P47 Breast conservation treatment in women with locallyadvanced breast cancer

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Poster Session I. Surgery/DCIS

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NNBC-3 Europe: A prospective clinical trial on risk estimation and optimization of adjuvant chemotherapy in node-negative breast cancer patients

F. Herbst 1, N. Harbeck 2, K. Gauger 2 , N. Gaskill 1, F. Sweep 3, C. Meisner 4, M. Schmitt 2, F. Jaenicke 1, C. Thomssen 5 . i Universityhospital

Hamburg-Eppendorf, Clinic of Gynecology, Hamburg, Germany; 2 Technical University Munich, Clinic of Gynecology, Munich, Germany; 3 University Hospital Nijmegen, Experimental and Chemical Endocrinology, Nijmegen, Netherlands; 4 University Tuebingen, Medical Data Institute, Tuebingen, Germany; 5 Universityhospital Halle, Clinic of Gynecology, Halle, Germany

Background: Recent results demonstrated strong evidence for the routine use of the invasion markers urokinase-type plasminogen activator (uPA) and its inhibitor PAl-1 as prognostic factors in node-negative breast cancer. Lowrisk patients have an excellent 5-year overall survival (>95%) even without any adjuvant therapy. In contrast to risk estimation by St.Gallen criteria, the use of these invasion markers have shown to spare adjuvant chemotherapy for a substantial part of all node-negative breast cancer patients. In addition, patients with high uPA/PAI-1 seem to have enhanced benefit from adjuvant chemotherapy. The NNBC-3 Europe trial seeks to answer two questions: 1) Is risk assessment by invasion markers uPA/PAI-1 superior to that by clinico-pathological factors with regard to identification of low-risk patients? 2) Is adjuvant chemotherapy using an anthracycline-taxane containing sequence (FEC-Docetaxel) superior to standard FEC in high-risk patients? Methods: In the NNBC-3 Europe trial, participating centres opt to either perform risk estimation by traditional clinico-pathological factors or by invasion markers uPA/PAI-I. Low-risk patients will then be observed without adjuvant chemotherapy. High-risk patients are randomised to adjuvant chemotherapy (FEC-100 *6 versus FEC-100 *3 followed by Docetaxel-100 *3). All patients with steroid hormone receptor positive tumors receive adequate endocrine therapy. Results: Of the first 171 patients (16 centers) in the tumor-biological arm, 14 (8%) had grade 1 tumors, and 63(37%) had grade 3 tumors. Among grade 2 tumors, 55% (n=94), 38(40%) had low levels of uPA (med. 1,0ng/mg protein) and PAl-1 (med. 8,2ng/mg); 56 (60%) patients presented with elevated values: uPA (med. 3,2ng/mg) and PAl-1 (med. 21,3ng/mg). Grade 3 tumors showed uPA at 2,7ng/mg and PAl-1 at 20,5ng/mg (med.). Overall, 30% of patients were allocated to the low-risk group, with no adjuvant chemotherapy. Conclusion: Conducting an adjuvant chemotherapy trial based on uPA/PAI-1 determination is feasible in a multicentre setting. Applying the invasion markers uPA/PAI-1 for risk assessment, in the first study patients, almost 52 were assigned to the low-risk group. Thus, in this early phase of the study, patient distribution shows to be in line with the expected distribution. The study is planned to recruit 5700 patients. This study is performed in association with the EORTC Receptor and Biomarker Group and the German AGO Breast Group.

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Impact of lymphoid infiltration of tumor on survival of young patients with breast cancer

N. Chobanyan 1, A. Gevorgyan 2 . 1National Institute of Health, Oncology,

Yerevan, Armenia; 2 National Institute of Health, Oncology, Yerevan, Armenia

Introduction: Survival of young patients with breast cancer is poor. Although, research shows negative influence of a significant number of pathological factors on survival of breast cancer patients, there is no clear impact of lymphoid infiltration of tumor on survival of patients with premenopausal cancer, particularly patients of young age. The aim of this study is to determine the impact of lymphoid infiltration of tumor on survival of young patients compared with middle age group. Material and method: Study involves 2 groups of patients with stages I1-111of premenopausal breast cancer. 375 patients were young age (20-35 years old), and 380 - middle age (36-45 years old). Lymphoid infiltration of tumor was analyzed on surgical specimens after mastectomy. 5-10, and 15year survival was established by "life table" method. Comparative analysis of 5- 10-, and 15 year survival done under influence of presence or absence of lymphoid infiltration of tumor in young and middle age patients. Results: Within each age group we did not observe influence of presence or absence of lymphoid infiltration of tumor on survival rates. Comparative analysis of survival rates of young and middle age patients showed statistically significant decrease of survival rate in the young patients with presence of lymphoid infiltration of tumor: 5 -year survival rate was 62,2+4,8% and 76,8+2,3%, respectively (p<0,05). 10 and 15- year survival rate was the same within each age group, but statistically significantly low in young patients compared with middle aged group (53,4+5,5%, and 65,2+3,1%, respectively) (p<0,05). Conclusion: Lymphoid infiltration of tumor showed statistically significant negative influence on survival of young patients with breast cancer compared

Thursday, 27 January 2005 with middle age group. Differences in survival rate of two age groups within premenopausal breast cancer may be reflection of the existence of basic differences of immune-endocrine relationships in patients young and middle age groups.

THURSDAY, 27 JANUARY 2005

Surgery/DCIS

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Therapeutic Results of Breast Conserving Surgery

M. Iwamoto 1, Y. Tatsumi 1, T. Harada 1, R. Yoshinaka 1, H. Nishimura 1, K. Sumiyoshi 1, S. Lee 1, i2 Kobayashi 1, i2 Nohara 1, N. Tanigawa 1. 1 Osaka

Medical College, Department of General and Gastroenterological Surg, Osaka, Japan

Introduction: We have performed breast conserving surgery since 1989. This paper reports the examination of the results of the treatment. Materials and methods: A total of 238 patients who received the breast conserving surgery until 2004 were included. In principle, quadrantectomy + axillary dissection was performed until 1998 and wide excision + axillary dissection was performed from 1998 on. All the patients received radiotherapy (50 Gy; a boost irradiation of 10 Gy was added for those who had no sufficient safety margin at the cut end). In principle, the tumor was excised with a margin of 2cm. Sentinel lymph node biopsy was introduced in 2001 to omit unnecessary dissection. Postoperative chemotherapy with CAF or CMF has been performed for those positive for lymph node metastasis. Tamoxifen has been administered for those positive for ER. Results: The age of the patients ranged from 23 to 94 years, with a mean age of 54.4 years. The tumor diameter ranged from 0 to 4.5 cm (mean: 1.8cm). For histological type, the patients were classified into 207 with invasive ductal carcinoma, 13 with intraductal carcinoma, and 18 with other types of carcinoma. For lymph node metastasis, they were classified into 186 at pN0, 35 at pN1, and 17 at pN2. For clinical staging, they were classified into 4 in Stage 0, 112 in Stage I, 115 in Stage II, and 7 in Stage II1. There was no safety margin at the cut end in six patients. Breast cancer recurred in 8 patients (3.4%), and recurrence sites included bone in 3 patients, lung in 2, liver in 1, and local site of the cancer in 2. The relapse-free rate of the patients was 96.6%, and overall survival rate 98.3% at the median follow up period of 4 years. Conclusions: The present examination showed that the breast conserving surgery provided satisfactory results when the tumor was excised with a sufficient safety margin and adjuvant chemotherapy was combined with radiotherapy.

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Breast conservation treatment in women with locally advanced breast cancer

V. Parmar 1, R.A. Badwe 1, R. Sarin 2, R. Jalali 2, R. Chinoy 3, R. Nair 4, S. Gupta 4, R. Hawaldar 5, M. Thakur 6, K.A. Dinshaw 2. i Tara Memorial

Hospital Surgical Oncology, MumbaL India; 2 Tata Memorial Hospital, Radiation Oncology, MumbaL India; 3 Tata Memorial Hospital, Pathology, Mumbai, India; 4 Tata Memorial Hospital, Medical Oncology, Mumbai, India; 5 Tata Memorial Hospital, Clinical Research Secretariat, Mumbai, India; 8 Tata Memorial Hospital Radiology, Mumbai, India

Introduction: Adequate randomized evidence is available to support breast conservation therapy (BCT) in operable breast cancer. BCT is also feasible in locally advanced breast cancer (LABC) after down-sizing with neo-adjuvant chemotherapy. However, there is inadequate data to support the safety of conservative surgery in locally advanced cancers. Material and Methods: We have critically analyzed the data in 744 women with LABC at first presentation, registered between January 1998 and December 2002 at Tata Memorial Hospital, Mumbai, India. All women were uniformly treated with a multimodality regimen comprising of neoadjuvant chemotherapy followed by surgery (modified radical mastectomy or breast conservation surgery), radiotherapy and hormone therapy (in receptor positive tumors). Results: 71% women responded to neoadjuvant chemotherapy (22% CR and 50% PR), and breast conservation was technically feasible and performed in 28% cases. Margins were reported positive after conservation in 8.5% with gross presence of tumor at the resection margins in 2.3% requiring a revision surgery or mastectomy. The local relapse rates after conservative surgery was 8.3% Vs 11.5% after mastectomy (p=NS). The disease-free survival at 3 years after conservation was 68% compared to 50% following mas-

Thursday, 27 January 2005 tectomy (p<0.0001). The local disease-free survival at 3 years was in favor of conservation (85% Vs 76%, p=0.03). The DFS at 5 years after conservation surgery Vs mastectomy was 60% Vs 30% (p<0.0001). The predictive factors for response to chemotherapy and prognostic factors for recurrence have been analyzed and will be presented at the meeting. Conclusion: Breast conservation therapy is technically feasible and safe in women with locally advanced breast cancer after sufficient down-staging with neo-adjuvant chemotherapy.

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Surgical Treatment of Early Breast Cancer - Moving Towards Breast Conservation and Immediate Breast Reconstruction

E.Y. Tan ~, M.Y.P. Chan, B.K. Ang, B.K. Tan 2 . 1 Tan Tock Seng Hospital,

Department of General Surgery, Singapore, Singapore; 2 Singapore General Hospital, Department of Plastic Surge~ Singapore, Singapore Total mastectomy has become less common in the treatment of early breast cancer (EBC). This has resulted largely from reports of the safety of breast conservation surgery (BCS) and from efforts to reduce the psychological impact of mastectomy. A retrospective review of 457 patients diagnosed with EBC in our department from January 2000 to December 2003 showed a significant trend towards BCS and immediate breast reconstruction following mastectomy (p <0.001). In 2000, 72.6% of those with EBC underwent total mastectomy, while by 2003, 71.4% opted for either BCS or immediate reconstruction. There has been no significant change in the age, ethnic group, tumour size or stage over the past 4 years. This trend towards BCS and reconstruction therefore reflects a change in the local mindset. As local women become more well-educated, they have become more concerned with their body image, and many no longer believe that total mastectomy removes the cancer more completely. Patients who undergo total mastectomy are significantly older than those who undergo BCS or reconstruction (p=0.001). There was no significant difference in ethnic group, martial status, parity, hormonal therapy use, family history or a personal history of breast cancer. Apart from tumour size (those with larger tumours tend to undergo mastectomy), tumour histology, grade, the presence of lymphovascular invasion and hormonal receptor status did not differ between the 2 groups. 33 patients (7.2%) underwent skin-sparing mastectomy followed by immediate breast reconstruction. These patients were younger and had fewer co-morbidities. 1 patient developed a stroke post-operatively. Partial flap necrosis occurred in 1 patient, while minor wound complications occurred in 7 others. Locoregional recurrences occurred in 9 patients during the follow-up period of 28.38 ± 12.85 months, 2 of whom were also found to have bone metastasis. Recurrence was not influenced by the type of surgery (p=0.709). 37 patients (17.4%) required repeat surgery following BCS due to margin involvement. 17 underwent re-excision of margins while 20 underwent total mastectomy (with immediate reconstruction in 7 patients). In conclusion, breast conservation surgery has now replaced total mastectomy as the standard of care for women with early breast cancer in our department. Selected patients are increasingly being offered the option of immediate breast reconstruction following skin-sparing mastectomy.

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Predictors of recurrence after breast conservation treatment in 1668 women

V. Parmar 1, R.A. Badwe 1, R. Hawaldar 2, R. Chinoy 3, R. Sarin 4, R. Jalali 4, R. Nair 5, S. Gupta 5, M. Thakur 6, K.A. Dinshaw 4. 1 Tata Memorial Hospital

Surgical Oncology, Mumbai, India; 2 Tata Memorial Hospital, Clinical Research Secretariat, Mumbai, India; 3 Tata Memorial Hospital Pathology, Mumbai, India; 4 Tata Memorial Hospital, Radiation Oncology, Mumbai, India; 5 Tata Memorial Hospital, Medical Oncology, MumbaL India; 6 Tata Memorial Hospital, Radiology, Mumbai, India

Introduction: Breast conservation treatment (BCT) is fast becoming the standard of care in operable breast cancer and, in consequence, is also being offered for locally advanced breast cancer (LABC) after down-sizing with neo-adjuvant chemotherapy. Randomized evidence is currently available in favor of BCT in operable breast cancer. No such evidence is available for post-chemotherapy breast conservation in LABC. We have critically analyzed our data from Tata Memorial hospital in 1668 women who underwent BCT during 1997-2003. Method: Women with both operable and locally advanced breast cancer were included in the analysis. In operable breast cancer, breast conservation is offered to all eligible women; in women with locally advanced breast cancer, breast conservation is offered if feasible after neo-adjuvant chemotherapy. Various patient and tumor variables were analyzed. Predictors of positive margin status were tested by chi-square test for univariate analysis, and by logistic regression analysis for multivariate analysis. Univariate and multivariate analysis of potential prognostic factors for local recurrence and

Poster Session I. Surgery/DCIS

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distant recurrence were performed using Kaplan-Meier survival analysis and Cox regression models for the whole group. Results: Predictors of positive margin after excision of primary tumor on univariate analysis were presence of extensive intraductal carcinoma (EIC) (p<0.001), positive nodal status (p<0.001), lymphovascular emboli (LVE) (p=0.001), and age<40 years (p=0.027). On multivariate analysis only EIC and positive nodal status remained as strong predictors of positive cut margin (p=<0.001 and p=0.002 respectively). Positive nodal status was also a significant predictor for local recurrence (p=0.001) and presence of LVE had a significant impact on distant metastases with a p value of <0.001. At a median follow up of 26.5 months, the local recurrence after BCT in OBC was 3.7% and 8.7% in locally advanced cancers (p=0.0001). Conclusion: Breast conservation is a feasible option in both operable and locally advanced breast cancer and should be offered to all women where feasible. Long term results of post-chemotherapy BCT are still awaited.

[P50~ Ten year experience with needle-localized open breast biopsy for non-palpable breast lesions: BIRADS classification and histopathologic correlation R. Cericatto 1, F. Bittelbrunn 2, C. Menke 1, J. Biaz~s 1, N. Xavier 1, J. Cavalheiro 1, A. Bittelbrunn 1, A. Furtado 2 . 1Hospital de Clfnicas de Porto

Alegre, Breast Service, Porto Alegre - RS, Brazil; 2 Hospital de Clfnicas de Porto Alegre, Radiology Service, Porto Alegre - RS, Brazil. Aim: With the increasing use of screening mammography, non-palpable breast lesions have become an important issue. Needle-localized open breast biopsy (NLBB) is the gold standard procedure to evaluate these lesions. The aim of this study was to report our ten-year experience with this technique and to correlate the Breast Imaging Reporting and Data System (BIRADS) with pathologic diagnosis. Patients and Methods: During the period of 1995 to 2004, 586 NLBB were performed in the Hospital de Clinicas de Porto Alegre, Brazil. These lesions have been classified according to BIRADS since 1998. Previous cases were retrospectively categorized by the radiologist team, without knowing the histologic outcome. Positive predictive value (PPV) for malignancy of each category was calculated. Results: The mean age of patients was 53 years (range 23-82 years). The overall PPV for malignancy of the sample was 0.32 (188/586 cases). The PPV increased with the level of suspicion: 0.05 for BIRADS 3 (8/155 cases), 0.29 for BIRADS 4 (99/339 cases) and 0.88 for BIRADS 5 (81/92 cases). Category 3 lesions represented 26.5% of the biopsies; category 4, 57.9%; and category 5, 15.7%. Fibrocystic changes (47.6%) were the most common histologic diagnosis of benign biopsies followed by fibroadenomas (19.8%). Ductal carcinoma in situ (DCIS) (47.8%) and infiltrative ductal carcinoma (43.1%) were the most common malignant reports. Microcalcifications (63.7%) and mass (37.2%) were the main lesions investigated, followed by asymmetrical density and parenchymal distortion. 94% of the DCIS were represented mammographically as suspected microcalcifications. Pleomorphic, clustered and ductal pattern calcifications presented with a superior PPV (0.55) when compared with non ductal distribution (PPV 0.25). Spiculated masses were associated with cancer in 88% cases. There was a 50% reduction in BIRADS 3 lesions submitted to NLBB when compared the periods of 1995-2000 (33.8% cases) and 2001-2004 (16.4% cases), probably because of increased use of less invasive techniques (stereotactic and ultrasound core biopsy) and conservative management, without an impact on false negative diagnosis. Conclusion: Our data validate the utility of BIRADS classification in predicting risk of malignancy and are a useful parameter to audit results of less invasive procedures that have been widely used in non-palpable breast evaluation.

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Axillary lymph node ratio and total number of removed lymph nodes

H. Lass, M. Brunbauer, S. Wildhofen, O. Merl, A. Tammaa, H. Salzer.

Wilhelminenspital der Stadt Wien, Abteilung f(Jr Gyn~kologie und Geburtshilfe, Vienna, Austria

Introduction: Axillary lymph node dissection (ALND), which is crucial for accurate staging, provides excellent regional tumour control and has remained an integral part of breast cancer management for more than a century. However the extent of ALND varies even the recommendations of nodes that should be removed is ten. The aim of this study was to evalute the ratio of removed lymph nodes and metastatic lymph nodes. Material and methods: 161 patients with breast-cancer were included. 117 patients underwent breast-conserving surgery and 44 modified radical mastectomy. All patients underwent ALND(level I-II and optional III) and the material was histological examined. Thereby it could be seen that 61 patients had lymph-node metastases, 100 had no metastasis. For each ALND the