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P210 Discordance of prognostic risk between histopathology and gene signature in Japanese early breast cancer
Thursday, 17 March 2011 compared the risk category between well-known prognostic tools and the 21-gene signature (Oncotype DX® , ODX), and explored whether the conventional pathological factors could substitute for the Recurrence Score (RS), as measured by ODX. Methods: This study was conducted from October 2007 to October 2010. ODX was provided to 142 women diagnosed with hormone receptorpositive invasive breast cancer to assist with treatment decisions. The risk categories between ODX, the St.Gallen 2007 Guidelines (SG), and Adjuvant! Online (AOL) were compared. Next, the relationship between the RS and pathological factors (tumor size (T), lymph node metastasis (N), nuclear atypia (NA), mitotic counts (MC), nuclear grade (NG), lymphatic and vascular invasion (LI, VI), estrogen and progesterone receptor (ER, PgR), HER2 and Ki-67 were analyzed. Ki-67 was automatically counted by an Ariol-SL50 instrument. Spearman rank correlation coefficients and associated 95% confidence intervals were calculated. Results: In 142 women, the ODX revealed 68 low (48%), 55 intermediate (39%), and 19 high risk patients (13%). SG revealed 14 low (10%), 123 intermediate (87%), and 5 high risk patients (3%). In the intermediate group indicated by SG, 56 cases (45%) were low risk by ODX. AOL found 49 low (35%), and 93 high risk patients (65%). The AOL 10-year recurrence risk was poorly correlated with RS (rs = 0.26).There were moderate positive correlations between the RS and NG (rs =0.43), MC (rs =0.40) and Ki67 (rs =0.43), and a moderate negative correlation with PgR (rs = −0.55). Correlations with T, N, NA, LI, VI, ER and HER2 were smaller (rs from −0.32 to 0.23). Conclusion: This report demonstrated the inconsistency between ODX and conventional tools. The RS is moderately correlated with NG, PgR, MC and Ki-67, but none of these conventional pathological factors were equivalent to the RS. Disclosure of Interest: None Declared
P210
Discordance of prognostic risk between histopathology and gene signature in Japanese early breast cancer
M. Saito1 , H. Shimizu1 , H. Miura1 , K. Nakai1 , T. Kosaka1 , K. Senuma1 , I. Abe1 , A. Arakawa2 , F. Kasumi1 . 1 Breast Oncology, 2 Pathology, Juntendo University, Tokyo, Japan Goals: Recently, the prognostic value of gene signatures for breast cancer with intermediate risk has been recognized. To evaluate the effects of 70 gene signature (MMP) for Japanese patients, prospective observational study has been performed. This is the report of interim analysis of the study. Methods: Fresh tumor samples from 50 node negative early breast cancer patients without undergoing neoadjuvant chemotherapy were collected during surgery for MMP and histological examination in our hospital. To evaluate the role of MMP as an independent prognostic factor, discordance of prognostic risk between histopathology and MMP was investigated. Results: Analysis of 25 cases has been completed so far. 5 out of 25 samples were too small in size to be analyzed for MMP. Among 20 cases, 8 cases were categorized into high risk and 12 cases were low risk by MMP. Among those high risk cases, 2 out of 8 cases were low risk by St.Gallen 2007 risk category (St.Gallen). Among low risk, 7 out of 12 cases were intermediate risk by St.Gallen. Conclusion: The rate of discordant cases between St.Gallen and MMP was 45% in our small pilot study. This result indicates the potential value of MMP is extremely high to avoid adjuvant chemotherapy for early breast cancer. However, the requirement of enough sample size (larger than 15 mm in diameter) for analysis is indicated to be one of the issues for MMP to be utilized for all the early breast cancers. Disclosure of Interest: None Declared
P211
High SUV max of 18f FDG-PET/CT is significantly associated with poor outcome in operable breast cancer
M. Ohara1 , H. Shigematsu1 , S. Ozaki1 , A. Emi1 , M. Okada1 . 1 Department of breast surgery, Hiroshima University Hospital, Hiroshima, Japan Goals: The aim of this study was to evaluate the prognostic value of a maximum standardized uptake value (SUV max) 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT) for primary tumor in operable breast cancer patients.
Poster Session I. Predictive and prognostic factors
S47
Methods: We retrospectively examined consecutive 320 patients with operable invasive breast cancer who had received 18 F-FDG PET/CT for staging of breast cancer from 2005 to 2010. The association between SUVmax and clinicopathological factors, and the effect of SUVmax on prognosis were evaluated. Results: Median follow-up was 28.0 months.Mean ofSUVmax was 3.60 (0.8–22.5). High SUVmax was significantly correlated with larger clinical tumor size (P < 0.001), higher nuclear grade (P < 0.001), negative hormone receptor status (P = 0.001), lymphovascular invasion (P = 0.022), andpresence of lymph node metastasis (P = 0.004). Receiver operating characteristics (ROC) curve analysis demonstrated that cutoff value of SUVmax to predict cancer recurrences was 4.25 in IDC. 3-Year DFS was 99.6% for patients with SUVmax 4.25 and 88.4% for patients with SUVmax >4.25 (P < 0.001). Based on the multivariate Cox analysis in patients with IDC, highSUVmax (P = 0.008) and negative hormone receptor status (P = 0.046) were significantly associated with poor prognosis. As exploratory analysis, we evaluated prognostic impact of SUVmax individe patients with triple negative tumors. ROC curves identified an optimal SUVmax cut-off value of 7.3 for predicting the recurrence of triple negative subtype.In multivariate analysis, high SUVmax (>7.3) was associated with poor prognosis and was the only significant independent prognostic factor in triple negative subtype (P = 0.020). Conclusion: SUVmax in the primary tumor was correlated with poor prognostic factors and early relapse in patients withoperable breast cancer. SUVmax was also significant poor prognostic factor intriple negative subtype. Disclosure of Interest: None Declared
P212
High VEGF-C/VEGF-D mRNA expression ratio in breast cancer may correlate with lymph node metastasis and recurrence
Y. Koyama1 , E. Sakata1 , C. Toshikawa1 , M. Hasegawa1 , N. Manba1 , M. Ikarashi1 , K. Hatakeyama1 . 1 Division of Digestive & General Surgery, Niigata University Graduate School of Medical & De, Niigata, Japan Goals: Both VEGF-C and VEGF-D, as ligands for VEGFR-3, are capable of stimulating lymphangiogenesis and at least VEGF-C can enhance lymphatic metastasis. We previously reported the correlation between VEGF-C/VEGF-D ratio and lymph node metastasis (Koyama, et al. Clin Breast Cancer 4:354−60, 2003).The aim of the present study was to explore the relationship between VEGF-C/VEGF-D mRNA expression and recurrence/survival in breast cancer. Methods: Human breast tissues were obtained from 33 breast cancer patients. Total RNAs were isolated from 34 surgical specimens of breast cancer tissue and 7 normal breast tissues. The relative mRNA abundance of VEGF-C and VEGF-D was measured by real-time reverse transcriptionPCR analysis based on TaqMan method. VEGF-C/VEGF-D mRNA ratio (VEGF-C/D ratio) was compared between cancer and normal tissues, and between recurrence positive and negative group. In the present study, by using the value of mean +SD of VEGF-C/D ratio in the patients without recurrence as cut-off line, we divided patients into two groups; VEGF-C/D ratio high group and low group. Bothdisease free survival (DFS) and overall survival (OS) were compared between VEGF-C/D ratio high and low group. Statistical analyses were performed using Mann–Whitney’s U test, Chi-square test and Log-rank test, and the statistical significance was defined as p < 0.05. Results: VEGF-C/D ratio was significantly increased in breast cancer tissues compared with normal breast tissue (p < 0.05). There was no significant difference in VEGF-C or VEGF-D mRNA expression showed between recurrence positive vs negative group. However, VEGF-C/D ratio was significantly high in the recurrence positive patients (p < 0.05), and was also high in the node metastasis positive patients (p < 0.05).Although there was no significant difference in OS between VEGF-C/D ratio high vs low group, however, DFS was significantly low in VEGF-C/D ratio high group (p < 0.05). Conclusion: Our results showed that the increased VEGF-C/VEGF-D mRNA expression ratio in breast cancer has an association with lymph node metastasis and recurrence. And also, VEGF-C/VEGF-D mRNA expression ratio may become a prognostic factor in breast cancer. Disclosure of Interest: None Declared
P210
Discordance of prognostic risk between histopathology and gene signature in Japanese early breast cancer
M. Saito1 , H. Shimizu1 , H. Miura1 , K. Nakai1 , T. Kosaka1 , K. Senuma1 , I. Abe1 , A. Arakawa2 , F. Kasumi1 . 1 Breast Oncology, 2 Pathology, Juntendo University, Tokyo, Japan Goals: Recently, the prognostic value of gene signatures for breast cancer with intermediate risk has been recognized. To evaluate the effects of 70 gene signature (MMP) for Japanese patients, prospective observational study has been performed. This is the report of interim analysis of the study. Methods: Fresh tumor samples from 50 node negative early breast cancer patients without undergoing neoadjuvant chemotherapy were collected during surgery for MMP and histological examination in our hospital. To evaluate the role of MMP as an independent prognostic factor, discordance of prognostic risk between histopathology and MMP was investigated. Results: Analysis of 25 cases has been completed so far. 5 out of 25 samples were too small in size to be analyzed for MMP. Among 20 cases, 8 cases were categorized into high risk and 12 cases were low risk by MMP. Among those high risk cases, 2 out of 8 cases were low risk by St.Gallen 2007 risk category (St.Gallen). Among low risk, 7 out of 12 cases were intermediate risk by St.Gallen. Conclusion: The rate of discordant cases between St.Gallen and MMP was 45% in our small pilot study. This result indicates the potential value of MMP is extremely high to avoid adjuvant chemotherapy for early breast cancer. However, the requirement of enough sample size (larger than 15 mm in diameter) for analysis is indicated to be one of the issues for MMP to be utilized for all the early breast cancers. Disclosure of Interest: None Declared
P211
High SUV max of 18f FDG-PET/CT is significantly associated with poor outcome in operable breast cancer
M. Ohara1 , H. Shigematsu1 , S. Ozaki1 , A. Emi1 , M. Okada1 . 1 Department of breast surgery, Hiroshima University Hospital, Hiroshima, Japan Goals: The aim of this study was to evaluate the prognostic value of a maximum standardized uptake value (SUV max) 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT) for primary tumor in operable breast cancer patients.
Poster Session I. Predictive and prognostic factors
S47
Methods: We retrospectively examined consecutive 320 patients with operable invasive breast cancer who had received 18 F-FDG PET/CT for staging of breast cancer from 2005 to 2010. The association between SUVmax and clinicopathological factors, and the effect of SUVmax on prognosis were evaluated. Results: Median follow-up was 28.0 months.Mean ofSUVmax was 3.60 (0.8–22.5). High SUVmax was significantly correlated with larger clinical tumor size (P < 0.001), higher nuclear grade (P < 0.001), negative hormone receptor status (P = 0.001), lymphovascular invasion (P = 0.022), andpresence of lymph node metastasis (P = 0.004). Receiver operating characteristics (ROC) curve analysis demonstrated that cutoff value of SUVmax to predict cancer recurrences was 4.25 in IDC. 3-Year DFS was 99.6% for patients with SUVmax 4.25 and 88.4% for patients with SUVmax >4.25 (P < 0.001). Based on the multivariate Cox analysis in patients with IDC, highSUVmax (P = 0.008) and negative hormone receptor status (P = 0.046) were significantly associated with poor prognosis. As exploratory analysis, we evaluated prognostic impact of SUVmax individe patients with triple negative tumors. ROC curves identified an optimal SUVmax cut-off value of 7.3 for predicting the recurrence of triple negative subtype.In multivariate analysis, high SUVmax (>7.3) was associated with poor prognosis and was the only significant independent prognostic factor in triple negative subtype (P = 0.020). Conclusion: SUVmax in the primary tumor was correlated with poor prognostic factors and early relapse in patients withoperable breast cancer. SUVmax was also significant poor prognostic factor intriple negative subtype. Disclosure of Interest: None Declared
P212
High VEGF-C/VEGF-D mRNA expression ratio in breast cancer may correlate with lymph node metastasis and recurrence
Y. Koyama1 , E. Sakata1 , C. Toshikawa1 , M. Hasegawa1 , N. Manba1 , M. Ikarashi1 , K. Hatakeyama1 . 1 Division of Digestive & General Surgery, Niigata University Graduate School of Medical & De, Niigata, Japan Goals: Both VEGF-C and VEGF-D, as ligands for VEGFR-3, are capable of stimulating lymphangiogenesis and at least VEGF-C can enhance lymphatic metastasis. We previously reported the correlation between VEGF-C/VEGF-D ratio and lymph node metastasis (Koyama, et al. Clin Breast Cancer 4:354−60, 2003).The aim of the present study was to explore the relationship between VEGF-C/VEGF-D mRNA expression and recurrence/survival in breast cancer. Methods: Human breast tissues were obtained from 33 breast cancer patients. Total RNAs were isolated from 34 surgical specimens of breast cancer tissue and 7 normal breast tissues. The relative mRNA abundance of VEGF-C and VEGF-D was measured by real-time reverse transcriptionPCR analysis based on TaqMan method. VEGF-C/VEGF-D mRNA ratio (VEGF-C/D ratio) was compared between cancer and normal tissues, and between recurrence positive and negative group. In the present study, by using the value of mean +SD of VEGF-C/D ratio in the patients without recurrence as cut-off line, we divided patients into two groups; VEGF-C/D ratio high group and low group. Bothdisease free survival (DFS) and overall survival (OS) were compared between VEGF-C/D ratio high and low group. Statistical analyses were performed using Mann–Whitney’s U test, Chi-square test and Log-rank test, and the statistical significance was defined as p < 0.05. Results: VEGF-C/D ratio was significantly increased in breast cancer tissues compared with normal breast tissue (p < 0.05). There was no significant difference in VEGF-C or VEGF-D mRNA expression showed between recurrence positive vs negative group. However, VEGF-C/D ratio was significantly high in the recurrence positive patients (p < 0.05), and was also high in the node metastasis positive patients (p < 0.05).Although there was no significant difference in OS between VEGF-C/D ratio high vs low group, however, DFS was significantly low in VEGF-C/D ratio high group (p < 0.05). Conclusion: Our results showed that the increased VEGF-C/VEGF-D mRNA expression ratio in breast cancer has an association with lymph node metastasis and recurrence. And also, VEGF-C/VEGF-D mRNA expression ratio may become a prognostic factor in breast cancer. Disclosure of Interest: None Declared