that can also be measured in the blood. The role of circulating HER2 and CA 15-3 as predictive markers of relapse of the disease and in monitoring therapy in patients with metastatic BCare not well defined. The aim of this study was to analyze whether a correlation exists between preoperative serum CA 15-3 and HER2, and relapse of the disease in patients who underwent surgery for tissue HER2 positive (HER2+)BC. Materials and Methods: Data regarding a series of 12 women (median age 57 years, range 35-62 years) with stage I (pT1, N0-1mi, M0) tissue HER2+ BC (Group 1) who developed locoregional or distant metastases during follow-up were reviewed. Controls were 14 women with age- and stage-matched tissue HER2+ BC (Group 2) who did not developed relapse of the disease. All patients underwent preoperative CA 15-3 and HER2serum levels measurement, by a two-site sandwich immunoassay using direct chemiluminescent technology, and enzymelinked immunosorbent assay (ELISA), respectively. A serum CA 15-3 and HER2 concentration of 30 U/mL and 15 ng/mL were defined as the upper limit of normal, respectively. A p-value<0.05 was considered statistically significant. Results: Overall, the mean preoperative CA 15-3 and HER2 levels were 26.010.8 U/mL, and 18.59.3 ng/mL, respectively. CA 15-3 and HER2were above the cut-off in 7 and 10 patients of Group 1, respectively. The sensitivity, specificity, positive predictive value (PPV), negative predictive value, and negative likelihood ratio weighted by prevalence were (CA15-3 vs.HER2) 0.78 vs 0.77 (p¼0.86), 0.70 vs. 0.85 (p¼0.011), 0.58 vs. 0.83 (p<0.001),0.85 vs. 0.78 (p¼0.20), and 0.17 vs. 0.27 (p¼0.08), respectively. A weak correlation between CA 15-3 and HER2 (R¼0.46, p¼0.05) was found. There was no significant relationship between age of the patients, CA 15-3 (R¼-0.28, p¼0.25)or HER2 (R¼0.02, p¼0.92). Conclusions: In patients with stage I BC HER2+ BC, baseline serum CA 15-3 and HER2 are independent of age. Both have low sensitivity in detecting primary tumor, but the specificity and PPV of HER2 were significantly higher than that of CA 15-3. Those serum markers do not condition the therapeutic decision-making of patients, but are useful as prognostic factor in patients who will develop locoregional or distant metastases during follow-up. No conflict of interest. http://dx.doi.org/10.1016/j.ejso.2014.08.214
221. VEGF and nitric oxide metabolites as markers of lymph node metastases in early breast carcinoma K. Franciszkiewicz-Pietrzak1, A. Kurylcio1, J. Mielko1, B. Cisel1, M. Sk orzewska1, J. Kurzepa2, W.P. Polkowski1 1 Medical University of Lublin, Department of Surgical Oncology, Lublin, Poland 2 Medical University of Lublin, Chair and Department of Medical Chemistry, Lublin, Poland Background: Serum concentrations of vascular endothelial factor (VEGF) and nitrate/nitrite are raised in breast cancer patients showing correlation with the clinical stage of the disease. However, the measurement of the unbound fraction of VEGF and its isoform C (VEGF-C) in relation to nitric oxide metabolites (NOx) may give in-depth insight into the role of
ABSTRACTS those compounds in the pathogenesis of breast cancer growth and metastasis. Aim of the study is to investigate correlation between serum levels of free VEGF, VEGF-C and NOx and clinical and pathological features of non-metastatic breast cancer. Material and Methods: The study groups consisted of 45 female patients with breast cancer from 32 to 77 years old, 55 median. The control group included 14 healthy female volunteers from 34 to 72 years old, 48 median. Tumour staging was based on the 7th edition of the TNM classification according to the UICC. The involvement of lymph nodes and the histological types were determined by the post-operative pathological examination of the surgical specimens. Breast cancer patients were divided into two subgroups based on lymph node involvement and labelled as ’non-metastatic’ (n¼29) and ’metastatic’ (n¼16) groups. Preoperative serum samples were collected and free VEGF and VEGF-C were measured using ELISA assays while total NOx with the colorimetric vanadiumbased assay. Results: The serum NOx (p¼0.01) and VEGF-C (p¼0.01) but not of VEGF (p>0.05) levels were significantly higher in breast cancer group compared to controls. The sub-group analysis revealed that the NOx (p<0.05) and VEGF-C (p<0.01) concentrations were the highest in metastatic patients as compared to controls. There was no significant overall correlation between NOx and VEGF-C and total free VEGF concentrations in entire group of breast cancer patients. In the sub-group analysis, there was significant association between NOx and VEGF-C in the metastatic sub-group (r¼0.5; p¼0.04), but not in the non-metastatic sub-group (p>0.05). Conclusion: These findings indicate that VEGF-C and NOx, but not VEGF, are associated with lymph node metastases, especially in the early breast cancer. Further research on larger sample size is needed in order to elucidate the potential of these markers of early lymphatic spread in breast carcinoma. No conflict of interest. http://dx.doi.org/10.1016/j.ejso.2014.08.215
222. Predictors of sentinel lymph node metastases in women with early breast cancer in India K. Ashwin1 1 Manipal Comprehensive Cancer Center, Surgical Oncology, Bangalore, India Introduction: The presence of axillary lymph node metastases is an important prognostic factor in breast cancer and guides the surgeon to the appropriate therapy. Sentinel lymph node biopsy (SLNB) is an emerging method for the staging of the axilla in India. Although SLN biopsy is widely accepted as a minimally invasive method of nodal staging, failure to identify an SLN mandates a level I/II axillary node dissection and associated morbidity. The objective of this study was to elucidate various clinical, pathological and immunohistochemical factors that independently predict axillary lymph node involvement in early breast cancer in the Indian population. With these factors, we will be better able to identify groups of patients most likely to benefit from SLNB. Materials and Methods: 228 consecutive patients of both sex, with cytology or biopsy proven carcinoma breast, clinical stage T1/T2 N0 M0 at were subjected to SLNB and intra operative frozen examination. Age of the patient and primary tumor characteristics like size, grade, lymphovascular invasion (LVI), perineural invasion, ER/PR status, Her2-neu status and histological sub-types were evaluated for predicting the SLN metastasis. Results: Incidence of nodal metastases was correlated with clinicopathological factors and analyzed by univariate and multivariate analyses. The age of the patient ranged from 23 to 87 years and its association with SLN spread was not significant. Primary tumor characteristics like histological subtypes, grade (P ¼ 0.353), ER/PR status (P ¼ 0.839), Her2-neu status (P ¼0.296) were not significantly associated with SLN metastasis.
221. VEGF and nitric oxide metabolites as markers of lymph node metastases in early breast carcinoma K. Franciszkiewicz-Pietrzak1, A. Kurylcio1, J. Mielko1, B. Cisel1, M. Sk orzewska1, J. Kurzepa2, W.P. Polkowski1 1 Medical University of Lublin, Department of Surgical Oncology, Lublin, Poland 2 Medical University of Lublin, Chair and Department of Medical Chemistry, Lublin, Poland Background: Serum concentrations of vascular endothelial factor (VEGF) and nitrate/nitrite are raised in breast cancer patients showing correlation with the clinical stage of the disease. However, the measurement of the unbound fraction of VEGF and its isoform C (VEGF-C) in relation to nitric oxide metabolites (NOx) may give in-depth insight into the role of
ABSTRACTS those compounds in the pathogenesis of breast cancer growth and metastasis. Aim of the study is to investigate correlation between serum levels of free VEGF, VEGF-C and NOx and clinical and pathological features of non-metastatic breast cancer. Material and Methods: The study groups consisted of 45 female patients with breast cancer from 32 to 77 years old, 55 median. The control group included 14 healthy female volunteers from 34 to 72 years old, 48 median. Tumour staging was based on the 7th edition of the TNM classification according to the UICC. The involvement of lymph nodes and the histological types were determined by the post-operative pathological examination of the surgical specimens. Breast cancer patients were divided into two subgroups based on lymph node involvement and labelled as ’non-metastatic’ (n¼29) and ’metastatic’ (n¼16) groups. Preoperative serum samples were collected and free VEGF and VEGF-C were measured using ELISA assays while total NOx with the colorimetric vanadiumbased assay. Results: The serum NOx (p¼0.01) and VEGF-C (p¼0.01) but not of VEGF (p>0.05) levels were significantly higher in breast cancer group compared to controls. The sub-group analysis revealed that the NOx (p<0.05) and VEGF-C (p<0.01) concentrations were the highest in metastatic patients as compared to controls. There was no significant overall correlation between NOx and VEGF-C and total free VEGF concentrations in entire group of breast cancer patients. In the sub-group analysis, there was significant association between NOx and VEGF-C in the metastatic sub-group (r¼0.5; p¼0.04), but not in the non-metastatic sub-group (p>0.05). Conclusion: These findings indicate that VEGF-C and NOx, but not VEGF, are associated with lymph node metastases, especially in the early breast cancer. Further research on larger sample size is needed in order to elucidate the potential of these markers of early lymphatic spread in breast carcinoma. No conflict of interest. http://dx.doi.org/10.1016/j.ejso.2014.08.215
222. Predictors of sentinel lymph node metastases in women with early breast cancer in India K. Ashwin1 1 Manipal Comprehensive Cancer Center, Surgical Oncology, Bangalore, India Introduction: The presence of axillary lymph node metastases is an important prognostic factor in breast cancer and guides the surgeon to the appropriate therapy. Sentinel lymph node biopsy (SLNB) is an emerging method for the staging of the axilla in India. Although SLN biopsy is widely accepted as a minimally invasive method of nodal staging, failure to identify an SLN mandates a level I/II axillary node dissection and associated morbidity. The objective of this study was to elucidate various clinical, pathological and immunohistochemical factors that independently predict axillary lymph node involvement in early breast cancer in the Indian population. With these factors, we will be better able to identify groups of patients most likely to benefit from SLNB. Materials and Methods: 228 consecutive patients of both sex, with cytology or biopsy proven carcinoma breast, clinical stage T1/T2 N0 M0 at were subjected to SLNB and intra operative frozen examination. Age of the patient and primary tumor characteristics like size, grade, lymphovascular invasion (LVI), perineural invasion, ER/PR status, Her2-neu status and histological sub-types were evaluated for predicting the SLN metastasis. Results: Incidence of nodal metastases was correlated with clinicopathological factors and analyzed by univariate and multivariate analyses. The age of the patient ranged from 23 to 87 years and its association with SLN spread was not significant. Primary tumor characteristics like histological subtypes, grade (P ¼ 0.353), ER/PR status (P ¼ 0.839), Her2-neu status (P ¼0.296) were not significantly associated with SLN metastasis.