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Monotherapy with docetaxel in the second- or third-line treatment of anthracycline-resistant metastatic breast cancer
FRIDAY,
SEPTEMBER
FC5.02 BREAST
CANCER:
8
15
DIAGNOSIS
AND TREATMENT
FC5.02.01 VALUE OF FUNCTIONAL BLOOD SUPPLY PAlTERN ANALYSIS IN THE DETECTION OF EARLY BREAST CANCER G.C. Montruccoli, D. Montruccoli-Salmi, D. Barnab&, Dept. OB/GYN, Toniolo Clinic, Bologna, Italy. Objectives: Since angiogenesis plays a fundamental role in all steps of carcinogenesis, we reviewed the histologic findings of biopsies performed on indication of our pattern analysis of the functional blood supply of the breasts in a large series of women. Study Methods: Since January 1978,5.672 evaluable self-referred women (symptomatic and non-symptomatic) of all ages from the onset of puberty (lo-86yr.) were examined in our Dept. utilizing special thermographic plates applied on the skin for a few seconds in a painless and non-invasive manner. The method is called dynamic angiothermography (DATG). When appropriate, x-ray mammography and/or ultrasound was also performed. Results: One or more excisional biopsies were performed on 589 patients on indication of DATG. Of a total of 656 specimens, 31% were non-epithelial lesions or adenomas and 69% were epithelial lesions, including 16.5% ductal hyperplasias, 23% florid hyperplasias, 4.5% papillomas, 4% lobular/ductal atypia, 6% lobular and/or ductal carcinoma in situ, 1% microinvasive carcinomas and 14% invasive carcinomas. Conclusions: These results indicate that DATG is capable of revealing very small cancerous and precancerous lesions, the latter being present in a high percentage of biopsies. Since the outcome of breast cancer currently depends on early diagnosis more than therapy, the possibility of revealing small cancerous and precancerous lesions can be useful to improve the prognosis of the disease. A number of biopsies performed on indication of DATG confirmed the presence of angiogenesis in the very early stages of carcinogenesis.
FC5.02.02 LOBULAR (AS WELL AS DUCTAL) IN-SITU CARCINOMA OF THE BREAST CAN BE REVEALED BY STUDY OF THE FUNCTIONAL BLOOD SUPPLY D. Montruccoli-Salmi, D. Barnab&, G.C. Montruccoli, Dept. OB/GYN, Toniolo Clinic, Bologna, Italy. Objectives: Whereas ductal in-situ carcinoma (DCIS) of the breast may be revealed by x-ray mammography, lobular in-situ carcinomas (LCIS) generally appear only as infrequent casual findings (due to their lack of specific mammographic signs and non-palpable nature). We investigated whether preinvasive lobular breast lesions may be detected by the study of the functional blood supply. Study Methods: We retrospectively evaluated the frequencies of noncasual histological findings of preinvasive lobular and ductal lesions among 5,672 self-referred women (symptomatic and non-symptomatic) of all ages (lo-82 yr) examined since January 1978 in our department by means of a new technique called dynamic angiothermography (DATG). DATG is based on the examination and monitoring of individual functional blood supply patterns as revealed by images obtained from special thermographic plates that are placed on the skin for a few seconds in a painless and non-invasive manner. Results: Among a total of 656 excisional biopsies made on specific indication of DATG, we found 28 cases of pure LCIS versus 15 cases of pure DCIS. Furthermore, 23 cases of atypical lobular hyperplasia (ALH) were detected, versus 7 cases of atypical ductal hyperplasia (ADH). In addition to these pure lobular and pure ductal lesions, mixed lobular/ductal lesions were also detected: 15 cases of LCIS/DCIS and 13 cases of ALWADH. Conclusion: Whereas DCIS is detected much more frequently than LCIS throughout the literature, our experience with DATG revealed about twice as many preinvasive lobular lesions with respect to ductal ones. We believe that blood supply pattern analysis by means of DATG may offer a practical diagnostic method for the detection of preinvasive lobular breast lesions.
FC5.02.03 FRAClXL GROWTH KINETICS OF BREAST CANCER CELLS R. Sedivvl; Ch. Windischberger2; A.C. Budinsky3, W.J. KGstler3, and C.C. Zielinski3,4,5 1 Clinical Institute of Clinical Pathology, 2 Institute of Medical Physics, 3 Department of Medicine I, Clinical Division of Oncology, 4 Chair of Medical, Experimental Oncology, 1-3 University Hospital and 5 Ludwig Boltzmann. Institute for Clinical Experimental Oncology, Vienna, Austria. Fractal geometry and chaos theory have gained increasing attention in cancer research over the past years. The interpretation of carcinogenesis representing a dynamical system gone awry opens up new options of analysis and description. One of these options describes tumor growth in a holistic manner by phase space reconstruction for displaying the spatiotemporal distribution of certain system parameters. Another option describes the graphical complexity of the spatio-temporal distribution by measuring its fractal dimension. Thus, we used these analytical tools to describe growth kinetics by embedding the counts of thymidin uptake of breast cancer cell lines in phase space diagramms, and determined the fractal dimension of the system’s trajectories. 3H-thymidin uptake was studied in breast cancer cells (ZR-75-1, SK-BR-3, MCF-7) and compared to results obtained with benign HBL-100 cells. Data of untreated and Tumour Necrosis Factor (TNF)-a treated cells were plotted in 3D phase space diagrams to visualize growth dynamics. TNF-a clearly exerted a higher fractal dimension than non-treated cell culture lines. This study shows that mapping growth kinetics by phase space reconstruction represents a valuable tool for visualizing growth parameters such as proliferation assessed by 3H-thymidin uptake in breast cancer cell lines. In addition, the change of the fractal dimension quantified the TNF-a effect. Techniques of fractal geometry and chaos theory thus could be used to visualize growth kinetics for quantifying growth-modulating effects of various apoptosis-inducing substances Fractal Dimension (DF) of the pseudo attractor compared to p-values of mean cpm counts of TNF-a treated versus non-treated cells Cells No treatment TNF treatmentFD difference P-value (a=0,05) Hbl-100 1,339 1,345 0,006 p=o,o4 ZR-75-l 1,356 1,467 0,111 p
FC5.02.04 MONOTHERAPY WITH DOCETAXEL IN THE SECOND- OR THIRDLINE TREATMENT OF ANTHRACYCLINE-RESISTANT METASTATIC BREAST CANCER. T. Brodowicz’, W.J. K&tler’, S. Tomek’, I. Vaclavik’, V. Herscovici’, C. Wiltschke’, G.G. Steger’ And C.C. Zielinski’,z,5 ‘Clinical Division of Oncology and ’ Chair for Medical Experimental Oncology, Department of Medicine I, University Hospital, and 5Ludwig Boltzmann Institute for Clinical Experimental Oncology, Vienna, Austria. Objectives: The present study was undertaken to evaluate the efficacy of single agent docetaxel as an active drug in second- and third-line treatment in patients with metastatic breast cancer. Study Methods: Overall, 19 patients with breast cancer pretreated with one or two anthracycline-based regimens for visceral metastases were enrolled to receive intravenous docetaxel 100 mg/mz on day 1, q21d. Docetaxel was administered as second-line therapy in 11 patients, whereas 8 patients received docetaxel in a third-line setting. Results: In the second-line-setting, complete response (CR) was achieved in 2 (lE%), partial response (PR) in 4 (36%) and stable disease (SD) in 3 (27%) patients resulting in a response rate (RR) of 54%. In the third-linesetting 3 (38%) patients experienced PR (RR 38%) and 2 (25%) SD. In the second-line-setting, median time to progression was 6.5 f 3.9 months (range: 2.1-15.8) versus 4.7 f 5.5 months (range: 0.6-15.9) in the third-line setting. Median overall survival was 9.6 f 8.0 months (range: 2.7-25.8) vs. 11.2 f 6.1 months (range: 4.8-18.7). None of the patients experienced treatment-limiting toxicities. Conclusions: We conclude that docetaxel induced responses in 48% of anthracycline-resistant patients enrolled into the present study. The safety profile of docetaxel was manageable and tolerable. Docetaxel represented efficacious treatment in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy.
SEPTEMBER
FC5.02 BREAST
CANCER:
8
15
DIAGNOSIS
AND TREATMENT
FC5.02.01 VALUE OF FUNCTIONAL BLOOD SUPPLY PAlTERN ANALYSIS IN THE DETECTION OF EARLY BREAST CANCER G.C. Montruccoli, D. Montruccoli-Salmi, D. Barnab&, Dept. OB/GYN, Toniolo Clinic, Bologna, Italy. Objectives: Since angiogenesis plays a fundamental role in all steps of carcinogenesis, we reviewed the histologic findings of biopsies performed on indication of our pattern analysis of the functional blood supply of the breasts in a large series of women. Study Methods: Since January 1978,5.672 evaluable self-referred women (symptomatic and non-symptomatic) of all ages from the onset of puberty (lo-86yr.) were examined in our Dept. utilizing special thermographic plates applied on the skin for a few seconds in a painless and non-invasive manner. The method is called dynamic angiothermography (DATG). When appropriate, x-ray mammography and/or ultrasound was also performed. Results: One or more excisional biopsies were performed on 589 patients on indication of DATG. Of a total of 656 specimens, 31% were non-epithelial lesions or adenomas and 69% were epithelial lesions, including 16.5% ductal hyperplasias, 23% florid hyperplasias, 4.5% papillomas, 4% lobular/ductal atypia, 6% lobular and/or ductal carcinoma in situ, 1% microinvasive carcinomas and 14% invasive carcinomas. Conclusions: These results indicate that DATG is capable of revealing very small cancerous and precancerous lesions, the latter being present in a high percentage of biopsies. Since the outcome of breast cancer currently depends on early diagnosis more than therapy, the possibility of revealing small cancerous and precancerous lesions can be useful to improve the prognosis of the disease. A number of biopsies performed on indication of DATG confirmed the presence of angiogenesis in the very early stages of carcinogenesis.
FC5.02.02 LOBULAR (AS WELL AS DUCTAL) IN-SITU CARCINOMA OF THE BREAST CAN BE REVEALED BY STUDY OF THE FUNCTIONAL BLOOD SUPPLY D. Montruccoli-Salmi, D. Barnab&, G.C. Montruccoli, Dept. OB/GYN, Toniolo Clinic, Bologna, Italy. Objectives: Whereas ductal in-situ carcinoma (DCIS) of the breast may be revealed by x-ray mammography, lobular in-situ carcinomas (LCIS) generally appear only as infrequent casual findings (due to their lack of specific mammographic signs and non-palpable nature). We investigated whether preinvasive lobular breast lesions may be detected by the study of the functional blood supply. Study Methods: We retrospectively evaluated the frequencies of noncasual histological findings of preinvasive lobular and ductal lesions among 5,672 self-referred women (symptomatic and non-symptomatic) of all ages (lo-82 yr) examined since January 1978 in our department by means of a new technique called dynamic angiothermography (DATG). DATG is based on the examination and monitoring of individual functional blood supply patterns as revealed by images obtained from special thermographic plates that are placed on the skin for a few seconds in a painless and non-invasive manner. Results: Among a total of 656 excisional biopsies made on specific indication of DATG, we found 28 cases of pure LCIS versus 15 cases of pure DCIS. Furthermore, 23 cases of atypical lobular hyperplasia (ALH) were detected, versus 7 cases of atypical ductal hyperplasia (ADH). In addition to these pure lobular and pure ductal lesions, mixed lobular/ductal lesions were also detected: 15 cases of LCIS/DCIS and 13 cases of ALWADH. Conclusion: Whereas DCIS is detected much more frequently than LCIS throughout the literature, our experience with DATG revealed about twice as many preinvasive lobular lesions with respect to ductal ones. We believe that blood supply pattern analysis by means of DATG may offer a practical diagnostic method for the detection of preinvasive lobular breast lesions.
FC5.02.03 FRAClXL GROWTH KINETICS OF BREAST CANCER CELLS R. Sedivvl; Ch. Windischberger2; A.C. Budinsky3, W.J. KGstler3, and C.C. Zielinski3,4,5 1 Clinical Institute of Clinical Pathology, 2 Institute of Medical Physics, 3 Department of Medicine I, Clinical Division of Oncology, 4 Chair of Medical, Experimental Oncology, 1-3 University Hospital and 5 Ludwig Boltzmann. Institute for Clinical Experimental Oncology, Vienna, Austria. Fractal geometry and chaos theory have gained increasing attention in cancer research over the past years. The interpretation of carcinogenesis representing a dynamical system gone awry opens up new options of analysis and description. One of these options describes tumor growth in a holistic manner by phase space reconstruction for displaying the spatiotemporal distribution of certain system parameters. Another option describes the graphical complexity of the spatio-temporal distribution by measuring its fractal dimension. Thus, we used these analytical tools to describe growth kinetics by embedding the counts of thymidin uptake of breast cancer cell lines in phase space diagramms, and determined the fractal dimension of the system’s trajectories. 3H-thymidin uptake was studied in breast cancer cells (ZR-75-1, SK-BR-3, MCF-7) and compared to results obtained with benign HBL-100 cells. Data of untreated and Tumour Necrosis Factor (TNF)-a treated cells were plotted in 3D phase space diagrams to visualize growth dynamics. TNF-a clearly exerted a higher fractal dimension than non-treated cell culture lines. This study shows that mapping growth kinetics by phase space reconstruction represents a valuable tool for visualizing growth parameters such as proliferation assessed by 3H-thymidin uptake in breast cancer cell lines. In addition, the change of the fractal dimension quantified the TNF-a effect. Techniques of fractal geometry and chaos theory thus could be used to visualize growth kinetics for quantifying growth-modulating effects of various apoptosis-inducing substances Fractal Dimension (DF) of the pseudo attractor compared to p-values of mean cpm counts of TNF-a treated versus non-treated cells Cells No treatment TNF treatmentFD difference P-value (a=0,05) Hbl-100 1,339 1,345 0,006 p=o,o4 ZR-75-l 1,356 1,467 0,111 p
FC5.02.04 MONOTHERAPY WITH DOCETAXEL IN THE SECOND- OR THIRDLINE TREATMENT OF ANTHRACYCLINE-RESISTANT METASTATIC BREAST CANCER. T. Brodowicz’, W.J. K&tler’, S. Tomek’, I. Vaclavik’, V. Herscovici’, C. Wiltschke’, G.G. Steger’ And C.C. Zielinski’,z,5 ‘Clinical Division of Oncology and ’ Chair for Medical Experimental Oncology, Department of Medicine I, University Hospital, and 5Ludwig Boltzmann Institute for Clinical Experimental Oncology, Vienna, Austria. Objectives: The present study was undertaken to evaluate the efficacy of single agent docetaxel as an active drug in second- and third-line treatment in patients with metastatic breast cancer. Study Methods: Overall, 19 patients with breast cancer pretreated with one or two anthracycline-based regimens for visceral metastases were enrolled to receive intravenous docetaxel 100 mg/mz on day 1, q21d. Docetaxel was administered as second-line therapy in 11 patients, whereas 8 patients received docetaxel in a third-line setting. Results: In the second-line-setting, complete response (CR) was achieved in 2 (lE%), partial response (PR) in 4 (36%) and stable disease (SD) in 3 (27%) patients resulting in a response rate (RR) of 54%. In the third-linesetting 3 (38%) patients experienced PR (RR 38%) and 2 (25%) SD. In the second-line-setting, median time to progression was 6.5 f 3.9 months (range: 2.1-15.8) versus 4.7 f 5.5 months (range: 0.6-15.9) in the third-line setting. Median overall survival was 9.6 f 8.0 months (range: 2.7-25.8) vs. 11.2 f 6.1 months (range: 4.8-18.7). None of the patients experienced treatment-limiting toxicities. Conclusions: We conclude that docetaxel induced responses in 48% of anthracycline-resistant patients enrolled into the present study. The safety profile of docetaxel was manageable and tolerable. Docetaxel represented efficacious treatment in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy.