Ursula Denison

Oestrogen and progesterone receptor content as a prognostic factor in advanced epithelial ovarian carcinoma

Summary. Levels of oestrogen receptor (ER) and progesterone receptor (PgR) in ovarian cancer tissue were examined with regard to their prognostic importance for survival in 179 patients with primary epithelial ovarian cancer stage III or IV in relation to: FIGO‐stage, histological type, histological grade, age, ascites, and postoperative residual tumour. Hormone receptor content was determined with the DCC‐method, receptor values higher than 9 fmol/mg protein were considered positive. Response to postoperative chemotherapy was significantly correlated with PgR content (80% responders in the group with PgR positive tumours and only 61% responders in the group with PgR negative tumours). A Cox proportional hazards regression model identified histological grade, residual tumour, age and PgR content as independent prognostic factors for survival in advanced epithelial ovarian carcinoma. PgR content had particularly significant prognostic relevance for patients with postoperative residual tumour mass ≤2 cm in diameter. Within this group of patients, those who are PgR positive have a 2‐years survival probability of 83% compared with only 51% in the Pg R‐negative group.

Lunar phases and survival of breast cancer patients – a statistical analysis of 3,757 cases

The potential influence of lunar phases on human life has been widely discussed by the lay press. The purpose of this study was to find out whether the timing of surgery during particular lunar phases influences the survival of breast cancer patients. It has been postulated that breast cancer surgery performed during the waxing moon, or particularly at full moon, is associated with a poorer outcome. We tested this hypothesis by evaluating the overall survival for 3,757 consecutive patients with invasive breast cancer. All patients underwent either modified radical mastectomy or breast conserving surgery plus radiotherapy, followed by adjuvant cytotoxic or hormonal therapy. The date of definitive surgery was allocated to the lunar phases. 1,904 (50.7%) patients were operated on during the waxing moon and 1,853 (47.3%) during the waning moon. The median follow-up was 74 months (range 1–372 months). The mean age at primary surgery did not differ significantly in the two groups 58.39 (SD 13.14) versus 58.34 (12.75) (p > 0.05, t-test). Breast cancer stages at initial diagnosis were evenly distributed according to the lunar phases (p = 0.325; chi-square). Survival curves were plotted according to the method of Kaplan–Meier. No significant differences were observed when timing of surgery was allocated to the lunar phases (p = 0.4841, log-rank). Subgroup analysis of premenopausal patients revealed similar results (p = 0.2950, log-rank; n = 1072). Using multivariate Cox modelling, we found a significant association between the patients age, stage of disease and survival, whereas no association with survival was observed for the timing of surgery (RR = 1.062; 95% CI, 0.970–1.163; p = 0.1937). No significant differences in overall survival of breast cancer patients were observed when timing of breast cancer surgery during the lunar cycle was considered. Although this was not a prospective randomized trial, the statistical magnitude of the results do not support any recommendations for scheduling patients for surgery at any particular day of the lunar phase.

Anemia Is a Significant Prognostic Factor in Local Relapse-Free Survival of Premenopausal Primary Breast Cancer Patients Receiving Adjuvant Cyclophosphamide/Methotrexate/5-Fluorouracil Chemotherapy

Purpose: To determine the effects of anemia on local relapse-free, relapse-free, and overall survival (LRFS, RFS, and OS, respectively) in premenopausal, primary breast cancer patients receiving adjuvant polychemotherapy, and to determine which conventional prognostic factors affected these outcomes. Experimental Design: Four hundred twenty-four premenopausal patients with early-stage primary breast cancer and hormone receptor–expressing tumors were treated with i.v. cyclophosphamide/methotrexate/5-fluorouracil (CMF) polychemotherapy as part of an adjuvant phase III trial (Austrian Breast and Colorectal Cancer Study Group Trial 5). The influence of anemia (hemoglobin <12 g/dL) on LRFS, RFS, and OS was evaluated in a retrospective analysis. Results: Of 424 patients, 77 (18.2%) developed anemia on CMF chemotherapy. After a median follow-up time of 5 years, 8.9% of nonanemic patients had local relapse compared with 19.6% of anemic patients (P = 0.0006). Although mastectomy was associated with anemia (26% versus 13.7% in breast conserving surgery; P = 0.002), multivariate analysis did not show mastectomy per se to be a significant risk factor for LRFS. Age, lymph node status, and hemoglobin had an independent significant influence on LRFS (P < 0.005). Anemic patients had a relative risk of 2.96 (95% confidence interval, 1.41-6.23) for developing local relapse in comparison with nonanemic patients. Conclusion: Premenopausal breast cancer patients who developed anemia during the CMF regimen had significantly worse LRFS. In Austrian Breast and Colorectal Cancer Study Group Trial 5, anemia may have contributed to an almost doubled incidence of local recurrence in the chemotherapy arm. Molecular targets associated with tumor hypoxia and distinct from erythropoiesis should receive further attention in experimental and clinical settings.

Incidence of anaemia in breast cancer patients receiving adjuvant chemotherapy

Anaemia is frequent in breast cancer patients but often remains undiagnosed and untreated. To determine the incidence of anaemia a prospective survey of primary non-metastatic breast cancer patients who received at least four cycles of adjuvant, non-platinum multi-agent chemotherapy was conducted at 47 centres in Austria. Two hundred and forty seven patients were prospectively included between October 1999 and December 1999. Haemoglobin (Hb) levels were determined after surgery and prior to each cycle of chemotherapy. Treatment of anaemia (blood transfusion or epoetin alfa) during the observation period was at the physicians discretion. For the purpose of this study, patients were considered to be anaemic if their Hb was below 12 g/dl. At baseline (after surgery and before the first cycle of chemotherapy), 28.7% of all patients were anaemic. The only significant differentiating factor was the type of surgery. 37.9% of patients who underwent mastectomy were anaemic, whereas only 22.8% of patients who underwent breast conserving surgery were anaemic. Forty two percent of 176 patients with a Hb level of ≥12 g/dl at baseline developed anaemia during adjuvant chemotherapy. The only factor that significantly influenced the development of anaemia during chemotherapy was the Hb level at baseline. The total incidence of anaemia in patients with primary breast cancer who underwent surgery followed by adjuvant multi-agent chemotherapy was 58.7%. Forty nine patients (20.2%), 48 patients (19.2%) and 48 patients (19.2%) showed a decrease in Hb levels by 1 g/dl, 1–2 g/dl and >2 g/dl, respectively. Only 18.6% of the patients who were found to be anaemic received anaemia treatment. The two most important factors for developing anaemia are the kind of surgery and the Hb level prior to chemotherapy.

Prognostic factors related to recurrent endometrial carcinoma following initial surgery

Site of recurrence and histological type are significant prognostic factors for survival in recurrent endometrial carcinoma.

Impact of haemoglobin levels during adjuvant chemotherapy on the survival of patients with primary breast cancer

Tumour anaemia is a common symptom in cancer patients, particularly in those receiving chemotherapy. The aim of the current study was to analyse the impact of haemoglobin levels on the prognosis of patients with primary breast cancer receiving adjuvant chemotherapy. A total of 129 patients were available for analysis. The estimated median five-year overall survival rate was 76.6%. Mean Hb prior to primary surgery was 13.8 g/dl (SD 1.09), pre-chemotherapy Hb 12.8 g/dl (SD 1.2), and nadir Hb during chemotherapy 11.0 g/dl (SD1.1), respectively. Hb values were analysed as continuous variables in the Cox model. Survival analyses did not show a correlation between preoperative and pre-chemotherapy Hb levels with patient outcome. However, univariate analysis identified low nadir Hb (p=0.008), larger tumours (p=0.042), and hormone-receptor-negative tumours (p=0.022) to be significantly associated with poor patient survival. This result was persistent when analysis was adjusted for relevant prognostic factors in a multivariate Cox proportional hazards model. Nadir Hb, 1.54-fold increased risk for death (95% CI 1.03–2.32), and tumour size, 3.2-fold increased risk (95% CI 1.17–8.77) remained as independent variables, whereas hormone-receptor status failed to retain significance. The present data showed anaemia during adjuvant chemotherapy to be associated with poor survival in patients with primary breast cancer. Prospective randomized trials are warranted to examine the value of correcting anaemia with regard to improve disease control and survival.

Is CA-125 monitoring useful in patients with epithelial ovarian carcinoma and preoperative negative CA-125 serum levels?

Between December 1983 and December 1988 we examined the postoperative tumor marker development and correlated this to the clinical course of the disease in 56 patients suffering from primary epithelial ovarian carcinoma of International Federation of Gynecology and Obstetrics stages I-III and with a preoperative CA-125 serum level less than or equal to 65 U/ml. In 54% of all cases there was a reduction of more than 50% of the CA-125 serum level within the first 3 months after surgery. Nine out of thirteen patients with progressive disease (69%) showed an increasing CA-125 serum level with a median lead time of 6 months (0-11 months) prior to clinical diagnosis. These preliminary results indicate that the monitoring of cancer patients with CA-125 tumor marker seems to be a useful method of early diagnosis of progressive disease even in patients with preoperative serum levels lower than 65 U/ml.

Femara®: der neue Aromatasehemmer

Ziel aller hormonellen Behandlungsmassnahmen ist die Ausschaltung der östrogenbedingten Wachstumsstimulation von Tumorzellen. Dies ist durch Suppression der Östrogenproduktion, durch Medikamente, die die Östrogenrezeptoren besetzen, ohne östrogene Wirkung auszuüben, und durch Reduktion der zellulären Östrogenrezeptoren möglich. Aromatasehemmer unterdrücken die zelluläre Umwandlung von Androstendion zu Östron. Androstendion wird in der Nebennierenrinde gebildet und kann in den peripheren Geweben, auch im Tumorgewebe, zu Östron umgewandelt werden. Dieser Stoffwechselweg stellt die Hauptquelle der Östrogenproduktion postmenopausaler Patientinnen dar. Die Gruppe der Aromatasehemmer hat während der letzten Jahre einen festen Platz in den Therapiekonzepten für Patientinnen mit hormonabhängigen, metastasierenden Mammakarzinomen einnehmen können. Neue Aromatasehemmer wie Letrozol oder Anastrozol lassen die Steroidsynthese in der Nebenniere weitgehend unbeeinflusst.

Einfluss einer adjuvanten Hormontherapie auf den Gesamtorganismus der Frau: Nutzen versus potentieller Schaden

Not only do patients suffering from hormone receptor-positive tumors of the mammary gland show an increased survival rate, but patients with endometrial as well as ovarian cancer also benefit from hormone replacement therapy. On the one hand, hormonal treatment as well as any other medical treatment influences the tumor, and on the other hand it influences the whole body, which sometimes leads to unfavorable events (increased rate of endometrial cancers during tamoxifen therapy vs. increase of bone density in postmenopausal women). Therefore, hormonal cancer treatment is often suspect. As unfavorable events are rare, and since the benefit is convincing, doctors have to inform women about all the pros and cons of this treatment option, which leads to well-informed and cooperative patients.

Prospective Randomized Trial of Sequential Alternating Chemotherapy in Advanced Ovarian Carcinoma

Background: The aim of this multicentric study was to compare the therapeutic efficacy of a sequentially alternating drug regimen consisting of adriamycin-cisplatinum (AP), vincristine-cyclophosphamid