Overexpression of cathepsin B correlates with angiogenesis in colon adenocarcinoma.

Some studies have shown the influence of proteases and vascular density in colorectal primary tumors on spreading and on the course of colorectal cancer. In the present study we have analyzed the relationships between overexpression of cathepsin B protein and angiogenesis intensity in resected colon tumors and their impact on prognosis. It has been investigated in a series of 90 colon cancer patients. Immunohistochemistry was used to evaluate cathepsin B overexpression in cancer cells and to visualize microvessels with antibodies against von Willebrand factor. Overexpression of cathepsin B was observed if more than 50% of cancer cells in searched field showed immunoreactivity with antibody against cathepsin B. Intensity of angiogenesis was evaluated as a mean number of microvessels from three fields with highest vessel number. In 36 cases (40%) overexpression of cathepsin B was detected. Increased angiogenesis (above median 31 vessels per 0.785 mm2) correlated positively with cathepsin B overexpression (p=0.0006). Higher vascular density associated with the presence of metastases in regional lymph nodes (p=0.01). Overexpression of cathepsin B was observed more often in group of older people (age above median 65 years; p=0.005). According to univariate analysis metastases in regional lymph nodes (p=0.0007), increased angiogenesis (p=0.0085), and distant metastases (p=0.02) were the features potentially influencing prognosis. Multivariate analysis revealed independent prognostic value only in case of metastases in regional lymph nodes (p=0.013) and when distant metastases were present (p=0.021), but not when increased angiogenesis in primary colon adenocarcinoma was observed (p=0.078). In conclusion we can say that there is a close relationship between intensity of angiogenesis and overexpression of cathepsin B protein in cancer cells in resected colon adenocarcinoma.

[Elevation of serum Ca 15-3 antigen: an early indicator of distant metastasis from breast cancer. Retrospective analysis of 733 cases]. / Wzrost stezenia antygenu CA 15-3 w surowicy--wczesny wskaznik przerzutów odleglych raka piersi: retrospektywna analiza 733 chorych.

UNLABELLED: Aim of study was to summarize six-year institutional experience with serial evaluation of circulating CA15-3 antigen as a method of early detection of breast cancer relapse. MATERIAL AND METHODS: CA15-3 concentrations were assayed immuno-enzymatically in the sera of 733 women with breast carcinoma: in 707 cases marker was analyzed serially (every 4 months during follow-up after completion of radical treatment and when the relapse of breast cancer was clinically suspected) and in 26 patients--at diagnosis of locoregional relapse and\or breast cancer dissemination; 5493 assays of the CA15-3 antigen were performed in total. The cut-off limit was established at 30 u/ml. Results of CA15-3 tests were analyzed in relation to clinical status of the disease and dominant site of breast cancer relapse. RESULTS: 1) in patients with distant metastases (N = 149), mean serum CA15-3 values and the percentage of positive results were significantly higher as compared to cases with locoregional relapse and carcinoma of the contralateral breast (N = 54; p < 0.0001) and those without clinical evidence of relapse (N = 530; p < 0.0001), in agreement with previous studies; 2) the highest mean values of CA15-3 were observed in patients with liver and multiple metastases, lower in those with bone or lung secondaries, and the lowest when the metastatic involvement of supraclavicular nodes was noticed; 3) the CA15-3 sensitivity rates were higher in patients with liver or bone metastases (91.7% and 91.4%, respectively), as compared to those with multiple (79.5%) and lung (72.4%) secondaries, and the lowest when metastases in supraclavicular nodes (40.0%) or other organs (60.0%) were diagnosed; 4) the comparison of subjects with liver secondaries and those with other sites of breast cancer dissemination indicated statistically significant difference in the mean CA15-3 values (p < 0.0001) and the number of positive results of the test (p < 0.05); 5) the sensitivity rates of CA15-3 antigen for one, two, three and more skeletal metastases detected by bone scintigraphy were 50%, 100% and 100%, respectively (N = 30); 6) in 84 out of 116 (72.4%) patients with distant metastases, the increased CA15-3 concentration preceded the clinical diagnosis of the relapse with the median lead time 9 months (range: 1-40); 7) the highest positivity rates of the lead time were observed in patients with liver or lung metastases (93.8% and 81.0%, respectively) and the lowest one in those with multiple sites of metastases (43.0%). CONCLUSION: The study confirmed the validity of serial CA15-3 assays in the early diagnosis of breast metastatic disease. It is worth to emphasize the high sensitivity of the CA15-3 test in detecting bone metastases (100% in patients with scintigraphically diagnosed two or more metastatic lesions), but the group of patients was too small to make our observation conclusive. In none of the studies published previously, the beneficial impact of serial CA15-3 assays during follow-up on survival and quality of life in breast cancer patients was clearly demonstrated. Thus, modifying treatment based solely on increasing marker levels is not recommended.

Endometrial cancer in patients with breast carcinoma treated with tamoxifen: report of two cases and the literature overview.

Tamoxifen (TAM) is the endocrine treatment of choice in the first-line therapy for all stages of breast cancer, in both pre- and postmenopausal women. Some clinical studies indicated a small but significant increase in the risk of subsequent endometrial carcinoma in breast cancer women who take TAM as an adjuvant therapy. In this study, we present two cases of breast cancer patients in whom endometrial cancer was diagnosed during TAM treatment; the current status of knowledge on the relationship between TAM use and the risk of endometrial cancer is reviewed.

Anthracycline-induced cardiotoxicity: clinical course, risk factors, pathogenesis, detection and prevention--review of the literature.

Anthracycline antibiotics are widely used antineoplastic agents and their efficacy for the treatment of various haemopoietic or solid tumours has been well established in clinical practice. Cardiotoxicity is one of the most serious side effects of anthracyclines. The risk of cumulative, life-threatening toxic cardiomyopathy limits their therapeutic potential. In this article, acute, subacute, chronic and late-onset cardiac function impairment associated with anthracycline administration has been characterised. The current views on the methods of detection, pathogenesis and prevention of such toxicity have been reviewed.

[Usefulness of CA 15-3 antigen determination for evaluation of response to second-line chemotherapy in patients with breast cancer: preliminary study]. / Przydatnosc oznaczania antygenu CA 15-3 w ocenie skutecznosci chemioterapii drugiego rzutu u chorych na raka sutka: doniesienie wstepne.

The aim of this study was to assess effects of second-line chemotherapy in metastatic breast cancer via determination of CA 15-3 marker. Analysis included 73 women, in whom distant metastases were diagnosed within 14-72 months (median: 43) after the completion of basic therapy. Average age of patients at primary diagnosis was 50.7 +/- 12.6 years. Dominant sites of metastases were: liver (27 patients) and lungs (24 patients). Serum CA 15-3 was examined immunoenzymatically at diagnosis of distant metastases and then after 2-4 cycles (median 4) of anthracycline-based chemotherapy. Changes of mean CA 15-3 values correlated with the UICC response criteria. There was a significant fall in mean levels of CA 15-3 after treatment in patients with complete (p < 0.004) and partial regression of metastatic lesions (p < 0.03). Stabilization and progression of the disease were associated with raise in CA 15-3 mean values, but the difference was significant only in the latter group (p < 0.02). In 31 out of 39 patients (79.5%) with regressive disease (complete and partial response) CA 15-3 levels decreased by at least 25% after treatment. Nine of 11 (81.8%) patients with stable disease had the antigen concentrations that did not vary by more than +/- 25% of the initial CA 15-3 value. CA 15-3 levels raised by at least 25% in 22 out of 23 (95.7%) cases with progressive breast cancer. Overall, CA 15-3 variations correlated with the disease status in 62 (84.9%) patients. These findings confirmed the usefulness of CA 15-3 determinations in evaluating the efficacy of second-line chemotherapy in patients with advanced breast cancer.

[Level of CA 15-3 antigen--a prognostic factor in patients with breast cancer?]. / Stezenie antygenu CA 15-3--czynnik rokowniczy u chorych na raka sutka?

Serum CA 15-3 concentrations were determined using sandwich enzyme immunoassay in 430 women: 214 breast cancer patients prior to any therapy, 161 patients with benign breast diseases, and 55 healthy controls; the cut-off limit was established at 30.0 U/ml. In breast cancer patients, CA 15-3 levels positively correlated with negative prognostic factors: higher tumor size (p < 0.001), positive axillary lymph nodes (p < 0.02), high histological grade (p < 0.01), low contents of estrogen (p < 0.05) and progesterone (p < 0.006) receptors. However serum CA 15-3 values raised in parallel with clinical stage of breast cancer, the difference was not significant. The overall diagnostic sensitivity and specificity of the test were 24.3% and 94.9%, respectively. The mean serum CA 15-3 values and the percentage of positive results in breast cancer patients were significantly higher as compared to benign breast diseases group (27.52 +/- 27.01 vs. 16.75 +/- 8.43, p < 0.001; 24.3% vs. 5.6%, p < 0.001, respectively) as well as to healthy controls (27.52 27.01 vs. 13.37 +/- 6.51, p < 0.001; 24.3% vs. 3.6%, p < 0.01, respectively). The sensitivity of the CA 15-3 test is low and thus not suitable for the differential diagnosis of breast lumps. Our data suggest potential prognostic value of pretreatment CA 15-3 assays in breast cancer patients.

Pretreatment values of serum CA 15-3 antigen related to prognostic factors in breast cancer patients.

In the present study results of serum CA 15-3 immunoassay obtained at diagnosis in 231 breast cancer women (average age: 54.6, range: 27-87 years) were correlated with prognostic factors of the disease; the cut-off level was established at 30.0 U/ ml. As a result, elevated mean values of serum CA 15-3 as well as positivity rates of the test were significantly associated with more advanced stage of breast cancer, presence of distant metastases, involvement of four and more axillary lymph nodes, high BLOOM and RICHARDSON grade [3], low contents of estrogen (ER) and progesterone (PgR) receptors. Although serum CA 15-3 concentrations should be paralleled the increasing tumor size, the difference being significant only for the proportion of positive results. Our findings suggest that pretreatment levels of CA 15-3 antigen represent the breast cancer extent and reflect the cell differentiation and aggressiveness of the tumor. We conclude that pretreatment concentrations of CA 15-3 antigen may be useful as a prognostic factor in breast cancer patients.

p53 expression in breast cancer related to prognostic factors.

In this article the results of molecular marker p53 examinations were presented in relation to the following established breast cancer prognostic factors: age, histologic type, histologic grade, lymph node involvement, tumor size as well as estrogen a progesterone receptor status. Twenty one percent of these primary breast cancer specimens exhibited the overexpression of p53 protein. Significant associations were found between p53 overexpression and younger age, high histologic grade and low content of estrogen and progesterone receptors. Identification of p53-positive breast carcinomas potentially represents a clinically useful indicator of breast cancer aggressiveness.

[Use of aminoglutethimide in the hormonal treatment of patients with advanced breast cancer]. / Zastosowanie aminoglutetymidu w hormonoterapii chorych z zaawansowanym rakiem sutka.

54 patients (pts) with metastatic breast cancer were treated with aminoglutethimide 250 mg p.o. twice a day with hydrocortisone 40 mg p.o./day. All pts were postmenopausal, mean age 63 years, and pretreated with cytostatics and/or hormones. Dominant sites of metastases were: soft tissues 29 pts. bone 12 pts. lungs 6 pts. Objective responses were: 4 (7.4%) CR, 15 (27.8%) PR, 16 (29.6%) NC and 19 (35.2%) PD (UICC criteria). The response (CR + PR) at metastatic sites was: soft tissues 12 (41%), bone 4 (33%). The mean response duration was 15.0 months for CR; 10.2 for PR and 5.5 months for NC. The results of the study confirm that low--dose aminoglutethimide is an effective second-line hormonal treatment of advanced breast cancer.

Evaluation of CA 15-3 tumor marker in the diagnosis of breast cancer. A pilot study.

Single determinations of serum CA 15-3 levels were performed by sandwich enzyme immunoassay in 160 women: 77 patients with nonmalignant breast tumors (64 had fibrocystic disease, 11 had fibroadenoma, 2 had intraductal papilloma) and 83 patients with primary breast cancer prior to any treatment; the cut-off limit was established at 30 U/ml. The overall diagnostic sensitivity and specificity of the CA 15-3 test was 19.3% and 94.8%, respectively. The positive and negative predictive values were 80.0% and 52.1%. The mean CA 15-3 value was significantly lower in patients with benign breast tumors as compared with the breast cancer group: 16.8 +/- 8.2 vs. 23.9 +/- 20.9 U/ml (p < 0.01) as well as the percentage of positive results of the test: 5.2% vs. 19.3% (p < 0.02). Serum CA 15-3 level in breast cancer patients correlated with: (1) clinical stage: a higher percentage of positive results was observed in patients with more advanced cancer: Stage I-0%, Stage II-10.6%, Stage III-29.6%, and Stage IV-100.0% according to UICC classification; the comparison of breast cancer patients with early stage of disease (I+II) and those with more advanced cancer (III+IV) revealed statistically significant (p < 0.01) difference in the mean serum CA 15-3 value (19.7 +/- 12.8 vs. 31.5 +/- 29.2 U/ml) as well as in the percentage of positive results (9.4% vs. 36.7%, p < 0.01); (2) the histological grading according to Bloom and Richardson: 5.41% of positivity was observed in low and intermediate grade cancers (I+II) vs. 66.7% in grade III (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Lipoprotein profile in breast cancer women: effect of tamoxifen treatment.

Electrophoretic lipoprotein analyses were performed in 51 patients on tamoxifen and compared with those obtained from 33 newly diagnosed breast cancer patients and with data from the group of healthy women. A statistically significant lower rate of dyslipoproteinemia has been demonstrated in tamoxifen group in comparison with untreated patients; 23.5% vs. 54.5% (p < 0.01). Comparing the results of the latter group with normal subjects there was a significantly higher frequency of dyslipoproteinemia in untreated patients, 54.5% vs. 28.9% (p < 0.05). Our findings confirmed an estrogen-like influence of tamoxifen on lipoprotein profile in postmenopausal breast cancer patients.

[Use of dexamethasone as an antiemetic in patients with breast cancer treated with the CMF regimen]. / Zastosowanie deksametazonu jako leku przeciwwymiotnego u chorych na raka sutka leczonych wg schematu CMF.

The antiemetic efficacy of dexamethasone (Dexaven) was examined in patients with breast cancer during chemotherapy CMF (cyclophosphamide, methotrexate and 5-fluorouracil) in comparison with patients treated identically but without dexamethasone. Comparison of the revealed statistically significant lower nausea incidence (p < 0.025) and lower vomiting incidence (p < 0.025) in the group of patients receiving dexamethasone. The results confirm value of dexamethasone as an effective and safe antiemetic agent using during chemotherapy CMF.

The effect of tamoxifen treatment on serum cholesterol fractions in breast cancer women.

Serum levels of total, free, HDL- and LDL-cholesterol were determined in 45 postmenopausal breast cancer women treated with tamoxifen (TAM) from 6 to 73 months (mean duration of TAM treatment was 21.3 months) as an adjuvant therapy after mastectomy, and in the control group of 33 breast cancer women at the time of diagnosis before any treatment. The mean age of patients was 63 years in the TAM treated group and 70 years in the untreated breast cancer patients. TAM treated patients were found to have significantly lower concentration of serum total cholesterol (5.43 mmol/l vs. 6.44 mmol/l; p < 0.02) and LDL-cholesterol (3.54 mmol/l vs. 4.32 mmol/l; p < 0.01). There were 8 (18%) hypercholesterolemic patients in the TAM treated group vs. 13 (39%) in the untreated breast cancer patients (p < 0.05). No statistically significant differences were observed in serum concentrations of free and HDL-cholesterol in the two evaluated groups. We conclude that the TAM-induced changes in serum lipid concentrations are due to an estrogen-like activity of the agent and the reduction of total and LDL-cholesterol level seems to be an additional advantage of TAM treatment.

[Level of total cholesterol in serum of patients with breast cancer treated with tamoxifen]. / Stezenie cholesterolu calkowitego w surowicy u chorych na raka sutka leczonych tamoksyfenem.

Estrogens play an important role in lipid metabolism regulation. The present study aimed at evaluating an effect of anti-estrogen therapy with tamoxifen on blood serum total cholesterol levels in women with breast cancer. Mean total cholesterol concentration in women treated with tamoxifen was 5.36 mmol/l vs. 6.64 mmol/l in patients not treated with tamoxifen. The difference was statistically significant (P < .001). Hypercholesterolemia was diagnosed only in 1 patient treated with tamoxifen (2.4%) while in 9 (27.35) patients not given this drug. The difference was also statistically significant (P < .001). Lower blood serum concentrations of the total cholesterol in women treated with tamoxifen are probably produced by the estrogen-like effect on lipid metabolism.