Zoledronic acid combined with adjuvant endocrine therapy of tamoxifen versus anastrozol plus ovarian function suppression in premenopausal early breast cancer: final analysis of the Austrian Breast and Colorectal Cancer Study Group Trial 12.

BACKGROUND: Zoledronic acid (ZOL) plus adjuvant endocrine therapy significantly improved disease-free survival (DFS) at 48- and 62-month follow-up in the ABCSG-12 trial. We present efficacy results of a final additional analysis after 94.4 months. PATIENTS AND METHODS: Patients were premenopausal women who had undergone primary surgery for stage I/II estrogen-receptor-positive and/or progesterone-receptor-positive breast cancer with <10 positive lymph nodes, and were scheduled for standard goserelin therapy. All 1803 patients received goserelin (3.6 mg every 28 days) and were randomized to tamoxifen (20 mg/days) or anastrozole (1 mg/days), both with or without ZOL (4 mg every 6 months) for 3 years. The primary end point was DFS; recurrence-free survival and overall survival (OS) were secondary end points. RESULTS: After 94.4-month median follow-up (range, 0-114 months), relative risks of disease progression [hazard ratio (HR) = 0.77; 95% confidence interval (CI) 0.60-0.99; P = 0.042] and of death (HR = 0.66; 95% CI 0.43-1.02; P = 0.064) are still reduced by ZOL although no longer significant at the predefined significance level. Overall, 251 DFS events and 86 deaths were reported. Absolute risk reductions with ZOL were 3.4% for DFS and 2.2% for OS. There was no DFS difference between tamoxifen alone versus anastrozole alone, but there was a pronounced higher risk of death for anastrozole-treated patients (HR = 1.63; 95% CI 1.05-1.45; P = 0.030). Treatments were generally well tolerated, with no reports of renal failure or osteonecrosis of the jaw. CONCLUSION: These final results from ABCSG 12 suggest that twice-yearly ZOL enhances the efficacy of adjuvant endocrine treatment, and this benefit is maintained long-term. CLINICALTRIALSGOV: NCT00295646 (http://www.clinicaltrials.gov/ct2/results?term=00295646).

Neutropenia management and granulocyte colony-stimulating factor use in patients with solid tumours receiving myelotoxic chemotherapy--findings from clinical practice.

PURPOSE: Clinical practice adherence to current guidelines that recommend primary prophylaxis (PP) with granulocyte colony-stimulating factors (G-CSFs) for patients at high (≥20 %) overall risk of febrile neutropenia (FN) was evaluated. METHODS: Adult patients with breast cancer, non-small cell lung cancer (NSCLC), small-cell lung cancer (SCLC), or ovarian cancer were enrolled if myelotoxic chemotherapy was planned, and they had an investigator-assessed overall FN risk ≥20 %. The primary outcome was FN incidence. RESULTS: In total, 1,347 patients were analysed (breast cancer, n = 829; NSCLC, n = 224; SCLC, n = 137; ovarian cancer, n = 157). Patients with breast cancer exhibited fewer individual FN risk factors than patients with other cancers and were far more likely to have received a high-FN-risk chemotherapy regimen. However, a substantial proportion of all patients (45-80 % across tumour types) did not receive G-CSF PP in alignment with investigator risk assessment and guideline recommendations. FN occurred in 127 patients overall (9 %, 95% confidence interval (CI) 8-11 %), and incidence was higher in SCLC (15 %) than other tumour types (8 % in ovarian and NSCLC, 9 % in breast cancer). A post hoc analysis of G-CSF use indicated that G-CSF prophylaxis was not given within the recommended timeframe after chemotherapy (within 1-3 days) or was not continued across all cycles in 39 % of patients. CONCLUSIONS: FN risk assessment was predominantly based on clinical judgement and individual risk factors, and guidelines regarding G-CSF PP for patients at high FN risk were not consistently followed. Improved education of physicians may enable more fully informed neutropenia management in patients with solid tumours.

Clonogenic growth in vitro: an independent biologic prognostic factor in ovarian carcinoma.

A retrospective analysis was performed to investigate the prognostic value of growth in a human tumor clonogenic assay system for 84 ovarian cancer patients. A significant difference in survival probability (determined by the method of Kaplan-Meier) was found by univariate analysis between patients with ovarian carcinoma whose tumors manifested clonogenic growth (defined as growth of greater than or equal to five colonies per plate) and patients whose tumors did not grow. Clonogenic growth in vitro was associated with worse prognosis (P = .007, log-rank test). A number of generally accepted prognostic factors, International Federation of Gynecology and Obstetrics (FIGO) stage (P = .003), residual tumor mass (P less than .001), and grade (P = .011), were also of prognostic importance in our patient population. Multivariate analysis, based on the Cox regression model, identified clonogenic growth as a significant independent prognostic parameter in ovarian carcinoma (P = .031), in addition to the conventional risk factors. Estimation of survival of individual patients was best accomplished by combining the factors of residual tumor mass (P less than .05), age (P less than .01), and clonogenic growth (P less than .05) (in sequence of decreasing potential of risk).

Lack of impact of platinum dose intensity on the outcome of ovarian cancer patients. 10-year results of a prospective randomised phase III study comparing carboplatin-cisplatin with cyclophosphamide-cisplatin.

This prospective multicentre phase III trial was conducted to assess whether increased platinum dose intensity (DI) by combining carboplatin with cisplatin has an impact on overall survival (OS) and progression-free interval (PFI) compared with the standard combination of cyclophosphamide and cisplatin in patients with epithelial ovarian cancer. A total of 253 patients with epithelial ovarian cancer of stages International Federation of Gynecology and Obstetrics (FIGO) IC-IV were randomised to receive either cyclophosphamide (600 mg/m(2), intravenously (i.v.), day 1) and cisplatin (100 mg/m(2), i.v., day 2) (n=125) as the standard regimen or carboplatin (300 mg/m(2), i.v., day 1) and cisplatin (100 mg/m(2), i.v., day 2) (n=128), every 28 days for six courses. The median follow-up was 6.0 years. 124 patients randomised to the platinum dose-intensified arm and 123 patients randomised to the standard arm met all of the eligibility criteria. Patient characteristics were well balanced between the two treatment groups. All eligible patients randomised were included in the analysis of OS and PFI. The median OS of the standard and platinum dose-intensified arms were 41.2 (95% Confidence Interval (CI): 29.2-50.7) and 43.0 months (95% CI: 34.3-63.2), respectively (P=Non-significant (N.S.). The median PFI in the standard arm was 29.7 (95% CI: 17.4-41.7) versus 23.1 months (95% CI: 17.8-35.4) in the platinum dose-intensified arm, respectively (P=N.S.). Toxicity, comprising leucopenia, granulocytopenia, thrombocytopenia, anaemia, emesis and nausea, was statistically significantly higher in the platinum dose-intensified arm than in the standard arm. Unexpectedly, no statistically significant differences were found between the 2 arms' overall neuro- and ototoxicity. When converting carboplatin-platinum into cisplatin-platinum on the basis of an equivalence ratio of 4:1, patients in the platinum dose-intensified arm received a total platinum dose 1.58 times the platinum dose of the standard arm. With 35.0 mg/m(2)/week being administered, the total platinum DI of the dose-intensified arm was statistically significantly (P<0.0001) higher than that of the standard regimen (with 22.0 mg/m(2) being administered). Calculating the average administered relative dose intensities of the regimens yielded almost identical results with 0.56 and 0.58 for the standard and experimental arms, respectively. Thus, by conventional means, a 1.6-fold increase in the platinum DI could be reached by combining carboplatin and cisplatin without unacceptable morbidity. Nevertheless, this did not translate into any therapeutic benefit for the patient, even in the optimally debulked group of patients for whom dose-intensification would have been expected to be of benefit.

Very low-dose adjuvant chemotherapy in steroid receptor negative stage I breast cancer patients. Austrian Breast Cancer Study Group.

A randomised clinical trial was performed to test whether or not low-dose chemotherapy lasting only 35 days improves the outcome of breast cancer patients with stage I disease and negative oestrogen and progesterone receptors (ER-, PgR-). Between 1984 and 1990, 277 stage I breast cancer patients with tumours negative for both oestrogen and progesterone receptors were randomised to receive either low-dose short-term chemotherapy or no chemotherapy. Chemotherapy consisted of one cycle of doxorubicin, vincristin (AV) and one cycle of cyclophosphamide, methotrexate, fluorouracil (CMF). Patients were stratified for tumour stage, type of surgery, menopausal status and participating centre. Results were analysed both by univariate and multivariate statistical. After a median length of follow-up of 84 months, disease-free (DFS) and overall survival (OS) did not differ significantly between patients having received adjuvant chemotherapy and the control group. Uni- and multivariate analysis did not show any significant prognostic or therapy related factor. A low-dose short-term adjuvant chemotherapy is insufficient to improve the prognosis of patients with breast cancer stage I with ER-, PgR-tumours.

Randomised phase II study of epirubicin-vindesine versus mitoxantrone-vindesine in metastatic breast cancer.

The purpose of this study was to compare the activity and toxicity of epirubicin-vindesine (EV) with mitoxantrone-vindesine (MV) in patients with metastatic breast cancer. A total of 295 patients was randomly allocated to treatment with vindesine 3 mg/m2 combined with either epirubicin 40 mg/m2 or mitoxantrone 10 mg/m2. All drugs were given by intravenous push, treatment cycles were repeated at 3-4 week intervals. 255 patients were available for response, and 283 for toxicity. EV and MV yielded similar objective response rates (34 and 26%, respectively), response durations, times to progression and survival. Median time to remission was 1.8 and 3.1 months (P = 0.006) with EV and MV, respectively. In patients with visceral metastases, response rate was higher with EV than MV (40 versus 23%; P = 0.03). Patients receiving MV had less nausea/vomiting (P = 0.007) and alopecia (P = < 0.001) of WHO grade > or = 2. Bone marrow, cardiac and other toxicities were mild with both treatments. The observed differences in activity and toxicity between the two regimens appear to have clinical relevance. EV proved to be more active in visceral disease and to be able to induce remissions more rapidly. Accordingly, patients with visceral metastases or severe tumour-related symptoms may benefit from epirubicin-based treatment. Subjective toxicities, i.e. nausea/vomiting and alopecia, were less frequent and severe with MV. Thus, MV may prove useful in patients with more indolent disease and appears to warrant phase III evaluation in such patients.

Analysis of factors influencing clonogenic growth in vitro of cells from ovarian carcinoma patients.

Clonogenic growth (defined as the formation of greater than or equal to 5 colonies per 5 x 10(5) viable nucleated cells per plate) of ovarian cancer specimens assessed in our clonogenic assay system was significantly associated with the proportion of tumor cells in the suspensions plated (N = 87; P = 0.0006), although there was no quantitative relationship with the corresponding plating efficiencies. An inverse correlation was observed between monocytes/macrophages/mesothelial cells (M) proportion and clonogenic growth (P = 0.013). These associations were most evident when only effusions were considered. Univariate analyses identified tumor cell content, M proportion and, to a lesser degree, granulocyte content as the only factors out of 12 examined to be correlated with colony formation. Multivariate analysis using a logistic regression model identified the proportion of tumor cells as the only significant factor predicting clonogenic growth in vitro (P = 0.0006). The overall accuracy of prediction for growth or non-growth was 63.2%.

Prediction of toxicity but not of clinical course by determining carboplatin exposure in patients with epithelial ovarian cancer treated with a combination of carboplatin and cisplatin.

We present the data from 105 patients with primary epithelial ovarian cancer, who received up to 6 cycles of carboplatin (300 mg/m2) and cisplatin (100 mg/m2) as one treatment arm of a prospective randomized trial. Values for first-course carboplatin area-under-the-curve (AUC) were determined retrospectively. WHO grade 3-4 thrombocytopenia was found in 10% of patients with low AUC (AUC <4 mg/ml x min), but in 44.6% of patients with high AUC (AUC 4 mg/ml x min) (chi-square p<0.0001). No single case of ototoxicity was found in the low AUC group but in 12% of patients in the high AUC group (chi-square p=0.003). Determination of carboplatin AUC may prevent ototoxicity and severe thrombocytopenia for the first cycle of combined treatment with carboplatin and cisplatin.

Influence of delayed staging laparotomy after laparoscopic removal of ovarian masses later found malignant.

OBJECTIVE: To determine whether delayed laparotomy after attempted laparoscopic excision of an ovarian mass later found to be malignant has an impact on the stage of disease. METHODS: A questionnaire regarding laparoscopic management of ovarian masses later found to be malignant was mailed to all gynecologic departments in Austria. Of the 70 cases reported, laparotomy was performed after laparoscopy in 48 cases. In 24 of these cases, laparotomy was performed within 17 days of laparoscopy, whereas 24 cases involved a delay of more than 17 days. Twenty-two patients in whom laparotomy was performed immediately after laparoscopy were used as controls. RESULTS: In patients with borderline tumors who underwent laparotomy more than 17 days after laparoscopy, the odds ratio (OR) for International Federation of Gynecology and Obstetrics (FIGO) stage IIB-IV disease was 5.3 (95% confidence interval [CI] 0.40, infinity), compared with patients undergoing immediate laparotomy (multivariate analysis). Patients with invasive ovarian cancer who underwent laparotomy more than 17 days after laparoscopy had an OR of 9.2 (CI 0.92, 481) for stage IIB-IV disease compared with patients undergoing immediate laparotomy (multivariate analysis). In patients with borderline tumors, multivariate analysis showed that the timing of laparotomy is an independent prognostic factor for the stage of disease. In invasive ovarian cancer, none of the factors evaluated by multivariate analysis was found to be an independent prognostic factor for the distribution of disease stage. A delay between laparoscopy and laparotomy may affect adversely the distribution of disease stage. CONCLUSION: The timing of subsequent laparotomy was found to be a factor predictive of the distribution of disease stage.

Preoperative CA 125: an independent prognostic factor in patients with stage I epithelial ovarian cancer.

OBJECTIVE: To evaluate the prognostic importance of preoperative CA 125 levels in patients with International Federation of Gynecology and Obstetrics (FIGO) stage I epithelial ovarian cancer in comparison with the established prognostic factors: degree of differentiation, FIGO substage, and age. METHODS: In a retrospective analysis, the traditional prognostic factors and CA125 levels (cutoff value 65 U/mL) were studied in 201 patients who were treated in five centers during 1984-1993. Patients with borderline tumors or non-epithelial ovarian carcinomas were excluded, as were women in whom CA 125 had not been determined preoperatively. RESULTS: In univariate analysis (Mantel test), overall survival decreased significantly in patients positive for CA 125 (P < .001). Substage (P = .004) and histologic grade (P = .01) also significantly influenced survival prognosis. When the effects of preoperative CA 125 levels were correlated with histologic grade, all three subgroups with CA 125 levels equal to or greater than 65 U/mL were associated with a decreased survival probability (grade 1, P = .04; grade 2, P = .003; grade 3, P = .01). Multivariate analysis (Cox model) identified preoperative CA 125 as the most powerful prognostic factor for survival (P < .001), the risk of dying of disease being 6.37 times higher (95% confidence interval 2.39-16.97) in CA 125-positive patients. Although FIGO substage retained its significant influence on survival (P = .03), histologic grade and age were not prognostically important. CONCLUSION: Randomized trials investigating the efficacy of adjuvant treatment in patients with FIGO stage I epithelial ovarian cancer should also include stratification by preoperative CA 125 levels.

The role of chemotherapy including ifosfamide for ovarian carcinoma. Austrian Collab. Ovarian Cancer Study Group.

On the basis of the results of earlier studies, 30 departments of gynecology have been cooperating nationwide in Austria since 1980 to promote the use of adjuvant chemotherapy after surgery for cure of ovarian carcinoma in early stages and the role of lymph node dissection and of second-look operation. Results recorded in more than 160 patients treated with adjuvant chemotherapy after so-called radical surgery performed in disease stages I and II demonstrate that only highly differentiated tumours in stage Ia can be cured by surgery only with no further adjuvant treatment. This underlines the necessity for staging. More than 200 patients with TNM stages III and IV were randomized after debulking surgery to receive treatment with different kinds of drug combinations to compare the therapeutic efficacy of a sequential alternating drug regimen consisting of Adriamycin-cisplatin + vincristine-cyclophosphamide + high-dose methotrexate with that of the combination of Adriamycin-cyclophosphamide and that of Adriamycin-cisplatin. High-dosed ifosfamide was also used in pilot studies.

Significance of pretreatment serum hemoglobin and survival in epithelial ovarian cancer.

Tumor anemia is common in patients with malignant tumors and it was repeatedly demonstrated to be associated with impaired prognosis in patients with malignant tumors. We conducted a retrospective analysis based on 553 patients with histologically proven epithelial ovarian cancer. Blood hemoglobin levels were determined before surgery and patients with values <12 g/dl were considered anemic. Data analysis included univariate and multiple Cox models. Tumor anemia was present in 143 (25.9%) patients before surgery. Tumor anemia was present in 143 (25.9%) patients before surgery. In a multivariate Cox model, pretreatment hemoglobin values proved to be an independent prognostic factor for patients with stage I-II epithelial ovarian cancer (n=203), but failed to attain significance in patients with stage III-IV disease (n=350). Tumor anemia defined as pretreatment hemoglobin values <12 g/dl may indicate patients with stage I and II epithelial ovarian cancer, who are at increased risk of relapse.

First report of lymphatic mapping with isosulfan blue dye and sentinel node biopsy in cervical cancer.

BACKGROUND: Sentinel lymph node status provides important information about the status of the regional nodes in various malignant tumors. Our report describes a method of identifying the sentinel lymph nodes in cervical cancer. PATIENTS AND METHODS: In three cases of early cervical cancer, isosulfan blue dye was injected paracervically into each lateral fornix immediately before surgery. RESULTS: In all cases we identified two to three blue stained (sentinel) lymph nodes located either at the iliac artery or in the obturatory space. The blue colored nodes were positive for disease, all other pelvic lymph nodes removed were negative. CONCLUSIONS: Our findings demonstrate that preoperative lymphatic mapping with vital blue dye is an easy to perform technique to visualize sentinel lymph nodes in cervical cancer. Sentinel lymph node status may be representative of the pelvic lymph node status in cervical cancer and thus could provide important information for further treatment.

TATI (tumor associated trypsin inhibitor) and cancer antigen 125 (CA 125) in patients with early-stage endometrial cancer.

BACKGROUND: In patients with gynecologic malignancies, a 6 kD polypeptide known as the tumor-associated trypsin inhibitor (TATI) is present in high concentrations, both in the urine and the serum. This study attempts to evaluate the usefulness of pretreatment serum levels of TATI (cutoff level 21 ng ml-1) and CA 125 (cutoff levels 35 U ml-1 and 65 U ml-1) in the prediction of early endometrial cancer. PATIENTS AND METHODS: One hundred twenty-seven patients with stage I and II endometrial carcinomas, 110 healthy women and 258 women with benign pelvic pathologies were evaluated. The data obtained were correlated with the tumor stage and tumor grade. RESULTS: Overall, TATI showed a sensitivity of 31% and a specificity of 81%. The sensitivity and specificity of CA 125 > 35 U ml-1 was 25% and 86%, respectively. When both serum tumor markers were combined the sensitivity increased to 48% (CA 125 > 35 U ml-1), with a specificity of 71%. A correlation with the depth of myometrial infiltration was found for neither of the tumor markers under investigation. In addition, neither TATI nor CA 125 correlated well with tumor grade. The combination of TATI and CA 125 had a high positive predictive value (84%) when no other gynecologic pathologies were present. Furthermore, if TATI and CA 125 levels are within normal ranges and gynecological examination does not show other abnormalities besides vaginal bleeding, endometrial carcinoma appears to be very unlikely. CONCLUSION: We concluded that, while TATI and CA 125 may not be recommended as a screening method for the detection of endometrial cancer, the combination of TATI and CA 125 is a valuable additional tool for further evaluation of women with suspected uterine cancer.

Does long-term application of granulocyte colony-stimulating factor adversely influence overall survival in patients with ovarian cancer? A clinical study.

The purpose of this study was to investigate the effect of long-term administration of G-CSF with regard to its impact on overall survival of patients with ovarian cancer. We report the results of a non-randomized trial on 64 patients with advanced ovarian cancer treated with 6 cycles of conventional chemotherapy. Chemotherapy comprised carboplatin 400 mg/m2 and epirubicin 70 mg/m2 on day 1 of each cycle and prednimustine 100 mg/m2 on days 3 to 7, every 28 days. Thirty-three patients received CEP chemotherapy with G-CSF support whereas 31 women received CEP chemotherapy alone. The schedule of G-CSF was 5 mg/kg/day subcutanously on days 8 to 21 of each cycle. The severity of reduction in white cells and neutrophil count was significantly different in the two treatment groups (p<0.05), with more toxicity in the non- G-CSF group. G-CSF users had a non significant 0.88-fold lower risk of dying from ovarian cancer (95% CI, 0.48-1.60, p=0.678). In a survival analysis using a Cox proportional hazards model, residual tumor remained as an independent prognostic factor. The increasing amount of residual tumor resulted in a 1.767-fold higher risk (95% CI, 1.23-2.53, p=0.002) of death secondary to the underlying disease. In conclusion, this trial has failed to demonstrate any negative impact on patients' overall survival for the additional use of G-CSF with platinum-based chemotherapy; our results were consistent with the beneficial effects of G-CSF treatment on cytotoxic chemotherapy-induced myelosuppression.

EGFR and steroid receptors in ovarian carcinoma: comparison with prognostic parameters and outcome of patients.

Epidermal growth factor receptor (EGFR), progesterone receptor (PR) and estrogen receptor (ER) status were analyzed in 108 primary ovarian epithelial carcinoma specimens. Receptor concentration was determined with radioligand binding assays. 61% of the carcinomas investigated were positive for EGFR, 29% for PR and 57% for ER. EGFR status was not correlated with histological grading of tumors and no difference in EGFR positivity was found between subgroups of ovarian carcinomas. On the other hand, 50% of the tumors with FIGO stage III and IV and tumors which could not be operated to be free of residual tumor mass were EGFR positive, whereas only 30% were positive within the group of tumors with FIGO stage I and II and no residual tumor mass. The outcome of the carcinoma patients was followed up for a maximum of 100 months. A significant correlation between EGFR positivity and a shorter progressive-free period as well as shorter overall survival was found. For PR and ER status no relation to patient survival became evident. The response to chemotherapy was significantly correlated to EGFR status. After 5 years 63% of the patients with negative versus 25% with positive EGFR were still alive indicating the impaired response of EGFR positive carcinomas to chemotherapy containing platinum compounds.

pS2 protein status fails to be an independent prognostic factor in an average breast cancer population.

In this study we analysed the cytosolic concentrations of the estrogen-regulated protein pS2 in tumors of 462 breast cancer patients, 16 benign breast tumors and 58 metastases. The median pS2 values were highest in breast cancer, followed by benign tumors and metastases (Kruskal-Wallis Test: p < 0.05). Information on other prognostic factors and clinical outcome was available for 354 patients (median follow-up, 35 months). We found a pS2 value of 2 ng/mg protein to be the best cut-off level to discriminate between pS2+ (63%) and pS2- (37%) tumors with respect to relapse-free survival (RFS) and overall survival (OS). The pS2 status was significantly correlated with age, estrogen receptor (ER) and progesterone receptor (PR) status. pS2 was negatively correlated with grading and was more often positive in invasive lobular than in invasive ductal carcinomas. ER, pS2 and grading were highly significantly correlated with each other. In univariate analysis pS2- patients showed a significantly shorter RFS (p = 0.0001) and OS (p = 0.0005). However, multiple regression analysis revealed that in our series of patients the pS2 status provides no independent prognostic information.

Influence of delayed diagnosis on established prognostic factors in endometrial cancer.

To evaluate the influence of delayed diagnosis on prognostic factors in endometrial cancer, we conducted a retrospective chart analysis based on the data of 116 postmenopausal patients with FIGO stage I-IV endometrial carcinoma. The interval from the first episode of post-menopausal vaginal bleeding to definitive, histological diagnosis (bleeding interval) was compared with tumor stage and various histomorphologic features in endometrial cancer. The mean bleeding interval was 12.7 +/- 17.8 weeks in 74 patients with FIGO stage IA, IB endometrial carcinoma and 35.2 +/- 69.3 weeks in 42 patients with stage IC-IV disease (t-test, p: 0.011). FIGO stage IA, IB disease was diagnosed in 23/26 (88%) patients with a bleeding interval <4 weeks, and in 22/34 (64%) and 29/56 (51%) patients with bleeding intervals of 4-8 weeks and >8 weeks, respectively (Chi-square 10.358, p=0.006). The correlation with histologic grade, lymph-node status, vessel invasion and histologic subtypes did not reach statistical significance. Our data confirm the clinical impression that postmenopausal vaginal bleeding is an early symptom in patients with endometrial cancer, and that advanced disease in the majority of cases might come from delayed diagnosis in women with poor compliance.

The influence of obesity on the disease-free survival in primary breast cancer.

Hyper-estrogenism is more common in obese than in non-obese women. Consequently obesity has been shown to increase the risk of hormone department tumors. Some investigators have claimed that obesity at the time of primary treatment may be an independent prognostic factor for breast cancer, but this issue is still controversial. Therefore, we conducted a retrospective analysis to assess the influence of obesity at the time of primary treatment on disease-free survival (DFS). Obesity was defined as an excess of more than 25% of ideal weight according to Broca's index ([Height (cm) -100])-10%). The Cox-model was used for multivariate analysis. Mean follow-up was 61 (range 6-126) months. 295 (62.3%) patients were classified as of normal weight and 178 (37.6%) as obese. Mean excess of ideal weight was 8.9 kilograms (kg) in premenopausal and 13.9 kg in postmenopausal patients (non-parametric t-test p < 0.00001). Patients with tumor size < 20mm, 20-50mm and > 50mm had a means excess of the real weight of 10.6kg, 12.5kg and 16.1kg, respectively (non-parametric t-test p < 0.0001). Percentual excess of real weight compared to ideal weight was 22.4 [+/-21.2] kg in patients without recurrence and 21.5 [+/-21.9] in patients with recurrent disease (nonparametric t-test p = 0.7256). Univariate analysis revealed no significant association between obesity and the DFS. Multivariate analysis identified axillary lymph node involvement as the only statistically significant prognostic factor for disease-free survival (RR 1.55; 95%-confidence interval 1.02-2.36; p:0.0368). Because of the high correlations and node-status, tumor size and histological grading, the other factors failed to be prognostically relevant in this analysis. Obesity was not found to influence DFS of patients with primary breast cancer and is therefore unlikely to constitute an independent prognostic factor. It may, however, contribute to delayed diagnosis, since a significant proportion of obese patients were diagnosed with local advanced disease.

The application of fibrin glue after axillary lymphadenectomy in the surgical treatment of human breast cancer.

Experimental studies point out that a reduction of lymph flow can be obtained by the local application of fibrin glue following axillary lymphadenectomy in the surgical treatment of breast cancer. In a prospective study the influence of human fibrin glue on postoperative axillary lymph secretion and the period of drainage of the wound cavity were evaluated. In 40 patients, 5 ml of fibrin glue (Tissucol) was applied to the wound cavity by the use of a spray applicator (Tissumat) immediately after axillary dissection of the lymph nodes. For drainage of the wound area Redon suction-drains were used. The daily amount of postoperative lymph secretion was measured and drains were removed at a lymph secretion of less than 20 ml. 40 patients who underwent surgery and axillary lymphadenectomy without subsequent application of fibrin glue sourced as control group. No significant difference concerning the total amount of lymph secretion, the mean period of drainage or the incidence of lymphatic cysts was observed. In our study, the expected occlusion of the wound cavity by the application of fibrin glue after axillary lymphadenectomy did not lead to any advantage when compared with the control group.