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P134 The experience of sentinel lymph node biopsy in Chinese breast cancer patients with prior neo-adjuvant chemotherapy
Friday, 16 March 2007 predicting outcome following neoadjuvant endocrine therapy. The aim of this study was to determine which factors predicted for a course of specific survival after neoadjuvant treatment with aromatase inhibitors. Patients and Methods: 153 postmenopausal women with large operable or locally advanced estrogen receptor (ER) rich tumours (Allred score 5−8) were treated for at least 3 months with either letrozole n = 120, anastrozole n = 23 or exemestane n = 10. The mean patient age was 74.7 years. Tumour biopsies were taken prior to starting therapy and at 3 months. At 3 months patients either underwent surgery, with assessment of node status or continued on the same AI. Responding patients continued on the same AI following surgery for 3 years. Data on tumour size, T stage, node status, grade, ER level, Ki67 pre and post surgery and response were collected. Median follow up was 41 months. Overall 5 year survival was 63.1% with a 79.8% cause specific survival. Results: By 3 months 103/153 (67%) had responded with a >50% reduction in volume and only 4/153 (3%) had progressive disease. In the univariate analysis T stage (p = 0.03) node status at surgery (p = 0.005), Ki67 at diagnosis (p = 0.036), % reduction in Ki67 over 3 months (p = 0.027) and Ki67 at 3 months (p = 0.03) were significantly correlated with breast cancer specific survival. In the proportional hazards analysis the only significant variables were the number of positive nodes (p = 0.0007); % reduction in Ki67 (p = 0.003) and tumour grade (p = 0.038). Excluding variables not available at diagnosis the significant factors were baseline Ki67 (p = 0.02) and T stage (p = 0.02). Conclusion: Two thirds of post-menopausal women with ER rich large operable or locally advanced breast cancers respond to 3 months of neoadjuvant therapy with an AI. Node status at surgery and % reduction in Ki67 and tumour grades are the major factors predicting subsequent death from breast cancer in patients treated by neoadjuvant therapy with an aromatase inhibitor.
P133 HER2 and topoisomerase IIa: possible predictors of response to neoadjuvant chemotherapy for patients with breast cancer L. Zhu, Y.F. Li, W.G. Chen, J.R. He, Z.G. Zhu, H.W. Li. School of Medicine, Shanghai Jiao Tong University, Surgery, Shanghai, China Purpose: Surrogate markers may be used to assess response to neoadjuvant treatment. The association between HER2 overexpression and favorable response to specific therapy in breast cancer is controversial, and the mechanism unclear. The purpose of the study is to evaluate HER2 and topoisomerase IIa (TOPO IIa) as candidates for predicting the response to neoadjuvant chemotherapy in breast cancer patients. Methods: Between 1999 and 2006, eighty-nine breast cancer patients who had received neoadjuvant chemotherapy were studied. Regimens including either CEF (cyclophosphamide, epirubicin, 5-fluorouracil) or CMF (cyclophosphamide, methotrexate, 5-fluorouracil) were given more than three cycles to this group of patients. Protein expressions of HER2 and TOPO IIa were determined by immunohistochemistry (IHC). The primary endpoint was pathological and clinical response. Results: Of 89 primary breast cancer samples, 30 (33.7%) showed overexpression of either HER2 (23.6%) or TOPO IIa protein (10.1%), whereas in 8 tumors (9.0%) both proteins were found to be overexpressed. Thirtyfive patients (39.3%) had a clinical complete response, and 39 (43.8%) had a clinical partial response. Fifteen women (16.9%) had a pathological complete response, 21 (23.6%) had microscopic residual disease, and 53 (59.6%) had macroscopic residual disease. In CEF arm, HER2 overexpression was significantly associated with favorable response (P = 0.008). Co-expression of HER2 and TOPO IIa was significantly associated with favorable response in both groups of the patients (P = 0.034 and 0.021 respectively). Conclusions: Our study suggests that HER2 overexpression could be a predictor of response to anthracycline-based neoadjuvant regimens. The predictive value of HER2 would most likely be related to the concomitant expression of TOPO II in both CEF and CMF arms.
Poster Session II. Neo-adjuvant (pre-op) systemic therapy
S51
P134 The experience of sentinel lymph node biopsy in Chinese breast cancer patients with prior neo-adjuvant chemotherapy A. Kwong1,2 , D.T.K. Suen1 , T.T. Cheung1 . 1 University of Hong Kong, Li Ka Shing Faculty of Medicine, Department of Breast Surgery, Hong Kong, Hong Kong, 2 University of Stanford Medical School, Department of Surgery, California, USA Objective: Sentinel lymph node biopsy (SLNB) is well accepted as part of management of early breast cancer. As neo-adjuvant chemotherapy (NACT) is increasingly used in management of locally advanced breast cancer (LABC), breast conservative surgery has become a possibility even for patients who initially present with large tumours. However reports on the performance of sentinel lymph node biopsy (SLNB) following neo-adjuvant chemotherapy (NACT) have been conflicting. In addition, limited number of reports from Chinese breast cancer patients are available. This study aims to evaluate the results of SLNB after neo-adjuvant chemotherapy in Chinese breast cancer patients. Methods: A retrospective study was performed for breast cancer patients who had SLNB after prior neo-adjuvant chemotherapy. Adriamycin-based or taxane-based chemotherapy was given as neo-adjuvant treatment. A combination of radiopharmaceutical 99m Tc-albumin colloid and Patent Blue V dye was used to identify the sentinel lymph node (SLN). SLNB was followed by standard axillary dissection in all patients. Results: 365 patients received SLNB during the period of May 1999 to April 2006. A total of 78 patients with neo-adjuvant chemotherapy followed by SLNB were recruited. The SLN identification rate, false-negative rate and accuracy rate were 83.3%, 24.2% and 73.1% respectively. SLNs were identified in 11 (84.6%) of 13 patients with complete clinical response and no false-negative SLN was found. SLNs were found in 54 (83.1%) of 65 patients with partial or no clinical response and false-negative rate was 25%. In the 7 patients with complete pathological response, 6 (85.7%) had SLNs identified with no false-negative node. In the 71 patients with partial or no pathological response, 59 (83.1%) had SLN identified with a false-negative rate of 24.2%. Conclusion: The failed localization and false-negative rates of SLNB after neoadjuvant chemotherapy were unacceptably high in our cohort, concurrent with various published studies. Inaccuracy increases in patients with less than complete clinical or pathological tumor response.
P135 Primary systemic therapy of invasive lobular cancer: Is there a role for chemotherapy? A. Katz1 , E. Saad2 , P. Porter3 , L. Pusztai4 . 1 Centro Paulista de Oncologia ˜ Paulo, Brazil, 2 Dendrix, and Albert Einstein H, Medical Oncology, Sao ˜ Paulo, Brazil, 3 University of Washington, Pathology Department, Sao Seattle, USA, 4 MD Anderson Cancer Center, Breast Medical Oncology, Houston, USA Invasive lobular carcinoma (ILC) constitutes 10−15% of cases of invasive BC. In ongoing NCI-sponsored, randomized trials (RT) of early BC, His is not a stratification factor, despite the suggestion that ILC might have distinct clinical behavior and gene expression profile. Compared with invasive ductal carcinoma (IDC), ILC is more frequently of lower grade and positive for estrogen receptor (ER). ILC patients (PTS) frequently present with large tumors and with positive axillary lymph nodes, and are therefore routinely treated with adjuvant chemotherapy, according to several commonly accepted guidelines. Methods: We reviewed the literature to evaluate the role of His in Adj and NA therapy, by quantifying its impact on the pathologic response (pCR) rate to NA chemotherapy (CT), and on the results of adjuvant trials. We also compiled retrospective series analyzing pCR to NA CT according to His. Results: We retrieved 16 RT (8 phase III, 8 phase II) of NA therapy; None of the RT used His for stratification; 5 studies described His at randomization, but only 1 provided information on pCR rate to CT according to His (Dieras et al, 4.0% for ILC, 8.3% for IDC). Compiled results of 6 retrospective series which included nearly 3,000 PTS showed a pCR rate of 1.7% (6 of 354) in ILC PTS and of 11.6% (300 of 2584) in IDC PTS (P < 0.01). Of 39 phase III RT of Adj CT, only 4 described His in demography (9%, 9%, 10% and 12% of PTS were ILC), but none analyzed results according to His. In addition, 28/39 trials included ER negative PTS. Conclusions: We suggest that the role of CT in early ILC is not clear: The pCR rate is significantly lower in ILC PTS treated with NA CT. It is
P133 HER2 and topoisomerase IIa: possible predictors of response to neoadjuvant chemotherapy for patients with breast cancer L. Zhu, Y.F. Li, W.G. Chen, J.R. He, Z.G. Zhu, H.W. Li. School of Medicine, Shanghai Jiao Tong University, Surgery, Shanghai, China Purpose: Surrogate markers may be used to assess response to neoadjuvant treatment. The association between HER2 overexpression and favorable response to specific therapy in breast cancer is controversial, and the mechanism unclear. The purpose of the study is to evaluate HER2 and topoisomerase IIa (TOPO IIa) as candidates for predicting the response to neoadjuvant chemotherapy in breast cancer patients. Methods: Between 1999 and 2006, eighty-nine breast cancer patients who had received neoadjuvant chemotherapy were studied. Regimens including either CEF (cyclophosphamide, epirubicin, 5-fluorouracil) or CMF (cyclophosphamide, methotrexate, 5-fluorouracil) were given more than three cycles to this group of patients. Protein expressions of HER2 and TOPO IIa were determined by immunohistochemistry (IHC). The primary endpoint was pathological and clinical response. Results: Of 89 primary breast cancer samples, 30 (33.7%) showed overexpression of either HER2 (23.6%) or TOPO IIa protein (10.1%), whereas in 8 tumors (9.0%) both proteins were found to be overexpressed. Thirtyfive patients (39.3%) had a clinical complete response, and 39 (43.8%) had a clinical partial response. Fifteen women (16.9%) had a pathological complete response, 21 (23.6%) had microscopic residual disease, and 53 (59.6%) had macroscopic residual disease. In CEF arm, HER2 overexpression was significantly associated with favorable response (P = 0.008). Co-expression of HER2 and TOPO IIa was significantly associated with favorable response in both groups of the patients (P = 0.034 and 0.021 respectively). Conclusions: Our study suggests that HER2 overexpression could be a predictor of response to anthracycline-based neoadjuvant regimens. The predictive value of HER2 would most likely be related to the concomitant expression of TOPO II in both CEF and CMF arms.
Poster Session II. Neo-adjuvant (pre-op) systemic therapy
S51
P134 The experience of sentinel lymph node biopsy in Chinese breast cancer patients with prior neo-adjuvant chemotherapy A. Kwong1,2 , D.T.K. Suen1 , T.T. Cheung1 . 1 University of Hong Kong, Li Ka Shing Faculty of Medicine, Department of Breast Surgery, Hong Kong, Hong Kong, 2 University of Stanford Medical School, Department of Surgery, California, USA Objective: Sentinel lymph node biopsy (SLNB) is well accepted as part of management of early breast cancer. As neo-adjuvant chemotherapy (NACT) is increasingly used in management of locally advanced breast cancer (LABC), breast conservative surgery has become a possibility even for patients who initially present with large tumours. However reports on the performance of sentinel lymph node biopsy (SLNB) following neo-adjuvant chemotherapy (NACT) have been conflicting. In addition, limited number of reports from Chinese breast cancer patients are available. This study aims to evaluate the results of SLNB after neo-adjuvant chemotherapy in Chinese breast cancer patients. Methods: A retrospective study was performed for breast cancer patients who had SLNB after prior neo-adjuvant chemotherapy. Adriamycin-based or taxane-based chemotherapy was given as neo-adjuvant treatment. A combination of radiopharmaceutical 99m Tc-albumin colloid and Patent Blue V dye was used to identify the sentinel lymph node (SLN). SLNB was followed by standard axillary dissection in all patients. Results: 365 patients received SLNB during the period of May 1999 to April 2006. A total of 78 patients with neo-adjuvant chemotherapy followed by SLNB were recruited. The SLN identification rate, false-negative rate and accuracy rate were 83.3%, 24.2% and 73.1% respectively. SLNs were identified in 11 (84.6%) of 13 patients with complete clinical response and no false-negative SLN was found. SLNs were found in 54 (83.1%) of 65 patients with partial or no clinical response and false-negative rate was 25%. In the 7 patients with complete pathological response, 6 (85.7%) had SLNs identified with no false-negative node. In the 71 patients with partial or no pathological response, 59 (83.1%) had SLN identified with a false-negative rate of 24.2%. Conclusion: The failed localization and false-negative rates of SLNB after neoadjuvant chemotherapy were unacceptably high in our cohort, concurrent with various published studies. Inaccuracy increases in patients with less than complete clinical or pathological tumor response.
P135 Primary systemic therapy of invasive lobular cancer: Is there a role for chemotherapy? A. Katz1 , E. Saad2 , P. Porter3 , L. Pusztai4 . 1 Centro Paulista de Oncologia ˜ Paulo, Brazil, 2 Dendrix, and Albert Einstein H, Medical Oncology, Sao ˜ Paulo, Brazil, 3 University of Washington, Pathology Department, Sao Seattle, USA, 4 MD Anderson Cancer Center, Breast Medical Oncology, Houston, USA Invasive lobular carcinoma (ILC) constitutes 10−15% of cases of invasive BC. In ongoing NCI-sponsored, randomized trials (RT) of early BC, His is not a stratification factor, despite the suggestion that ILC might have distinct clinical behavior and gene expression profile. Compared with invasive ductal carcinoma (IDC), ILC is more frequently of lower grade and positive for estrogen receptor (ER). ILC patients (PTS) frequently present with large tumors and with positive axillary lymph nodes, and are therefore routinely treated with adjuvant chemotherapy, according to several commonly accepted guidelines. Methods: We reviewed the literature to evaluate the role of His in Adj and NA therapy, by quantifying its impact on the pathologic response (pCR) rate to NA chemotherapy (CT), and on the results of adjuvant trials. We also compiled retrospective series analyzing pCR to NA CT according to His. Results: We retrieved 16 RT (8 phase III, 8 phase II) of NA therapy; None of the RT used His for stratification; 5 studies described His at randomization, but only 1 provided information on pCR rate to CT according to His (Dieras et al, 4.0% for ILC, 8.3% for IDC). Compiled results of 6 retrospective series which included nearly 3,000 PTS showed a pCR rate of 1.7% (6 of 354) in ILC PTS and of 11.6% (300 of 2584) in IDC PTS (P < 0.01). Of 39 phase III RT of Adj CT, only 4 described His in demography (9%, 9%, 10% and 12% of PTS were ILC), but none analyzed results according to His. In addition, 28/39 trials included ER negative PTS. Conclusions: We suggest that the role of CT in early ILC is not clear: The pCR rate is significantly lower in ILC PTS treated with NA CT. It is