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222. Predictors of sentinel lymph node metastases in women with early breast cancer in India
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.
ABSTRACTS Size of the primary tumor (P ¼ 0.002), LVI (P < 0.001), perineural invasion (P ¼ 0.084+) were significant factors determining the SLN metastasis Conclusions: The status of the axillary lymph nodes is one of the most important prognostic factors in women with early stage breast cancer. Size of the primary tumor, LVI and perineural invasion were significant factors determining the SLN metastasis. We have found independent preoperative predictive factors in our local population for the presence of nodal metastases. This information can aid patient selection for SLNB and improve patient counselling. No conflict of interest.
S93 Results. 200 consecutive patients, mean age 61 (range 28-99), were studied. 112(56%) did not meet any criteria for screening/ intervention. 88 (44%) met criteria either for screening in 55, and or family history assessment in 33. 57/88 (64.8%) meeting criteria did not have a mammogram or risk assessment. The stage of breast cancer was significantly earlier in those falling within guidelines, with early stage in n¼114 (79.7%) and late in n¼29 (20.3%), compared to early in 63.2% and late in 36.8% of those failing to be screened appropriately (p¼0.01 c2 df1). Conclusion. This study identified the hazards of not been screened with resultant late diagnosis and negative prognostic implications. No conflict of interest.
http://dx.doi.org/10.1016/j.ejso.2014.08.216 http://dx.doi.org/10.1016/j.ejso.2014.08.218 223. Primary small cell carcinoma of the breast K. Park1, M.J. Jung2, S.I. Yang1 1 Kosin University College of Medicine, Department of Surgery, Busan, South Korea 2 Kosin University College of Medicine, Department of Pathology, Busan, South Korea Background: Primary SCC of the breast accounts for less than 1% of primary breast cancers. Due to the rarity of this type of tumor and the lack of a standard treatment, we report here a case study of primary SCC of the breast and discuss its clinicopathologic characteristics. Methods: A 58-year-old female patient presented with a painless mass in right breast for 2 months. An ultrasound scan revealed two solid and low heterogeneous echoes in the left breast: one was in the 3 o’clock position, 35 mm away from the nipple. A mass was poorly defined with irregular borders. She underwent modified radical mastectomy with axillary lymph node dissection. Microscopically, the mass (in the 3 o’clock position, 35 mm away from the nipple) was about 2.2 cm 1.8 cm 1.6 cm, which was diagnosed histologically small cell carcinoma with glandular differentiation. Immunohistochemically, tumor cells were negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) and histological examination also demonstrated 1 positive lymph node out of 25 axillary lymph nodes. The patient was scheduled to receive systemic chemotherapy with doxorubicin-cyclophosphamide followed by docetaxel (AC / T) every 3 weeks (60 mg/m2 doxorubicin, 600 mg/m2 cyclophosphamide and 75 mg/m2 docetaxel). Results: The patient is currently free of disease 50 months after operation with adjuvant chemotherapy. Conclusions: In this report, we describe a case of primary small cell carcinoma of the breast. No conflict of interest. http://dx.doi.org/10.1016/j.ejso.2014.08.217
224. Failure to engage in breast screening and risk assessment results in more advanced stage at diagnosis M. Sugrue1, A. Johnston1, S. Curran1 1 Letterkenny General Hospital, Breast Centre North West, Co Donegal, Ireland Introduction. Population based screening and family risk assessment for breast cancer while well established, has come under scrutiny recently. The concept of over-diagnosis is topical in recent cancer publications. This study assessed the impact of failure to screen or risk assess patients attending a designated breast cancer unit with a newly diagnosed breast cancer. Methods. A retrospective review was undertaken of 200 consecutive patients with breast cancer between January 2010 - September 2012 at Letterkenny Hospital. Appropriate screening was defined as biennial in those aged 50-66 and 40-49 with moderate / high family history risk (NICE criteria or IBIS criteria). Patient demographics, diagnosis date, stage (TNM) were documented. Patients with previous breast cancer were not included (n¼6).
225. Annexin A3 is a breast cancer marker secreted by neoplastic cell lines and is involved in cell migration B. Zeidan1, T. Jackson2, S. Larkin1, R. Cutress1, M. Ashton-Key1, G. Packham1, S. Garbis1, P. Townsend2 1 University of Southampton, Cancer Sciences, Southampton, United Kingdom 2 University of Manchester, Cancer Sciences, Manchester, United Kingdom Background: This study was designed to identify and functionally characterise potential breast cancer biomarkers in patients prior to intervention. Materials and methods: We used mass spectrometry (MS) to analyse serum samples representing 630 controls, 192 benign breast disease (BBD) and 219 invasive breast cancer (IDC) patients prior to intervention. Using liquid chromatography, free-flow electrophoresis (FFE), and immunoprecipitation isolation and purification techniques followed by the combined use of mass spectrometry (MS) tools with enzyme-linked immunosorbent assay (ELISA) validation we identified potential biomarkers. The diagnostic value of serum biomarkers were subsequently validated by ELISA in an independent serum set, as well as breast tissue from samples representing the three groups. The functional role of markers were also investigated in breast cell lines. Results: Annexin A3 (ANX A3) was found to be differentially expressed amongst different breast pathologies. The diagnostic value of serum ANX A3 was validated by ELISA in an independent serum set representing the three groups. Here, ANX A3 was significantly upregulated in the benign disease group sera compared with other groups (P< 0.0005). Moreover, ANX A3 distinguished the benign breast disease group with sensitivities and specificities between 80-95%. Paired breast tissue immunostaining confirmed that ANX A3 was abundantly expressed in benign and to a lesser extent malignant neoplastic epithelium, compared to normal breast tissue. Finally, we illustrated ANX A3 expression in cell culture lysates and conditioned media from neoplastic breast cell lines, and its role in neoplastic breast cell migration in vitro. Conclusions: This study confirms the potential role of ANX A3 as a breast cancer biomarker and biological regulator. The specific functional and diagnostic role of ANX A3 in breast neoplasia warrants further multi-centre clinical evaluation. No conflict of interest. http://dx.doi.org/10.1016/j.ejso.2014.08.219
226. Impact of body mass index on outcome in patients with ER positive and HER2 negative breast cancer in Japan T. Utsumi1, N. Kobayashi1, M. Hikichi1, K. Ushimado1 1 Fujita Health University, Department Of Breast Surgery, Toyoake, Japan Background: Many studies have shown that body mass index (BMI) is correlated with risk of recurrence in breast cancer in Western countries. The prevalence of obesity is relative low in Japan and there are few studies
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.
ABSTRACTS Size of the primary tumor (P ¼ 0.002), LVI (P < 0.001), perineural invasion (P ¼ 0.084+) were significant factors determining the SLN metastasis Conclusions: The status of the axillary lymph nodes is one of the most important prognostic factors in women with early stage breast cancer. Size of the primary tumor, LVI and perineural invasion were significant factors determining the SLN metastasis. We have found independent preoperative predictive factors in our local population for the presence of nodal metastases. This information can aid patient selection for SLNB and improve patient counselling. No conflict of interest.
S93 Results. 200 consecutive patients, mean age 61 (range 28-99), were studied. 112(56%) did not meet any criteria for screening/ intervention. 88 (44%) met criteria either for screening in 55, and or family history assessment in 33. 57/88 (64.8%) meeting criteria did not have a mammogram or risk assessment. The stage of breast cancer was significantly earlier in those falling within guidelines, with early stage in n¼114 (79.7%) and late in n¼29 (20.3%), compared to early in 63.2% and late in 36.8% of those failing to be screened appropriately (p¼0.01 c2 df1). Conclusion. This study identified the hazards of not been screened with resultant late diagnosis and negative prognostic implications. No conflict of interest.
http://dx.doi.org/10.1016/j.ejso.2014.08.216 http://dx.doi.org/10.1016/j.ejso.2014.08.218 223. Primary small cell carcinoma of the breast K. Park1, M.J. Jung2, S.I. Yang1 1 Kosin University College of Medicine, Department of Surgery, Busan, South Korea 2 Kosin University College of Medicine, Department of Pathology, Busan, South Korea Background: Primary SCC of the breast accounts for less than 1% of primary breast cancers. Due to the rarity of this type of tumor and the lack of a standard treatment, we report here a case study of primary SCC of the breast and discuss its clinicopathologic characteristics. Methods: A 58-year-old female patient presented with a painless mass in right breast for 2 months. An ultrasound scan revealed two solid and low heterogeneous echoes in the left breast: one was in the 3 o’clock position, 35 mm away from the nipple. A mass was poorly defined with irregular borders. She underwent modified radical mastectomy with axillary lymph node dissection. Microscopically, the mass (in the 3 o’clock position, 35 mm away from the nipple) was about 2.2 cm 1.8 cm 1.6 cm, which was diagnosed histologically small cell carcinoma with glandular differentiation. Immunohistochemically, tumor cells were negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) and histological examination also demonstrated 1 positive lymph node out of 25 axillary lymph nodes. The patient was scheduled to receive systemic chemotherapy with doxorubicin-cyclophosphamide followed by docetaxel (AC / T) every 3 weeks (60 mg/m2 doxorubicin, 600 mg/m2 cyclophosphamide and 75 mg/m2 docetaxel). Results: The patient is currently free of disease 50 months after operation with adjuvant chemotherapy. Conclusions: In this report, we describe a case of primary small cell carcinoma of the breast. No conflict of interest. http://dx.doi.org/10.1016/j.ejso.2014.08.217
224. Failure to engage in breast screening and risk assessment results in more advanced stage at diagnosis M. Sugrue1, A. Johnston1, S. Curran1 1 Letterkenny General Hospital, Breast Centre North West, Co Donegal, Ireland Introduction. Population based screening and family risk assessment for breast cancer while well established, has come under scrutiny recently. The concept of over-diagnosis is topical in recent cancer publications. This study assessed the impact of failure to screen or risk assess patients attending a designated breast cancer unit with a newly diagnosed breast cancer. Methods. A retrospective review was undertaken of 200 consecutive patients with breast cancer between January 2010 - September 2012 at Letterkenny Hospital. Appropriate screening was defined as biennial in those aged 50-66 and 40-49 with moderate / high family history risk (NICE criteria or IBIS criteria). Patient demographics, diagnosis date, stage (TNM) were documented. Patients with previous breast cancer were not included (n¼6).
225. Annexin A3 is a breast cancer marker secreted by neoplastic cell lines and is involved in cell migration B. Zeidan1, T. Jackson2, S. Larkin1, R. Cutress1, M. Ashton-Key1, G. Packham1, S. Garbis1, P. Townsend2 1 University of Southampton, Cancer Sciences, Southampton, United Kingdom 2 University of Manchester, Cancer Sciences, Manchester, United Kingdom Background: This study was designed to identify and functionally characterise potential breast cancer biomarkers in patients prior to intervention. Materials and methods: We used mass spectrometry (MS) to analyse serum samples representing 630 controls, 192 benign breast disease (BBD) and 219 invasive breast cancer (IDC) patients prior to intervention. Using liquid chromatography, free-flow electrophoresis (FFE), and immunoprecipitation isolation and purification techniques followed by the combined use of mass spectrometry (MS) tools with enzyme-linked immunosorbent assay (ELISA) validation we identified potential biomarkers. The diagnostic value of serum biomarkers were subsequently validated by ELISA in an independent serum set, as well as breast tissue from samples representing the three groups. The functional role of markers were also investigated in breast cell lines. Results: Annexin A3 (ANX A3) was found to be differentially expressed amongst different breast pathologies. The diagnostic value of serum ANX A3 was validated by ELISA in an independent serum set representing the three groups. Here, ANX A3 was significantly upregulated in the benign disease group sera compared with other groups (P< 0.0005). Moreover, ANX A3 distinguished the benign breast disease group with sensitivities and specificities between 80-95%. Paired breast tissue immunostaining confirmed that ANX A3 was abundantly expressed in benign and to a lesser extent malignant neoplastic epithelium, compared to normal breast tissue. Finally, we illustrated ANX A3 expression in cell culture lysates and conditioned media from neoplastic breast cell lines, and its role in neoplastic breast cell migration in vitro. Conclusions: This study confirms the potential role of ANX A3 as a breast cancer biomarker and biological regulator. The specific functional and diagnostic role of ANX A3 in breast neoplasia warrants further multi-centre clinical evaluation. No conflict of interest. http://dx.doi.org/10.1016/j.ejso.2014.08.219
226. Impact of body mass index on outcome in patients with ER positive and HER2 negative breast cancer in Japan T. Utsumi1, N. Kobayashi1, M. Hikichi1, K. Ushimado1 1 Fujita Health University, Department Of Breast Surgery, Toyoake, Japan Background: Many studies have shown that body mass index (BMI) is correlated with risk of recurrence in breast cancer in Western countries. The prevalence of obesity is relative low in Japan and there are few studies