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In a large population-based case-control study in Germany, including 3,464 breast cancer cases aged 50-74 at diagnosis and 6,657 population based and frequency matched controls, we investigated the effects of menopausal hormone therapy (HT) by type, regimen, timing and progestagenic constituent on postmenopausal breast cancer risk overall and according to histological type. Data were collected by face-to-face interviews. Logistic and polytomous logistic regression analysis were used to estimate odds ratios (OR) and 95%-confidence intervals (95% CI). Risk of invasive breast cancer was significantly elevated in current users (OR, 1.73, 95% CI, 1.55-1.94) and heterogeneous by histological type (p < 0.01), being more than 2-fold higher for lobular and tubular than for ductal cancer. Risks for current users varied significantly by type and regimen of HT, with ORs per year of use of 1.05 (95% CI, 1.04-1.06) for continuous combined estrogen-progestagen, 1.03 (95% CI, 1.02-1.04) for cyclical EP and 1.01 (95% CI, 1.00-1.03) for estrogen-only therapy. No statistically significant increase in risk was observed after 5 years of cessation of HT use for any histological type. Analyses of progestagenic content by regimen revealed a significantly higher risk for continuously administered norethisterone- or levonorgestrel-derived progestagens than for continuously administered progesterone-derived progestagens (OR, 2.27, 95% CI, 1.98-2.62 vs. 1.47, 95% CI, 1.12-1.93, respectively, p = 0.003), which may be explained by dose rather than type of progestagen. These data suggest that the risks associated with menopausal HT differ by type and regimen of HT and histological type of breast cancer and may vary by progestagenic component, depending on the effective dose.

A retrospective analysis of 78 maternal deaths was performed during 1991-1992 to estimate maternal mortality at the maternity unit of the main tertiary level hospital in The Gambia. The non-abortion maternal mortality ratio (MMR) was 736 per 100 000 live births. Among the direct causes, haemorrhage caused most deaths (24%), followed by hypertensive disorders in pregnancy (HDP) (21%). Sepsis was the main cause of death in 15%. Anaemia led among the indirect causes of death (8%) and was a co-factor in 41% of all deaths. Substandard care factors other than medical causes were determined involving health care facilities, staff, drugs and equipment, and patient-related factors. Well known risk factors of low age (< or = 19 years) and nulliparity were highly represented in the maternal death group, and delivery by Caesarean section occurred more than threefold compared to the overall Caesarean section rate. Taking haemorrhage as an example, it is demonstrated that the way diagnoses are grouped significantly affects the statistical elaboration of maternal deaths.

This is a report on 278 patients who underwent subcutaneous mastectomy (SCM) at the Gynaecological Department of the University Hospital Heidelberg between 1980 and 1996. These operations were indicated either because of diagnostic problems (n = 104), a carcinoma of the contralateral breast (n = 33), non-invasive lobular carcinoma (n = 33), non-invasive ductal carcinoma (n=64), recurrent disease (n=8) or invasive carcinoma (n=36). In the group of patients with diagnostic problems occult lesions were found in 16%. In women with a previously known contralateral carcinoma occult carcinomata were diagnosed in 27%. In cases with a preoperative lobular carcinoma in situ we found ipsilaterally 6% occult invasive carcinoma and in 20% with a preoperatively diagnosed ductal carcinoma in situ. After a median follow up of 16.6 years the local recurrence rate for the invasive carcinoma was 19%, for LCIS was 10% and for DCIS was 3%. The recurrence free survival after 10 years was 91% for DCIS and LCIS and 86% for invasive carcinoma. The overall survival after ten years was 97% for DCIS, 95% for LCIS and 90% for invasive carcinoma. The incidence of invasive breast cancer after prophylactic subcutaneous mastectomy was 1 %. The findings of this study support the use of SCM because of comparable results in local recurrence rates and overall survival with breast conserving therapy and mastectomy, therefore SCM is a further therapeutic option.

Developing primary systemic chemotherapy (PST) regimens that induce higher pathological complete response (pCR) rates remains a challenge in operable breast cancer. We recruited 77 eligible patients into a multicentre phase I/II study to evaluate the maximum tolerated dose (MTD), toxicity and efficacy of preoperative gemcitabine day 1 and 8 (800 mg/m 2 fixed dose), epirubicin and docetaxel on day 1 (doses escalated from 60 mg/m 2 ) (GEDoc), repeated 3-weekly for 6 cycles with filgrastim support. MTD for epirubicin was 90 mg/m 2 and for docetaxel 75 mg/m 2 . Dose-limiting toxicities (DLTs) included febrile neutropenia and grade 3 diarrhoea. Clinical response rate was 92%, pCR rate was 26%. 79% of patients had breast-conserving surgery. Grade 3/4 leucopenia was the main toxicity, occurring in 55 (87%) of 63 patients treated at the MTD. Non-haematological toxicity caused no serious clinical problems. In conclusion, GEDoc is highly active as PST. Efficacy and toxicity compare favourably with other effective combinations.

Purpose: The 6th edition of TNM classification, valid since January 1, 2003, shows important changes in breast cancer classification, especially regarding lymph node status and UICC stage grouping. The effects of the redefinition of the TNM categories on stage and prognosis have not yet been studied in a large cohort of patients. Patients and Methods: We analyzed TNM staging of 5366 breast cancer cases registered at the Gynecological University Hospital Heidelberg (diagnosed from 1985 to 2000) according to the old and the new TNM classification. The effects of the new classification system were examined with regard to stage grouping and survival. Results: One of the most important effects of the 6th TNM edition is that reclassification of patients with nodal stage pN1 (5th edition) are now graded in the new nodal categories pN1, pN2 or pN3 according to the number and the localization of lymph node metastasis. This shifting of cases significantly increases the number of patients in UICC Stage III. Thereby, relative survival rates in the new pN categories 1, 2 and 3 and in the new UICC Stages II and III are visibly improved (so called Will Rogers Phenomenon or stage migration). Apart from that, splitting of the big group of patients with nodal stage pN1 (5th edition) provides a prognostically more meaningful stratification of patients, permitting easier identification of prognostically unfavorable cases. A new division of cases also resulted for patients with nodal stage pN2 (5th edition) according to the number of affected lymph nodes, permitting a better identification of prognostically - more favorable cases in this group. Conclusion: Prognostic data that relate to the 5th edition ofTNM and the tumor stages defined therein are not directly comparable with the 6th edition of TNM. This should be considered when analyzing clinical studies using the new staging system.

Purpose: Neoadjuvant chemotherapy (pCHT) is an established method to reduce tumor size (downstaging) in breast cancer patients before performing breast conserving therapy. The consequences of pCHT on tumor cell dissemination (TCD) in these patients are not known. The aim of this study was to evaluate tumor cell dissemination before and after pCHT in breast cancer patients. In addition, the prognostic value of TCD after pCHT was studied. Patients and Methods: 140 women with non-inflammatory, locally advanced breast cancer (tumor size > 3 cm and an unfavorable relation between breast and tumor size) received neoadjuvant chemotherapy with Epirubicin/Cyclophosphamide (90/ 600 mg/m 2 every 3 weeks for 4 cycles). In all patients bilateral aspiration of bone marrow was performed at the time of surgery (after neoadjuvant chemotherapy). In 42 of the 140 patients additional bone marrow aspirations were taken before neoadjuvant chemotherapy. Results: 68 of 140(49%) breast cancer patients had disseminated tumor cells (TCD) after neoadjuvant chemotherapy. TCD was an independent prognostic factor for disease free intervals (p=0.022, RR=2.63) and overall survival (p=0.032, RR=2.23). 20 of 42 patients had disseminated tumor cells before and after neoadjuvant chemotherapy. In contrast, 18 patients had no tumor cell dissemination during neoadjuvant treatment. Four patients had a change of their bone marrow status. Conclusion: Our results demonstrate that TCD is not influenced by neoadjuvant chemotherapy and remains an independent prognostic factor after pCHT. However, future studies will need to investigate whether neoadjuvant therapy changes the metastatic behaviour of TCD.

Ovarian cancer during pregnancy is rare. We report on a 35-year-old para 3 who showed ascites after an uncomplicated pregnancy and delivery. Sonography showed ovarian masses suspicious for malignancy. Laparotomy confirmed FIGO stage IIIC ovarian cancer. Tumor debulking was performed and combination platinum-based chemotherapy was initiated. We review the diagnostic features and role of ultrasonography in women with possible ovarian cancer during pregnancy.

Follow-up for patients with breast and genital cancers is part of the overall cancer care. Relevant data about early detection, diagnostic procedures and therapies in the adjuvant and palliative setting are available. Information about the value of and the strategies for time intervals and diagnostic procedures during the follow-up interval are up to date not standardized. Large scale data from prospective randomised trials or evidence-based criteria are missing for most procedures applied. As a consequence a clinically orientated follow-up care programme is proposed. This programme encompasses individualisation of care with an informative, detailed and structured talk and a clinically directed exam. The detection of clinical signs and symptoms leads to further diagnostic procedures. 'Talking Care' is the way of personal care for the diseased women. Follow-up care is divided into a general and a specific part. The latter summarizes organ-specific symptoms, frequencies and nature of exams. Early cancer detection for other cancer types has to be integrated. These standards are the summary of the available and evident study data, clinical experiences, the wishes and the demands of the patients and the integration of factors for quality control.

Introduction: Substitution of estrogenes and progestins is the most common therapy and prophylaxis for postmenopausal discomforts like hot flushes, osteoporosis, etc. However in the majority of studies long term HRT has been associated with an slightly increased risk of breast cancer. On the other hand patients with preoperative HRT have a lower mortality and a longer overall-survival. Material and Methods: For further investigation we examined 544 patients between 45 and 60 years at time of first diagnosis of breast cancer with and without HRT with regard to the incidence of bone metastases. 154 patients were premenopausal (mean 48.0±2.7 y), 390 were postmenopausal (54.5±3.5 y), 208 of them received HRT (group HRT+) and 182 patients not (group HRT-). Patients of group HRT+ received estrogenes over a minimum of 12 months (mean 5.5 ±4.0y). Results: Although tumor size and grading of group HRT- were significantly higher than in group HRT+ (p = 0.024), nodal status, S-phase fraction, and hormone-receptor status showed no significant differences. Adjuvant treatment in the postmenopausal groups were also not significantly different. In regard to the incidence of metastases patients without HRT have significantly (p

This prospective study was performed to examine the safety and efficacy of a continuous infusion of ceftazidime in patients who developed febrile neutropenia after high-dose chemotherapy (HDCT) and autologous peripheral blood stem cell transplantation (PBSCT) and to determine if the underlying disease represents a risk factor for infectious complications. From September 1995 to May 2000, 55 patients with breast cancer (BC, group I, 54 females, one male) and 32 patients with multiple myeloma (MM, group II, 10 female, 22 male) were included in this study. The febrile patients received a 2 g intravenous bolus of ceftazidime, followed by a 4 g continuous infusion over 24 h using a portable infusion pump. If the fever persisted for 72 h a glycopeptide antibiotic was added. The median age was 42 years (range 22-59) in group I and 52 years (range 35-63) in group II. Thirty-five BC patients (64%) and 20 MM patients (63%) responded to the monotherapy with ceftazidime. After addition of a glycopeptide antibiotic, an additional 11 BC patients vs 10 MM patients became afebrile. The causes of fever in group I were fever of unknown origin (FUO) in 49 patients, microbiologically documented infection (MDI) in five patients, and clinically documented infection (CDI) in one patient. The causes of fever in group II were FUO in 22 patients, MDI in eight patients and CDI in two patients. Forty-one febrile episodes in BC patients (75%) and 22 episodes in the MM patients (69%) were successfully managed by out-patient treatment, resulting in a saving of an average of 20 days of inpatient care. Significantly more episodes of MDI and CDI occurred in patients with MM (P = 0.05). The results indicate that BC and MM patients with febrile neutropenia after HDCT and PBSCT can be treated as outpatients with close monitoring to ensure safety. This approach represents a better use of health care resources.

Objective: The monopolar, low-energy, high-frequency needle electrode is an innovative tool for electrosurgical dissection at laparoscopy. We reviewed the use of the needle and complications. Methods: A total of 1384 patients underwent laparoscopic operations including the new monopolar needle between 1990 and 1998. We reviewed indications for surgery, the intraoperative and postoperative course, indications for use of the needle, and complications. Results: The monopolar needle electrode was used for a wide range of indications, most commonly adhesiolysis (38.5%) and ovarian cystectomy (13%). Four patients developed superficial skin lesions, which were probably a result of patient positioning. Four patients with extensive adhesiolysis involving bowel developed bowel lesions. One patient developed postoperative bleeding after adnexectomy. Conclusion: The monopolar, low-energy, high-frequency needle electrode is a safe dissecting tool for laparoscopic surgery and has a wide range of indications.

In patients with metastatic breast cancer (MBC), early dose intensification with multiple cycles of peripheral blood stem cell-supported high-dose chemotherapy (HDCT) seems superior to a late dose-intensification strategy. We compared the progression-free survival (PFS) and overall survival (OS) of 20 patients treated with a double (D)-HDCT regimen to 20 patients who received a triple (T)-HDCT, matched by age, estrogen receptor (ER) status, adjuvant chemotherapy, initial disease-free interval, predominant metastatic site, and number of metastatic sites. At a median follow-up of 41.5 months (range, 14-88 months) an intent-to-treat analysis showed no difference in PFS (p = 0.72) and OS (p = 0.93) between the matched patients. For all 76 patients treated within the D- or T-HDCT trial, median PFS and OS was 13 months (range, 2-78 months) and 24.5 months (range, 7-78 months), respectively. In multivariate analysis independent predictors of shorter OS included negative ER (relative risk [RR] = 3.0 [95% confidence interval (CI) 1.5-5.9]; p = 0.002), more than two metastatic sites (RR = 2.4 [95% CI 1.0-5.7]; p = 0.049) and failure to achieve complete remission/no evidence of disease (CR/NED) after HDCT (RR = 4.5 [95% CI 2.0-10.1]; p < 0.0001). These data show that early dose intensification with T-HDCT is not superior to a D-HDCT regimen in patients with MBC. ER-negative tumors, more than two metastatic sites and no CR/NED after HDCT, are associated with inferior outcome.

OBJECTIVE A retrospective comparison of the efficacy and toxicity of docetaxel and paclitaxel in the treatment of metastatic breast cancer (MBC) was conducted based on our institution's experience since 1992. METHODS Two groups of 43 patients who received a similar chemotherapy regimen containing either docetaxel or paclitaxel were matched for the number of prior treatments. RESULTS Toxicity was mild in both groups. Tumour growth control, defined as either objective response or stable disease for at least 6 months, was obtained in a significantly higher proportion of patients treated with docetaxel compared with paclitaxel (67 % vs. 44 %, p = 0.001). Moreover, fewer patients progressed during treatment with docetaxel (28 % vs. 53 %, p < 0.001). At a median follow-up of 17 months there was no significant difference between the groups in median progression-free survival (7 vs. 5 months, p = 0.123) or median overall survival (OS) (12 vs. 11 months, p = 0.211). According to the method of Kaplan and Meier estimated OS rates at 1 year (74 % vs. 62 %) and 2 years (50 % vs. 26 %), however, were in favour of docetaxel. In a multivariate analysis only a positive hormone receptor status was significantly associated with improved OS. CONCLUSION These results suggest that docetaxel may be superior to paclitaxel in the treatment of MBC.

Objective : This study reviewed the results of breast reconstruction with the Fleur de lis-technique of the latissimus dorsi myocutaneous flap. Methods: We reviewed the cosmetic and functional results of 48 patients with breast cancer who underwent immediate or delayed breast reconstruction with the above technique. Results: A total of 44 patients (92%) considered the cosmetic results good or excellent. The surgeon considered the result good in 39 patients (81%). Complications consisted of seromas, wide scars, and dog ears at the donor site. Immediate reconstruction was not associated with increased morbidity. Conclusion: The Fleur de lis-technique of the latissimus dorsi myocutaneous flap is a safe technique with satisfactory cosmetic and functional results for immediate or delayed breast reconstruction.

PURPOSE: We evaluated the effect on future prognosis of an isolated locoregional recurrence (ILRR) after the primary diagnosis of breast cancer. Using data from four prospective studies of the German Breast Cancer Study Group, we investigated factors influencing prognosis after ILRR and defined a simple classification of patients into groups with different prognoses. PATIENTS AND METHODS: From 1983 to 1989, 2,746 patients were recruited into four studies comparing different treatments in primary breast cancer. After a median follow-up time of 8 years, 337 patients developed an ILRR as the first event. The influence of ILRRs on disease progression was examined. The effects of different prognostic factors on progression-free survival (PFS) and overall survival after ILRR were analyzed after a median follow-up time of 4.5 years. RESULTS: ILRRs increased the risk with respect to distant recurrence and death. After ILRR, 185 events occurred with respect to the PFS end point, and 171 patients died. Primary nodal status, tumor grade, estrogen receptor status of the primary tumor, and length of the disease-free interval (DFI) until the time of the ILRR had a significant prognostic impact. CONCLUSION: Determinants of prognosis after the ILRR should be taken into account for designing future risk-adapted clinical studies for these patients. Risk strata can be defined by a simple classification scheme based on primary nodal status and DFI.

Although metastasis is a frequent event in breast cancer patients, insight into the clinical course, prognosis and therapy with respect to the site of the first metastases has been poor and contradictory in former investigations. Follow-up data from 648 patients with metastatic breast cancer were statistically analyzed. Patients with bone metastases at first relapse had better overall survival (median 71 vs. 48 months; p < 0.001) and survival after first metastases (median 24 vs 12 months; p < 0.001) than patients with visceral metastases at first relapse. Bone was the site of first metastasis in 46%, and 71% of patients with metastatic breast cancer developed bone metastases. The localization of the second metastatic site was of prognostic relevance in patients with first visceral metastases, but not in patients with first bone metastases. The presence of osseous metastases correlated significantly with estrogen and progesterone receptor positivity, tumor grading I/II and S-phase fraction

Background: Epidemiological evidence which suggests that prolonged breastfeeding protects against breast cancer has accumulated in recent years. Issues with regard to the timing of breastfeeding and effect modification by correlates of breastfeeding and other risk factors of breast cancer remain unresolved. Methods: A population-based case–control family study of breast cancer among women diagnosed by the age of 50, conducted in two geographic areas in Germany, was used to evaluate the effect of breastfeeding on risk of breast cancer. Results: Among parous women in this study (553 cases, 1094 age-matched population controls), having ever breastfed a child for at least 1 month did not confer protection (odds ratio of 0.9 and 95% confidence interval (CI) 0.8–1.2). However, risk of breast cancer significantly decreased with increasing duration of breastfeeding (p for trend = 0.01) and the estimated relative risk was 0.6 (95% CI 0.4–0.9) for 13–24 months of cumulative breastfeeding and 0.5 (95% CI 0.3–1.1) for 25 months or more. Risk was less related to number of children breastfed than to increasing average length of breastfeeding per child (p for trend = 0.03). Conclusions: The reduction in risk associated with duration of breastfeeding was not primarily due to breastfeeding the firstborn and more evident in women who were older ( > 25 years) when they first breastfed and among women who experienced a recent full-term pregnancy. Risks were modified somewhat by a first-degree family history of breast cancer whereby a greater reduction in risk per additional month of breastfeeding was observed among women with a family history than those without (0.9 vs. 1.0). The study results support a protective role of prolonged breastfeeding against the development of breast cancer in predominantly premenopausal women in Germany.

We report on the efficacy and toxicity of a sequential high-dose therapy with peripheral blood stem cell (PBSC) support in 107 patients with high-risk stage II/III breast cancer. There were 90 patients with more than 9 tumour-positive axillary lymph nodes. An induction therapy of two cycles of ifosfamide (total dose, 7,500 mg/m(2)) and epirubicin (120 mg/m(2)) was given, and PBSC were harvested during granulocyte colony-stimulating factor (G-CSF)-supported leukocyte recovery following the second cycle. The PBSC-supported high-dose chemotherapy consisted of two cycles of ifosfamide (total dose 12,000 mg/m(2)), carboplatin (900 mg/m(2)) and epirubicin (180 mg/m(2)). Patients were autografted with a median number of 4.1 x 10(6) CD34+ cells/kg (range 1.9-26.5 x 10(6)), resulting in haematological reconstitution within approximately 2 weeks following high-dose therapy. The toxicity was moderate in general, and there was no treatment-related toxic death. Twenty-nine patients (27.1% of all patients) relapsed between 3 and 46 months following the last cycle of high-dose therapy (median 15 months). The probability of disease-free and overall survival at 3 years was 56% and 83%, respectively. A multivariate analysis showed that patients with stage II disease had a significantly better probability of disease-free survival (71%) in comparison with patients with stage III disease (30%). The probability of disease-free survival was also significantly better for patients with oestrogen receptor-positive tumours (62%) compared with patients with receptor-negative ones (40%). In conclusion, sequential high-dose chemotherapy with PBSC support can be safely administered to patients with high-risk stage II/III breast cancer. Further intensification of the therapy including the addition of non-cross-resistant drugs or immunological approaches may be envisaged for patients with stage III disease and hormone receptor-negative tumours.

We report on the efficacy and toxicity of a sequential high-dose therapy with peripheral blood stem cell (PBSC) support in 85 patients with high-risk stage II/III breast cancer. There were 71 patients with more than nine tumour-positive axillary lymph nodes. An induction therapy of two cycles of ifosfamide (total dose, 7.5 g m−2) and epirubicin (120 mg m−2) was given, and PBSC were harvested during G-CSF-supported leucocyte recovery following the second cycle. The PBSC-supported high-dose chemotherapy consisted of two cycles of ifosfamide (total dose, 12 000 mg m−2), carboplatin (900 mg m−2) and epirubicin (180 mg m−2). Patients were autografted with a median number of 3.7 × 106 CD34+ cells kg−1 (range, 1.9–26.5 × 106) resulting in haematological reconstitution within approximately 2 weeks following high-dose therapy. The toxicity was moderate in general, and there was no treatment-related toxic death. Twenty-one patients relapsed between 3 and 30 months following the last cycle of high-dose therapy (median, 11 months). The probability of disease-free and overall survival at 4 years were 60% and 83%, respectively. According to a multivariate analysis, patients with stage II disease had a significantly better probability of disease-free survival (74%) in comparison to patients with stage III disease (36%). The probability of disease-free survival was also significantly better for patients with oestrogen receptor-positive tumours (70%) compared to patients with receptor-negative ones (40%). Bone marrow samples collected from 52 patients after high-dose therapy were examined to evaluate the prognostic relevance of isolated tumour cells. The proportion of patients presenting with tumour cell-positive samples did not change in comparison to that observed before high-dose therapy (65% vs 71%), but a decrease in the incidence and concentration of tumour cells was observed over time after high-dose therapy. This finding was true for patients with relapse and for those in remission, which argues against a prognostic significance of isolated tumour cells in bone marrow. In conclusion, sequential high-dose chemotherapy with PBSC support can be safely administered to patients with high-risk stage II/III breast cancer. Further intensification of the therapy, including the addition of non-cross resistant drugs or immunological approaches such as the use of antibodies against HER-2/NEU, may be envisaged for patients with stage III disease and hormone receptor-negative tumours. © 1999 Cancer Research Campaign

Background The primary objective of treatment in women with severe hypertension and pre-eclampsia is to prevent complications such as encephalopathy and haemorrhage. In many countries dihydralazine is considered the drug of choice for treating hypertension in pregnancy, because it now has been used safely for about 30 years, and the introduction of a new drug in pregnancy is a difficult task with partially unknown hazards. In some other countries combined alpha- and beta-blockers are also used. Taking into account that some patients with pre-eclampsia do not respond to dihydralazine and the drug has serious side-effects like headache and reflex tachycardia, there is some need for developing alternative treatment strategies using drugs that are more adequate for pregnancy than dihydralazine. Methods Urapidil is a post-synaptic alpha 1 adrenoceptor antagonist, which is widely used to control hypertensive crises unrelated to pregnancy. Since it is known that pre-eclampsia is associated with increased sympathetic activity, administration of an alpha 1 adrenoceptor antagonist provides a reasonable therapeutic basis. So far there is only one report describing the i.v. use of urapidil in the treatment of hypertension in pregnancy unresponsive to dihydralazine and one report which describes the oral use of urapidil. In an earlier pilot study we examined the dose range for i.v. application of urapidil necessary for adequate blood pressure control in patients with pre-eclampsia. In the present randomized controlled study 26 white women with pre-eclampsia and hypertension in pregnancy were included. Treatment was not blinded. During the initial period of intensive intravenous treatment all subjects were under constant surveillance by a physician and a nurse. Results Effective prolonged control of blood pressure (values below 150/100 mmHg) was achieved in all patients of the two groups. In one patient of the dihydralazine group signs of lightheadedness and near syncope were noted. After this side-effect of dihydralazine the patient was treated with urapidil. At the end of the observation period the maternal heart rate in the dihydralazine group was higher than in the urapidil group. Conclusions Since urapidil decreased the high blood pressure in patients with pre-eclampsia without serious side-effects urapidil appears preferable superior to dihydralazine. The haemodynamic effects of urapidil were more predictable than those of dihydralazine. The reduction of intracerebral pressure could be an additional advantage of urapidil in the treatment of patients with pre-eclampsia.

Starting October 1991, 95 patients with a primary breast cancer were included in the present study performed at the Department of Obstetrics and Gynaecology of the Heidelberg University. In these 95 patients, remission after neoadjuvant chemotherapy (NACT), number of operations performed, rate of breast conserving procedures, and postoperative complications were evaluated by matched-pairs analysis. For the study group of 95 women, who underwent surgery from October 1991 to December 1994, in which we attempted to increase the breast conserving rate by NACT, a group of 95 patients without NACT (same histologic tumour stage, age, menopausal status) served as controls. Down staging was achieved in 80% of cases (n =78), a histologically complete remission in 2% (n=2). Tumour progression was seen in 9 patients (9%). Overall, 65% of the women (n = 62) in whom organ preservation would not have been possible without NACT, could be operated on by breast conserving surgery. The rate of secondary and tertiary modified radical mastectomies after NACT was 7.5 times, that of re-resections 6 times higher than in the control group (p

In patients with pelvic recurrences the therapeutic dilemma resides in the fact that despite radical tumor debulking tumor control can rarely be achieved. The impact of tumor debulking combined with IORT on local tumor control and overall survival was evaluated in patients with advanced disease. Patients and Methods: Between Januar 1992 and August 1995, 28 patients with pelvic recurrences were selected for tumor debulking plus IORT. Due to intraperitoneal metastases 9 patients had no IORT. Multi-organ resection was performed in 8 of 19 patients treated with tumor debulking plus IORT. In previously irradiated women (n =10) an IORT dose of 18 Gy, and in patients without prior irradiation 15 Gy plus 40 Gy external beam irradiation was given. Results: After a median follow-up of 26 months a significant difference (p = 0.032) was observed between those patients with (med. OAS 8 months) and without prior irradiation (med. OAS 16 months). Median OAS was 9 months in patients after complete resection (n=3), and 6.5 months after non-complete resection (p = 0.003). There were only two recurrences in the irradiation field. No perioperative complications were observed. One neuropathy (sensitive) occurred after 6 months. Conclusions: Using multi-modality approaches in pretreated patients with pelvic recurrences an good local tumor control could be achieved without increased mortality and morbidity. However, answers to a number of open questions are still lacking, such as the tolerance of healthy tissue to high doses of external irradiation with or without brachytherapy as boost technique, or questions related to the optimisation of individual selection criteria, resp. to the possible integration of IORT into the therapeutic concept of primary advanced gynecologic malignancies. Further optimisation of multi-modality treatment with maximal interdisciplinary effort will be essential.

The purpose of the present study was to analyse prognostic variables, predict the site of metastatic recurrence and to compare the clinical course and survival of patients with primary metastases. Material and methods: The records of 112 patients with primary metastatic breast cancer (disease-free interval less than 3 months or distant metastases at the time of diagnosis) treated at the Department of Gynaecology and Obstetrics of the University of Heidelberg between 1970 and 1990 were reviewed retrospectively. 648 patients with secondary distant metastases (disease-free interval of more than 3 months) served as controls. Results: The first metastatic site was the skeleton in 55 patients, visceral organs in 32 women, while 25 patients had concomitant osseous and visceral metastases. 58% of patients (n=32) with primary metastases confined to the skeleton had large tumours (T3-4) and 87% of these women were node-positive. Bone metastases were predominantly found in the axial skeleton (thoracic spine 69%, pelvis 55%, lumbar spine 51%). The symptoms and complications associated with bone metastases were: pain (67%), fractures (40%), hypercalcaemia (24%), myelopathy (13%) and spinal cord compression (7%). The median overall survival (OAS) in all 112 patients with primary metastatic breast cancer was 18 months. Kaplan-Meier analysis revealed that patients with bone metastases had a significantly longer overall survival (median 31 months) than those with visceral metastases (median 10 months). Conclusion: The existence of distant metastases at the time of diagnosis is usually associated with aggressive malignancy or an advanced primary tumour. 11.4% of patients with distant metastases were node-negative, which shows that the axillary lymph node status is not an ideal prognostic factor for assessing haematogenic metastases. Patients with primary metastatic breast cancer confined to the skeleton have a better prognosis than patients with visceral metastases. The metastatic affinity of highly differentiated tumours to the skeleton possibly contributes to the better prognosis of patients with skeletal metastases.

The ovarian carcinoma is characterised by an initial spread of the tumor via lymphatic fissures in the superficial peritoneal layers. The tumor is thus limited to the peritoneal cavity. Penetration and metastasising into the neighbouring organs will occur only subsequently. Intraperitoneal therapy using cytostatics and cytokines aims at complying with this pathomechanism. The ultimate target is high local efficacy with low systemic toxicity by intraperitoneal application of antineoplastic substances. This ideal goal, however, can be attained only if the mass of the tumor is small, since only a small tumor mass can guarantee satisfactory penetration and absorption via the peritoneum, taking the low depth of penetration into consideration. Hence, intraperitoneal therapy seems meaningful only in some specific indications. It appears, therefore, that the greatest benefit will be due to a salvage therapy in case of small residual tumors after primary therapy, such tumors being identified only microscopically, or if the individual lesion has a maximum diameter of less than 0.5 cm. Another indication, albeit without any dimensional tumor parameter, is a consolidating therapy in patients with advanced ovarian carcinoma and complete, surgically obtained remission. Besides the surgical technique of inserting a part system with emphasis on endoscopy, we can now report on our experience with various cytostatics and cytokines on intraperitoneal administration. Generally, substances like cisplatin, carboplatin, as well as mitoxantron and paclitaxel, are used. New substances such as topotecan have also been found interesting and hopeful. Our own results were good when using recombinant tumor necrosis factor alpha with interferon alpha or gamma, depending on the residual tumor mass, against minimal residual tumor parts (< 0.2 cm), and depending on the dosage. Intraperitoneal therapy can only be applied if there is sufficient intraperitoneal space without adhesion, as well as the use of volumes that are sufficiently large for good distribution. To confirm the indications for intraperitoneal treatment as stated above, it would be desirable to conduct further clinical randomised studies. The pathoanatomical and pharmacokinetic prerequisites mentioned above must be taken into consideration if intraperitoneal treatment is envisaged. Over and above this, the physician concerned should command over experience in the systemic application of cytostatics and cytokines.

Patients with an elevated level of urokinase plasminogen activator (uPA) in breast cancer tissue have an adverse prognosis. This study evaluated the prognostic relevance of uPA detection in disseminated tumour cells in bone marrow. Bone marrow was sampled intraoperatively from both iliac crests in 280 patients with primary breast cancer. Interphase cells were enhanced and stained immunocytologically with two antibodies: 2E11, which detects TAG 12--a tumour-associated glycoprotein typically expressed by almost all breast cancer cells--and the anti-uPA antibody HD-UK9. Thirty-five of the 2E11-positive women (n = 132, 47%) developed metastatic disease (median follow-up time 44 months). Of these, most were uPA positive (n = 23, 65%) and only 12 were uPA negative. Patients with uPA-positive cells in bone marrow (n = 98, 35%) had a significantly shorter metastasis-free interval (36 months) than women who were uPA negative (44.5 months). The worst prognosis was seen in patients positive for both markers (29.5 months), followed by those who were uPA negative and 2E11 positive (37 months). The detection of uPA on disseminated tumour cells characterizes a subgroup of patients with an even worse prognosis, who should undergo more aggressive adjuvant systemic therapy. For the first time, it was possible to evaluate an important qualitative parameter involved in the process of breast cancer metastases. Images Figure 1

From 1970 to 1994 the age-standardised mortality rates increased by 16% in breast cancer and by 9% in ovarian cancer in the (old) Federal Republik of Germany. Contrasting with these data, endometrial cancer decreased by 42% and cervical cancer by 46%. The mortality rates of these four tumours togehter have remained constant since 1970 and amount to 73 deaths per 100000 women. Within these four tumour entities a shift towards higher age groups can be observed. In ovarian cancer the incidence rate is 20% higher than the mortality rate, while the incidence rates in the other three tumour types exceed the corresponding mortality rates 2.5- to 3.5-fold. The median age of death is between 65 years (cervical cancer) and 75 years (endometrial cancer). Since 1988 no further increase of the mortality rates of breast and ovarian cancer can be observed. A more reliable estimate of mortality and incidence rates would require continuous cancer registries of high quality.

Consensus about risk-adapted systemic therapy of node negative breast cancer patients remains difficult because of the lack of reliable prognostic factors. Approximately 30% of nodal-negative breast cancer patients will relapse within 10 years and 10-20% of those with distant metastases will be lymph node-negative at the time of surgery. Evaluation of potentially new prognostic factors, therefore, have to concentrate on this issue. Tumor cell detection (TCD) in bone marrow indicates the presence of tumor cell shedding in malignant disease. In a prospective study we examined TCD immunocytologically in 1026 women who underwent primary breast cancer surgery at the Women's Hospital of the University of Heidelberg (1985-1995). Bone marrow aspiration at two sites on each anterior iliac crest was performed immediately after surgery under general anesthesia. Most patients received some type of systemic adjuvant treatment. The monoclonal antibody 2 E11, directed against the breast-mucin TAG 12, was used to detect tumor cells in bone marrow samples. The statistical analysis of follow-up data included Kaplan-Meier estimation of survival curves, logrank tests and multivariate Cox regression analysis with stratification by adjuvant therapy. TCD was positive in 53% of 480 node positive and in 31% of 546 node-negative patients. TCD correlated significantly with larger tumors (p

Morphometric Microvessel quantitation as New Prognostic Factor: Tumour growth and early development of metastases depend on the capacity of the tumour to induce neovascularisation, and hence on angioneogenesis. To evaluate the prognostic relevance of microvessel density, established prognostic parameters as well as vascular density were determined in the tumour tissue of 67 patients with breast cancer. Vascularisation of the tumour was identified immunohistochemically with a monoclonal antibody against the vascular endothelium-associated antigen CD31.A morphometric, stereological procedure was used for microvascular quantitation, establishing microvascular volume, surface and length. The vascular density thus calculated was correlated with conventional prognostic factors such as tumour size, nodal status, receptors, s-phase fraction. A statistically significant correlation was found between vessel length and oestrogen as well as progesterone receptors (p=0.007, p=0.005). Thus receptor negative tumours were shown to be characterised by increased vessel length and hence higher vascularisation. At a median follow-up of 38 months, in the group of n = 48 patients, which could be followed-up, with a microvessel length of ≥ 190 mm/mm 3 , had a statistically significant shorter overall survival (p = 0.014), and also a statistically relevant higher rate of metastasising and recurrence (p

PURPOSE We investigated quality and efficacy criteria of an autologous, physically and immunologically purified, Newcastle disease virus (NDV)-modified, irradiated tumor-cell vaccine (ATV-NDV) by analyzing three independent cohorts (a through c) of patients vaccinated between 1991 and 1995. MATERIALS AND METHODS Included were 63 patients with primary breast cancer (a), 27 with metastatic pretreated breast cancer (b), and 31 with metastatic pretreated ovarian cancer (c). In addition to vaccine, cohorts b and c received nonspecific immunotherapy as supportive treatment. After cryoconservation and purification, the vaccines varied in applied numbers of viable cells and dead cell contaminations. We retrospectively hypothesized that an immunogenic vaccine should contain at least 1.5 x 10(6) viable tumor cells and viability should be at least 33%. Each cohort was thus divided into two groups; one that received vaccine type A (A), fulfilling both criteria; and the other type B (B), missing one or both criteria. RESULTS Conventional prognostic factors were wall balanced between A and B in cohorts a and c. In cohort a, there was a benefit in survival (P = .026) and disease-free survival (P = .089) for A. In addition, in cohort a, the relative risk of dying in the group that received A as compared with B was 0.2 (univariate Cox model). There were also survival trends in favor of A versus B (P = .18 and P = .09, respectively) in cohorts b and c, with relative risks of 0.5 and 0.42, respectively. In cohort b, the survival benefit could not be ascribed to vaccine quality alone, because of prognostic imbalance in favor of A. CONCLUSION In cohort c, like in cohort a, the survival benefit for A may be ascribed to the ATV-NDV vaccine quality, since prognostic factors were not biased. This could imply clinical effectivity in breast and ovarian cancer with ATV-NDV high-quality vaccine. Furthermore, the data provide clinically relevant information for standardization and quality control of autologous tumor-cell vaccines. A randomized study is urgently needed.

Objective : The aim of the present investigation was to study the association betweenendogenic and exogenic risk factors towards the female pelvic floor and the prevalence of urinary stress incontinence. Study Design : In a case-control study a sample of 928 women aged 20-86 years were analysed by a questionnaire. The study group consisted of former patients, who underwent descensus or incontinence surgery at the Womens' University Hospital in Heidelberg between 1980-1992, as well as of a random selected population of working women. A total of 653 (70%) were affected by urinary incontinence, the other 275 (30%) in the control group were continent. Results: After evaluation of the data by statistical means those were selected from a variety of risk-factors, which were statistically significant associated with urinary stress incontinence. By means of logistic regression analysis these factors were brought together in a chart according to their potency of relative risk: risk factor: 1. body weight, 2. parity, 3. carrying weights at work, 4. postmenopause, 5. assembly-line work, 6. internal work, 7. heavy housework, 8. cold temperatures during work. Conclusion: In this investigation it could be proved for the first time not only the significance of endogenous and exogenous risk factors with respect to the correlation to female urinary incontinence, but also to analyse their predictive value.

Despite the use of different adjuvant therapies locoregional relapse and skin metastases remain a therapeutic and psychological problem in the treatment of patients with breast cancer. In the present study the efficacy of a topical treatment of Miltefosine (hexadecyl-phosphocholin), 6% solution, was examined in heavily pretreated patients with skin metastases or locally recurrent breast cancer. One hundred and forty-two patients were treated with Miltefosine under conditions of a phase II multicenter study. Response could be evaluated in 109 patients. The response rate that could be achieved was 26% (complete and partial remission). A no change situation was found in 50% and in 24% tumor progression took place. The longest median time to progression with 31 weeks was achieved by patients with concomitant endocrine therapy, while in patients with accompanying chemotherapy or without any further therapy time to progression was 16 weeks. The treatment was well tolerated by the majority of patients. No systemic side effects were found. In 65/140 patients local adverse reactions were observed, presenting as pruritus in 24%, rash (erythema) in 15%, exfoliation in 16% and the feeling of dry skin in 10%. Miltefosine solution is an effective and safe new treatment modality for skin lesions in patients with breast cancer. Best results can be achieved in flat nodular lesions with an infiltration up to 1 cm. Due to simple handling, the patients themselves can apply the topical treatment and are thus actively integrated in the therapeutic concept.

Photodynamic laser therapy was developed as a new approach in the treatment of superficial tumours. For treatment we use a photosensitising drug which is applied intravenously. This is activated by light of a certain wavelength. Contrary to conventional laser therapy the antitumorous effect is not caused by thermal but by photo-chemotoxic activity. In the Women's University Hospital in Heidelberg the photodynamic therapy is a palliative method in the treatment of recurrent skin metastases of breast cancer after conventional methods failure of conventional methods (excision, thermical laser destruction, radiation, chemotherapy). After histological examination of biopsies of the treated skin tissue we found a very high response rate of the tumour cells after laser treatment with tumour cell destructin from 70-100%. Tissue biopsies in the long term follow-up are still missing. Different indications (i.e. extramammarian M. Paget) are explored and planned for controlled clinical trials.

For answering the question at which hysteroscopical procedures an intraoperative screening method is necessary to avoid a fluid overload and whether a beginning fluid absorption can be diagnosed early by adding ethanol to the distension medium, a prospectively randomised comparative study of ablative versus non-ablative operative hysteroscopy with differing ethanol concentrations was performed (n = 120). Purisole (a mannit/sorbit solution) was used a distension medium. The measuring parameters (breath alcohol, amount of absorbed fluid, haematocrit and haemoglobin values, central venous pressure, heart frequency) were intraoperatively determined at 5-minute intervals. The results of the study show that with those hysteroscopical procedures during which the endometrium is not or only minimally injured (e.g. syneciolysis, hysteroscopic proximal tubal catheterisation). Intraoperative screening is not necessary due to the low absorbing amounts. With hysteroscopical procedures such as resection of myoma, endometrium ablation and septum resection, however, an addition of ethanol of 2% to the distension medium has proved useful, because with this method absorption amounts of 400 ml and more can be detected by positive values of breath alcohol. As the result of a further absorption of fluid, delayed in time compared to the first positive value of breath alcohol, there is an increase in central venous pressure and hyponatraemia. Intraoperative ethanol monitoring is a non-invasive procedure which can be performed during ablative-operative hysteroscopies and has no negative influence on the course of the intervention and the general condition of the patients.

Because of the high tendency of breast cancer to develop metastatic deposits in the skeleton, space-occupying processes in the sternal region are mostly attributed to osseous metastases and not to parasternal lymph node involvement, even in case of solitary lesions, primary tumor localizations in the inner quadrants, positive axillary nodes and negative X-ray or bone scan findings. The sonographic examinations of 115 patients with breast cancer and clinical and/or scintigraphic suspicion of sternal metastasis, however, revealed the typical bone metastases of the sternum with a small soft tissue tumors in only 27.8 %, whereas 59.1 % of the cases showed parasternal recurrences; 5.2 % had both. Non-tumorous changes were seen in 6.1 %, equivocal results in 1.7 %. Solitary osseous metastasis of the sternum was rare; multiple skeletal lesions were found in the majority of this group in contrast to the patients in the parasternal relapse group, which moreover showed strong overrepresentation of the primary tumor localization in the inner quadrants. X-rays of the chest or the sternum were often false-negative and not reliable, the bone scans positive only in cases of secondary sternal invasion or skeletal metastases. Concerning reliability and cost, sonography was the imaging method of first choice for diagnosis, therapy planning and follow-up for space-occupying processes in the sternal region, with CT or MRI as adjuncts in cases of extended tumors invading the mediastinum.

The plasminogen activator system plays a key role in the proteolysis of malignant tumours. In 155 patients with primary breast cancer levels from PAI-1 and uPA were measured in cytosol with monoclonal antibodies and by an enzyme-linked immunosorbent assay. 35 tumour tissue samples form benign breast were also examined. Malignant tumours contain higher levels of PAI-1 (8.6 ng/mg) than benign tumours (1.28 ng/mg) (p 5%). After a median follow-up of 46 months we found that high levels of PAI-1 correlated with short DFS (p = 0.0005) and OAS (p = 0.003). However, in the Cox multivariate regression analysis only PAI-1 was significantly independent for OAS and could therefore give additional information. We conclude that levels from PAI-1 antigen measured in cytosol of primary breast cancer is an independent prognostic parameter to identify patients with high and low risk for relapse and for individualised treatment.

Fragestellung: An einem Kollektiv von 300 Patientinnen der Universitats-Frauenklinik Heidelberg wurde ein Managementschema zur uteruserhaltenden Myomtherapie unter Einbeziehung endoskopischer Techniken erarbeitet. Methode: Trotz des Wunsches nach Uteruserhalt musste bei 12 Patientinnen (abgeschlossene Familienplanung, therapieresistente Sterilitat, fehlender Kinderwunsch) bei exzessiver Uterusgrosse (20.-24. SSW) bzw. degeneriertem intramuralem Myom bei nicht ausgeschlossenem Sarkom eine primare Hysterektomie durchgefuhrt werden. Insgesamt wurden 37,9% der Patientinnen konventionell, 42% per Laparoskopie und 20,1% per Hysteroskopie operiert. Zur Objektivierung der Rolle einer Vorbehandlung mit GnRH-Analoga (GnRHa; n = 128 Patientinnen mit vs. 160 ohne GnRHa) wurden zusatzlich als Prufparameter primare Laparotomierate, Umschalterate, sekundare Hysterektomierate, intraoperative Blutungen, Menge des Distensionsmediums sowie die Anzahl der Wiederholungseingriffe untersucht. Ergebnisse: Bezuglich der Wertigkeit der GnRHa-Therapie fanden sich in der Laparoskopiegruppe keine signifikanten Unterschiede zwischen Studien- und Kontrollkollektiv. In der hysteroskopischen Gruppe waren die Unterschiede bezuglich Umschalterate (13,3 vs. 7%), Operationszeit (35 vs. 21,9 min), verstarkter intraoperativer Blutungen (33,3 vs. 9,3%), Menge des verbrauchten Distensionsmediums (Unterschied 2,1 Liter) und Wiederholungseingriffen (40,0 vs. 16,3%) zwischen Studien- und Kontrollgruppe signifikant. Ebenfalls war die Rate der primaren Laparotomien in der GnRHa-Gruppe signifikant niedriger (31,2 vs. 43,1%). Schlussfolgerung: Hinsichtlich des therapeutischen Managements steht die Frage im Vordergrund, wann uberhaupt invasiv vorgegangen werden sollte. Die zweite Frage muss sein, welcher Zugangsweg sinnvoll ist. Die Entscheidung zur praoperativen GnRHa-Therapie muss ebenfalls individuell erfolgen, gerade bei konventionellen bzw. laparoskopischen Myomenukleationen. Obligatorisch ist die praoperative GnRHa-Therapie vor hysteroskopischen Operationen submukoser Myome.

We present the case of a 56-year-old woman, who was admitted to our clinic for diagnostic laparoscopy because of a cystic uterine tumour of uncertain dignity. In the patient's history three curettages due to recurrent acyclic premenopausal vaginal bleeding were reported without specific histological findings. The preceding MRI described the structure as a myoma. During preoperative diagnostics an arteriovenous malformation was suspected by transvaginal Doppler sonography. Consequently the procedure was changed and a laparotomy performed. The sonographic findings were confirmed during surgery and by histological examination. This case points out the important role of transvaginal sonography combined with colour-flow-mapping. By confirming the diagnosis preoperatively and changing the management a low-risk procedure could be ensured.

Within the framework of "minimal access surgery" a prospective randomised study was initiated at the Dept. of Obstetrics and Gynaecology of Heidelberg University to examine the feasibility of endoscopical abdominal Burch colposuspension for stress incontinence (II-III), at laparoscopy and "retziusscopy". Further, also prospectively randomised, two suspension techniques: needle suspension and suspension by means of alloplastic material with stapler fixation, were compared, irrespective of the endoscopic approach chosen, especially because long-term results of our study population on colposuspension with fibrin glue which are now available, are below expectations, worse than those obtained with conventional techniques. Except for a bladder lesion (during laparoscopic dissection of the space of Retzius) no intra- or postoperative complications occurred in the pilot study group of 20 patients. Both types of endoscopic access proved technically feasible, and presented the typical advantages of minimal access surgery such as short hospitalization and rapid recovery. Short-term follow-up (2-12 months) showed subjective and objective results (continence in 18/20 patients), comparable to conventional abdominal procedures at laparotomy. Detailed evaluation of subgroups is not yet possible, since the number of patients it still too small and follow-up too short.

In a total of 77 patients with epithelial ovarian carcinomas, new biologic parameters [estrogen and progesterone receptor (ER, PR), DNA-ploidy (DP), S-phase fraction (Spf), cycling index (Ki67), Her2b/neu oncoprotein, epidermal growth factor receptor (EGF-R), cathepsin D and P170 glycoprotein] have been simultaneously detected and correlated to the clinical outcome [progression-free (PFI) and overall survival (OAS)] in a preliminary study. Apart from conventional prognosticators (age, stage, grade, residual tumor) and the postoperative serum marker Ca125, DP (P = 0.01), Spf (P = 0.009), Ki67 (P = 0.05) and PR (P = 0.01) could predict a short OAS (log rank test), whereas cathepsin D was of borderline significance only. Prognostic significance could be improved by using combinations of different factors [two markers of differentiation (DP, PR), one marker of proliferation (Spf) and one marker describing local tumor spread (cathepsin D)]. The difference in prognosis between patients with either all or three favorable tumor factors and patients with two to four unfavorable tumor factors reached a similar significance as can be obtained using FIGO stage as a prognostic factor (P = 0.007 for PFI, P = 0.0005 for OAS). These results were similar if early stages (FIGO I and II) were excluded. However, in a Cox regression analysis, including stage and residual tumor, this combination was significantly independent for PFI and OAS and could give additional information. Therefore, the large number of new biologic tumor markers could be restricted to only a few significant prognosticators to predict prognosis in primary epithelial ovarian carcinoma. In the future tumor characterizations may allow more individualized treatment with more aggressive, or even without, cytotoxic therapy after primary surgery.

Primary (neoadjuvant) chemotherapy of locally advanced breast carcinomas is performed to locally reduce the tumour mass and to improve the operability. Recently, the indication for primary chemotherapy has been extended for preoperative treatment in breast conserving surgery. In an ongoing clinical trial we examined the resection specimens of 51 mammary carcinomas after primary chemotherapy. These patients had received a neoadjuvant therapy with epirubicin/cyclophosphamide for size reduction of large (> 3 cm) but operable tumours (pretreatment median tumour size 4.5 cm by mammography). The tumour response was evaluated pathologically and compared with the clinical tumour regression that was observed in over two-thirds of all cases. We classified the regressive changes using a semiquantitative scoring system from 0 to 4 (0 = no effect, 1 = resorption and tumour sclerosis, 2 = minimal residual invasive tumour [< 0.5 cm], 3 = residual noninvasive tumour only, 4 = no tumour detectable). The aim of this study was to evaluate the improvement of operability objectively and to correlate the histology of the primary tumour with the response to treatment. With invasive lobular carcinomas, the tumour size after therapy was reduced less than average and irrespective of the amount of histological tumour cell reduction, largely due to the stromal content of these neoplasms. Invasive ductal carcinomas with extensive or predominant intraductal component also underwent only a slight decrease in tumour size; this was because of the lack of tumour response with the intraductal component. Well differentiated tubular carcinomas were particularly resistant to primary chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PURPOSE In 1984, the German Breast Cancer Study Group (GBSG) started a multicenter randomized clinical trial to compare the effectiveness of three versus six cycles of 500 mg/m2 cyclophosphamide, 40 mg/m2 methotrexate, and 600 mg/m2 fluorouracil (CMF) on day 1 and 8 starting perioperatively with or without tamoxifen (TAM) (3 x 10 mg/d for 2 years). The aim of the trial was to compare recurrence-free and overall survival between the different treatment modalities. PATIENTS AND METHODS During 5 years, 41 institutions randomized 473 patients (3 x CMF: 145; 3 x CMF + TAM: 93; 6 x CMF 144; 6 x CMF + TAM: 91). Until March 31, 1992, median follow-up time was 56 months with 197 events for disease-free survival and 116 deaths observed. This provides a power of approximately 80% to detect a potential treatment difference corresponding to a relative risk (RR) of 0.67 for recurrence-free survival. Treatment modalities and various patient characteristics were evaluated by means of a multivariate Cox regression analysis. RESULTS No significant difference in recurrence-free survival was observed with respect to hormonal therapy (RR = 0.75 TAM v no TAM; 95% confidence interval [CI], 0.54 to 1.04; P = .08) as well as duration of chemotherapy (RR = 0.90 of 6 x CMF v 3 x CMF; 95% CI, 0.67 to 1.19; P = .45). Similar results were obtained for overall survival. The multivariate analysis revealed a significant prognostic impact of the number of positive lymph nodes and the progesterone receptor level on recurrence-free survival. Compliance with chemotherapy within the range of 85% to 115% of the target dose was achieved in 94% and 78% of the patients randomized to 3 x CMF and 6 x CMF, respectively. Sufficient compliance with TAM was reported for 141 patients (93%). CONCLUSION At this stage of follow-up, six courses of CMF are not superior to three courses with respect to recurrence-free survival.

Hysteroscopic endometrial ablation under maximal anaesthesiological surveillance was performed in 34 high-risk patients to avoid hysterectomy. It was a collective of patients with heavy thrombo-embolic or thrombotic disease, either under permanent anticoagulation due to residual disease or multiple endoprosthetic treatment, or with endogenous coagulopathy. In all these women, hysterectomy was either a relative or an absolute contraindication. In 22 patients, treatment resulted in complete amenorrhoea or at least hypomenorrhoea (without menometrorrhagia) respectively cyclic spotting. In 6 further patients, amenorrhoea was achieved after a repeat procedure. Endometrial ablation was thus successful in 28 of 34 cases. In these patients, hysterectomy with the risk of major or even lethal complications, could thus be avoided. Hysterectomy, however, had to be performed in 2 women with extensive adenomyosis uteri interna. Within two respectively three years after endometrial ablation, two other patients died from causes unrelated to the surgical intervention (cardiac infarction, cerebral haemorrhage). Follow-up ranged from 1 to 5 years. Hysteroscopic endometrial ablation proved an effective therapeutic option in this selected group of patients. Other indications require further study.