Electronic Library of Scientific Literature


Volume 44 / No. 1 / 1997

Incidence and kinetics of distant metastases in patients with operable breast cancer

M. Kryj, B. Maciejewski, H.R. Withers, J.M.G. Taylor

Department of Surgery, Cancer Center, MSC Institute, Gliwice, Poland;
Department of Radiotherapy, Cancer Center MSC Memorial Institute, 44-101 Gliwice, Poland;
Department of Radiation Oncology, Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, USA;
Department of Biostatistics, Jonsson Comperehensive Cancer Center, UCLA, Los Angeles, CA, USA

The purpose of this paper is to evaluate the incidence and kinetics of distant metastases in operable breast cancer and to relate these estimates to various tumor and patient characteristics. The records of 309 consecutive patients with operable breast cancer in stage T1-4N0-1M0 were reviewed, and the incidence of distant metastases (DM) and death due to DM were evaluated. 195 patients had positive axillary nodes with the following distribution of the number of nodes: 45% had 1-2 node, 16% had 3-4 nodes, 14% and 25% had 5-7 and more nodes, respectively. All patients were treated with radical mastectomy with axillary nodes dissection (the only treatment in 39% of cases). In 198 cases radical mastectomy was combined with radiotherapy and/or chemotherapy given pre- or postoperatively. Hormonal treatment was given in 27% of cases. Minimum follow-up was 10 years. Distant metastases were found in 150 cases (49%) and in 78 cases (25%) they developed early, during the first 18 months follow-up. Average rate of DM in N0 cases was 25%. Number of involved nodes and extracapsular invasion were found significant and independent prognostic factors. High risk (50%) of DM and death due to DM correlate with age <40 y, premenopausal status, tumor stage >=T3, more than 2 axillary nodes and/or extracapsular invasion. The linearity of the curves for freedom from DM and for freedom from death due to the DM suggest uniform distribution of progression rates with a median value for halving time for freedom from early DM of about 8 months, and of about 40 months for freedom from the DM occuring later than 18 months, being for whole group an average of 20 months. High incidence of DM is a significant cause of poor long-term survival. Early appearance (< 18 month follow-up) of about half of the DM suggests that they are already present as subclinical micrometastases at the time of initial loco-regional treatment. The time of appearance of distant metastases is consistent with a wide range of metastatic cell burdens among patients. Systemic therapy, at least for selected group of patients, might decrease the incidence of DM and improve long-term results.

Key words: Operable breast cancer, distant metastases, incidence, kinetics, systemic treatment.
str. 3-11

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Prognostic parameters in low-grade non-Hodgkin's lymphomas

T. Zemunik, J. Vuèkoviæ, G. Forenpoher, N. Kneževiæ, N. Štula, M. Dubravèiæ, I. Ribièiæ, A. Rozga

Department of Biology, Zagreb University School of Medicine Split Branch, 21000 Split, Croatia;
Department of Hematology, Health Center "Split", Split, Croatia;
Department of Pathology, Hematology and Oncology, Clinical Hospital "Split", Split, Croatia;
Faculty of Economy, Split, Croatia

In a group of 73 patients with low-grade non-Hodgkin's lymphomas (LG NHL) a multivariate analysis of the following variables was performed: pathological types following the International Working Formulation, clinical stage, B-symptoms, erythrocyte sedimentation rate, hemoglobin level, white blood cell and lymphocyte count, serum gamma globulin level, serum total lactic dehydrogenase (LDH) level, mitotic and complete remission. The patients with lymphocytic lymphoma manifested the best survival in this group. Low-proliferative lymphomas showed better survival than high-proliferative lymphomas at 3 and 10 years. B-symptoms, serum total LDH level and complete remission were significant independent prognostic factors.

Key words: Low grade lymphoma, prognostic factors.
str. 13-17

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Clinical thermoradiotherapy: The influence of some prognostic parameters on recurrence-free survival

H. Lešnièar

Institute of Oncology, 1000 Ljubljana, Slovenia

Thirty-one patients with loco-regional advanced tumors accessible for local thermoradiotherapy were treated at the Institute of Oncology in Ljubljana, between 1989-1993. There were six primary inoperable and 25 recurrent or residual tumors after previous radiotherapy. In 13 patients treatment consisted of combined interstitial water hyperthermia and brachyradiotherapy, in 5 patients combination of interstitial hyperthermia and percutaneous radiotherapy was used, and percutaneous microwave hyperthermia with percutaneous irradiation was employed in remaining 13 patients. Complete response (CR) was achieved in 17/31 (55%) of all treated patients. Among various tumoral and therapeutic parameters tested significant influence on complete response rate was found for tumor volume (p = 0.047), minimum intratumoral temperature (p = 0.004), time interval between hyperthermia and radiotherapy (p = 0.02), and fraction-size of immediate radiotherapy (p = 0.002).
More than one hyperthermia treatment and total tumor dose of irradiation >45 Gy did not significantly improve local control rate in our patients. For all 31 patients treated with thermoradiotherapy 3-year recurrence-free survival (RFS) of 41% was achieved. For the group of 9 patients in whom the interval between hyperthermia and irradiation exceeded 1 hour, RFS of 18% compared to 53% for 22 patients treated with "synchronous" thermoradiotherapy was achieved, however the difference between the groups was not significant (log rank p = 0.17). In 25 patients in whom minimum intratumoral temperature (Tmin50) exceeded 42.5°C significant difference in RFS between the subgroups of 19 patients treated synchronously and 6 patients in whom time interval between the two modalities was longer than 1 hour, i.e. 65% vs. 25% respectively, was found (log rank p = 0.048). However, most favorable RFS of 81% was achieved in the subgroup of 15 patients in whom good hyperthermia treatment (Tmin50 >= 42.5°C) was followed by an immediate irradiation using fraction size >= 3 Gy (p = 0.015). Treatment related toxicity was acceptable and did not correlate with response rate. Our conclusion is that thermoradiotherapy is more effective when somewhat larger fraction-size of radiotherapy than conventional, i.e. 3-5 Gy, are employed in synchronous combination of both treatment modalities.

Key words: Local hyperthermia, radiotherapy, malignant tumors, clinical treatment.
str. 19-24

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In vitro and in vivo studies of murine sarcoma cells after prolonged treatment with promoting phorbol ester TPA

P. Janik, B. Woynarowska, J. Mi³oszewska, B. Szaniawska

Department of Cell Biology, Cancer Center Institute of Oncology, 02 781 Warsaw, Poland;
University of Texas, Health Science Center at San Antonio, TX, USA

Murine sarcoma cell line (L-1) treated with promoting phorbol ester (TPA) showed decreased content and activity of protein kinase C (PKC) as measured by Western blotting and histone phosphorylation methods. The PKC depleted line (L-1R) produced bigger, tumors after s.c. transplantation into syngeneic mice and more spontaneous and artificial metastases developing after i.v. injection of tumor cells.
The in vitro studies revealed decreased: adhesiveness, migratory and invasiveness properties of PKC depleted cells. Negative correlation between in vitro and in vivo studies were found.

Key words: Metastases, protein kinase C, invasion
str. 25-29

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Growth-regulating influence of nonactivated resident macrophages on transformed and tumor cells in the in vitro contact interactions

L.G. Burdelya

Institute of Carcinogenesis, Cancer Research Centre, Academy of Medical Sciences, 115 478 Moscow, Russia

Susceptibility to cytostatic activity of nonactivated macrophages (Mph) of Syrian hamster embryo fibroblasts (HEF) transformed in vitro by BAV-3, SV40, RSV-SR, or spontaneously and of their in vivo selected variants was studied in dynamics (5 days of co-incubation). With the use of 3H-TdR incorporation test it was demonstrated that HEF transformed by BAV-3 appeared to be able to overcome the cytostasis at 4-5 day of the co-incubation with Mph, in contrast to deeply suppressed spontaneously transformed cells of STHE strain. HEF transformed by SV40, or RSV-SR appeared to be resistant to growth-inhibiting activity of Mph during almost all the 5-day period. The in vivo selected malignant variants of STHE cells were able to recover from cytostasis after 4-5 days of the co-incubation with nonactivated Mph, in contrast to low-malignant variant and to parental cell strain.

Key words: Macrophages, transformation, tumor cells, cytostasis.
str. 31-35

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Retinoic acid-induced alteration of cell surface topography and other changes in an oral carcinoma cell line in culture

R. Sarkar, S.K. Das

Chittaranjan National Cancer Institute, 700 026 Calcutta, India

Nature of antiproliferative action of retinoic acid (RA) on KB cells was studied by using monolayer and agar culture techniques. RA-treated cultures showed increased requirement of serum for their growth. Growth of colonies in agar culture was significantly retarded when cells were treated with 40 µmol RA. RA-induced growth inhibitions in both monolayer and agar cultures were independent of cell seeding densities. Cortisone and hydrocortisone showed no reversal of the inhibitory effects induced by RA on KB cells. Scanning electron microscopy study revealed a significant alteration in cell surface topography of RA-treated cells in monolayer culture. The results demonstrate that RA has a potential of reversing some of the properties which are associated with transformed state of oral carcinoma cells.

Key words: Retinoic acid, oral carcinoma, surface topography.
str. 37-43

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Glutathione and glutathione metabolizing enzymes in tissues and blood of breast cancer patients

J. Gromadziñska, W. W¹sowicz, M. Andrijewski, M. Sk³odowska, O. Zambrano Quispe, P. Wo³kanin, B. Olborski, A. P³u¿añska

Department of Toxicity Evaluation, Nofer's Institute of Occupational Medicine, 90-950 Lodz, Poland;
Department of Toxicology, Military Medical Academy, Lodz, Poland;
Department of Plant Physiology and Biochemistry, University of Lodz, Lodz, Poland;
Department of Chemotherapy, Oncology Center of Medical Academy, Lodz, Poland;
Department of Ultrastructural Pathology, Military Medical Academy, Lodz, Poland

Many reports indicate that glutathione and enzymes cooperating with it are important in neoplastic processes. Glutathione (GSH) concentrations and glutathione S-transferase (GSH STr) and glutathione peroxidase (GSH-Px) activities were determined in breast cancer tissue and adjacent healthy tissues, as well as in blood of 28 patients. There were considerable differences in the investigated parameters among individual patients. Therefore we analyzed the paired samples of normal and cancerous tissues from the same individual. In 68% of the patients the activities of GSH-Px and in 85% patients those of GSH STr were found to be higher in the tumor than in the normal tissue. GSH concentration in 48% tumor samples were higher and in 44% lower than in corresponding normal tissues. Statistically significant correlation was found between GSH-Px and GSH STr in normal (r = 0.51, p < 0.005) and in cancer tissues (r = 0.64, p = 0.001). Correlation coefficient between GSH Px activity in normal and corresponding cancer tissues was r = 0.71 (p < 0.001), however this correlation in the case of GSH STr was much lower but still significant (r = 0.38, p < 0.05). No significant correlation in the determined parameters was found between erythrocytes or plasma and normal or cancer tissues.

Key words: Glutathione, glutathione peroxidase, glutathione S-transferase in blood, in cancer tissues, breast cancer.
str. 45-51

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Phylloid breast tumors and three steroid hormone receptors

B.A. Lang, I. Vermousek, M. Šimíèková, M. Èernoch, M. Nekulová, Z. Paèovský, A. Rejthar

Masaryk Memorial Cancer Institute, 656 53 Brno, Czech Republic

The concentrations of three steroid hormones (estrogen, progesteron and 1,25-dihydroxycholecalciferol) receptors (ER, PgR, DR) in tissue cytosol were analyzed in a group of 17 breast phylloid tumors. Comparison with breast carcinoma tissue samples (n = 37) did not reveal significant differences in average values of ER, PgR, and DR. Comparison with another control set of 30 samples of dysplastic tissue of the mammary gland showed significant differences only in PgR values. Only 18% of phylloid tumor samples contained levels above cut-of-line of all three receptors (ER, PgR, DR - 5,10,10 resp. fmol//mg protein). The most frequent combination was ER+PgR+DR- (41%). As far as we know, DR in phylloid breast tumors have never been examined before. In approximately 60% of our samples we found the expression of DR, in 36% the estimated values were above 10 fmol/mg protein. Cells of the tissue not expressing DR seem to belong to a special phenotype. We found no ER+PgR- or ER-PgR- combinations in them. The group which expresses DR is characterized by a higher dispersion of PgR values.

Key words: Breast phylloid tumors, estrogen receptor, progesteron receptor, vitamin D receptor.
str. 53-57

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Familial testicular cancer and developmental anomalies

D. Ondruš, D. Kuba, S. Chreòová, J. Maťoška

Department of Urology, Comenius University Medical School, Dérer Memorial Hospital, 833 05 Bratislava, Slovakia;
Department of Clinical Immunology, Institute of Preventive and Clinical Medicine, Bratislava, Slovakia;
Department of Pathology, St. Elizabeth Cancer Institute, Bratislava, Slovakia

Familial occurrence belongs to factors followed in etiology and pathogenesis of testicular germ-cell tumors. Association with abnormal testicular development, or with other risk factors is relatively frequent. In our material 650 patients had been treated for testicular cancer in the period of 1981-1995. Familial occurrence was observed 7-times (1.08%), most frequently in combination with cryptorchidism. Individual families were analyzed in details, including HLA typing. On basis of the observations the supplementation of initial examination of each patient with suspicious testicular cancer with detailed familial history aimed also at the occurrence of urogenital developmental anomalies and tumors has been recommended. The knowledge about familial tumor occurrence in the first-degree relatives in combination with thorough testicular self-examination is being considered of great importance in the secondary prevention.

Key words: Testicular cancer, familial tumor occurrence, cryptorchidism, HLA antigens.
str. 59-61

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Richter syndrome with emphasis on large-cell non-Hodgkin lymphoma in previously unrecognized subclinical chronic lymphocytic leukemia

Sv. Jeliæ, V. Jovanoviæ, N. Milanoviæ, M. Marinkoviæ, V. Kovèin, D. Miloševiæ, M. Vlajiæ

Institute of Oncology and Radiology, 11000 Belgrade, Yugoslavia;
Institute of Pathology of the Medical faculty, Belgrade, Yugoslavia

The authors report seven cases of Richter's syndrome, i.e. of large-cell non-Hodgkin's lymphoma (NHL) arising in association with chronic lymphocytic leukemia (CLL). Six patients had the recently recognized variant of this syndrome, occurring in patients with previously undiagnosed subclinical CLL. All patients were treated with aggressive chemotherapy and a complete response of large cell NHL was achieved in 4/7. A complete response of NHL was observed in 3 out of 6, and a partial response in 2/6 patients with simultaneous occurrence of subclinical CLL and large cell NHL (response rate 5/6). Our findings might suggest that patients with Richter syndrome occurring in previously undiagnosed subclinical CLL could represent a better prognostic group in the overall population of patients with large cell NHL transformation of CLL.

Key words: Richter syndrome, non-Hodgkin lymphoma, subclinical chronic lymphocytic leukemia, chemotherapy.
str. 63-68

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Possible role of indoor environment and coal combustion emission in lung carcinogenesis in Fuyuan County, China

Y. Nakanishi, S. Chen, S. Inutsuka, Y. Ma, X. Jiang, N. Hara, N. Sera, H. Tokiwa

Research Institute for Diseases of the Chest, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashiku, Fukuoka, 812-82, Japan;
Kunming Medical College, Kunming, Yunnan, P.R. China;
Fukuoka Institute for Health and Environmental Sciences, Dazaifu, Fukuoka, Japan;
Kyushu Women's University, 1-1 Jiyugaoka, Yahatanishiku, Kitakyushu 807, Japan

Fuyuan Country, in Yunnan Province, China has an extremely high lung cancer mortality both in males and non-smoking females. Out of 5768 deaths, 588 patients died of malignant diseases. Lung cancer was the number one cause of death among malignant diseases both in males and females. The rate of lung cancer death to the whole of malignant diseases was 56.2% for males and 55.0% for females. Indoor soot and combustion emission derived from smoky coal produced in northern Fuyuan exhibited high mutagenic activities against Salmonella typhimurium TA98 strain in Ames test. Resected lung tissues derived from the patients with lung cancer in Fuyuan contained significantly higher concentrations of benzo(a)pyrene than those in Japan, both in males and females (i.e., 608.7 ± 477.1 pg/dry weight for samples of the patients in Fuyuan, 180.1 ± 104.5 for Japanese non-smokers, and 207.5 ± 98.8 for Japanese heavy smokers, respectively). These results suggest that mutagenic chemicals contained in coal as well as indoor environment may have a great influence on lung carcinogenesis in Fuyuan, Yunnan Province, China.

Key words: Lung cancer, carcinogenesis, carcinogen, environment, benzo(a)pyrene, coal.
str. 69-72

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