Friday, 28 January 2005 Poster Session II. Neoadjuvant (Pre-op.) Therapy~Advanced Disease $43

48 months only 7 patients (4,2%) suffered a local relapse. 3 of them had been treated with breast preservation (tumour size: 2 x T2,1 x T3) and 4 with a mastectomy (tumour size: 2 x T3,2 x T4). None of them had oncoplastic surgery. The local recurrence rate for patients with breast conserving surgery was significantly lower (2,2%) than the rate for patients with mastectomy (12,9%)(chi square p=0,02).

Conclusion: Breast conserving therapy in patients with locally advanced breast cancer after preoperative chemotherapy is possible and safe without compromising a higher local recurrence rate. Although the numbers were small pts with mastectomy showed a significant higher rate, possibly due to a larger tumour size.

[ P ~ Survival over 57 months despite high level of thrombopenia caused by bone marrow carcinosis of primary metastatic breast cancer

V. Bjelic Radisic 1 , H. Stager, R. Winter, E. Petru. ~ Medical University Graz, Departartment of Gynaecology and Obstetrics, Graz, Austria; 2 Medical University Graz, Department of Oncology, Graz, Austria

7-10% of all patients with breast cancer show primary distant metastases. Primary metastatic breast cancer with bone marrow carcinosis (documented by bone marrow biopsy) and a high level of thrombopenia at the time of the first diagnosis is very rare.

We describe a case of a 62 year-old patient with primary metastatic, ex- ulcerated, invasive ductal breast cancer, ER/PR +, Her-2 +++, bone mar- row carcinosis, lung and frontoparietal metastases and initial thrombope- nia of 15.000/mm 3 We started with very aggressive chemotherapy (dox- orubicin and docetaxel) expecting that the cytotoxic effect on bone mar- row will stimulate the production of thombocytes. However, this effect could not be confirmed. Because of non response or progression of tumour the patient was treated with capecitabine (10 cycles), examestan, CMF (6 cycles),vinorelbine (11 cycles), gemcitabine (11 cycles),carboplatin (4 cy- cles),trastuzumab during the next 57 months. She was also treated by pal- liative radiotherapy for her frontoparietal and pelvic metastases. The best effect with regard to clinical stabilisation of the disease was reached by the administration of capecitabine, exemestan, gemcitabine and trastuzumab. Most frequently the level of platelets during chemoterapy was less than 10.000/mm 3 without haemorrhage. The patient had a platelet transfusion at 2.000/mm 3 platelets only twice. The tumour markers CEA and CA15/3 showed no correlation with the clinical status or platelet count. This case showed that survival of single patients despite initial metastases of bone marrow with application of different standard chemotherapy, antihormone therapy and monoclonal antibody is possible over five years. Thrombope- nia did not cause complication. So it was possible to stabilise the patient's disease and improve the quality of life for several months.

~ 0 - ~ Sentinel lymph node biopsy after neoadjuvant chemotherapy

L.C.B. Prado ~ , G. Garcia ~ , A. Yoshimura ~ , C. Aldrighi 1 , M. Bernardini 1 , A. Nisida 1 , E. Chagas 2, L. Silva 2, E Brenelli 2, J. Rodrigues 3 . i S~o Paulo Universi~ Gynecology, S&o Paulo, Brazil; 2 European Institut of Oncology, Breast Division, Milan, Italy; 3 UNESP, Gynecology, Botucatu, Brazil

Background: Sentinel lymph node biopsy (SLNB) procedure is a method for ascertaining the axillary lymph node status in patients with breast can- cer, as the SLN has been shown to have predictive value for the status of the remaining axillary lymph nodes. Patients undergoing the SLNB proce- dure have less morbidity after the surgery. However, there are many doubts about the indications of this method. A false-negative case could be very dangerous to the patient. One controversy of the SLNB is the occorrence of neoadjuvant chemiotherapy (NC) before the surgery. So, the authors studied prospectively the rate of identification, sensibility and accuracy of SLNB after NC.

Method: Between May/1999 and January/2002, 26 women with invasive ductal carcinoma of the breast, who had received NC, with adriamicin and cyclophosphamide, were selected. These patients were submitted to SLNB and total axillary dissection (TDA) at the same surgery in the Breast De- partment of S~.o Paulo University. The chosen patients had tumors with less than 3,0cm (medium size = 1,63cm) after the NC. SLNB was performed with dextran 70 solution marked with technetium-99m (Tc-99) injected near the tumor. All sentinel nodes were analyzed with H&E and immunohistochemical analysis. The same procedure was adopted for the others nodes.

Results and Conclusions: The SLN identification rate was 96,1% (25/26). In these 25 cases, the accuracy of the SLN to predict the axillary status was 96,0%, with 100% of the specificity and 90% sensibility (1 false- negative). SLNB is a minimally invasive technique that can be used to evalu- ate the regional nodal status of patients. Despite some controversy in other

studies, the success rate of sentinel node identification in this study does not seem to be altered after neoadjuvant therapy. This study suggests that we can believe in the SLNB method even in cases of NC.

[ • Brain as a sanctuary site for early relapse in patients with advanced breast cancer treated with trastuzumab

i2 Yau 1. i Royal Marsden Hospital, Department of Medicine, Sutton, UK

Introduction: Recent studies suggested a high incidence of brain metas- tases in patients with advanced breast cancer who have previously received trastuzumab. We aimed to investigate whether brain was a sanctuary site for early relapse and whether brain metastases are a main cause of mortality in this patient cohort.

Patients and Methods: Ninety-four patients who had received trastuzumab for advanced breast cancer from November 1999 to Septem- ber 2003 at the Royal Marsden Hospital were assessed. Survival data were assessed by the Kaplan-Meier method.

Results: With a median follow up period of 11 months from commenc- ing trastuzumab, 23 patients developed brain metastases (30% at 1 year; 95% CI 58-82%). 35 patients responded to trastuzumab and 22 achieved disease stabilization. Among these 57 patients who had clinical benefits on trastuzumab, 11(19%) suffered cerebral relapse as their first site. Isolated brain metastases were the initial site of progression for 14% of patients who received first line trastuzumab treatment. Patients with visceral disease at the time of trastuzumab therapy were marginally more likely to develop brain metastases (p=0.09). 77% of deaths were due to progression of brsuggested to assess the value of prophylactic cranial irradiation in this patient cohort. ain metastases.

Discussion: This study implicates the brain as a sanctuary site for early relapse in HER2 positive patients receiving trastuzumab. Furthermore, cere- bral relapse is the main cause of death. Randomised clinical trials are needed.

[ • Cellular immunotherapy in late stage breast cancer patients with reactivated autologous Memory T-cells derived from bone marrow

F. Schuetz 1 , K. Ehlert 1 , I. Diel 2, V. Schirrmacher 3, A. Schneeweiss 1 , G. Bastert 1 , H. Strittmatter 1 , C. Sohn ~ , P. Beckhove 3. i University Clinics Heidelberg, Gynecology and Obstetrics, Heidelberg, Germany; 2 CGG-Clinic, Gynecological Oncology, Mannheim, Germany; 3 Deutsches Krebsforschungszentrum, Immunology, Heidelberg, Germany

Tumorspecific Memory T-cells (MTC) can be found in the bone marrow (BM) in the majority of primary and metastatic breast cancer (BC) patients by us- ing ELISpot-analysis. Upon specific restimulation with tumourantigen-pulsed dendritic cells (DC) autologous T-cells exert specific effector functions like IFN-gamma production and cytotoxicity. Furthermore we have shown in NOD/Scid-mice that reactivated MTC are able to infiltrate autologous and heterologous tumor tissue, proliferate and kill tumor cells by induction of apoptosis, leading to a marked or complete tumor rejection within 21 days after transfer (Nature Med, 2001). Endocrine and cytostatic cancer therapies only have a limited influence on the frequency of tumorspecific MTC in BM of BC patients. In a phase-I trial 15 patients with metastatic BC (inclusion criteria) were treated with autologous reactivated MTC of BM. Primary ob- jective were feasbility, and toxicity, secondary were clinical response, and im- munomonitoring. After testing patient's BM for the presence of tumorspecific MTC those cells were reactivated by incubating them in vitro with autologous DC pulsed MCF-7 lysate for 12 days. Reactivated T-cells and pulsed DCs were injected once intravenously. Follow Ups were done after 7, 14, 21, 28, and 120 days. Study design was feasible in every way. There were no side effects found during and after T-cell injection. There was a partial response in 3 of 5 measurable patients. We conclude that cellular immunotherapy with autologous reactivated MTC is an innovative way of BC treatment. We thus prepare a phase-II trial in metastatic and primary BC patients.