Lokalrezidive verschlechtern die Prognose und sollten durch eine optimale Primärtherapie möglichst verhindert werden. Beim isolierten Lokalrezidiv (ohne Fernmetastasen) ist eine konsequente lokale Therapie mit kurativer Intention (Operation, Strahlentherapie, Hormontherapie) indiziert. Die Fünfjahresüberlebensraten nach Therapie eines Lokalrezidivs betragen, je nach Konstellation, etwa 30%. Ein kurativer Effekt einer Chemotherapie ist nicht belegt.

The analysis of tissue specific gene expression by reverse transcription based RT/PCR methods is currently evaluated as a method for the detection of tumor cell dissemination in patients with cancer. Breast cancer tissues express PTHrP and the level of PTHrP expression in the primary tumor correlates with the incidence of metastases in the bone. We applied a RT/PCR assay of PTHrP to detect tumor cells in the mononuclear cell fraction of peripheral blood (pb) and bone marrow (bm) of patients with newly diagnosed breast cancer. PTHrP positivity was found in 18/67 pb and 20/71 bm samples. In a median follow up of 23 months there were 7 metastatic relapses (4 osseous, 2 hepatic, 1 pulmonary) and 9 local relapses in patients with primary lymph node positive breast cancer. The hepatic and pulmonary relapses had been both PTHrP-PCR negative in pb and in bm. Of the 4 patients with metastatic relapses to the bone the samples of bm had been initially negative in all cases, the pb had been positive in 2 cases. Of the 9 patients with local recurrences the pb alone had been positive in 4 patients, 5 patients had been negative in both the pb and the bm. During the period of observation there was no local and metastatic relapse detectable in the group of patients with primary lymph node negative breast cancer. In summary the increased risk for local or systemic relapse would have been predictable by RT/PCR of PTHrP alone in pb in 4 of the 9 local and in 2 of the 7 early metastatic relapses. Further follow-up of the patient cohort analysed is needed to assess the value of the RT/PCR of PTHrP as a prognostic and predictive marker in patients with breast cancer.

In this report, the results of the first controlled clinical trial on breast cancer in Germany, begun in 1983, are presented after a median follow-up of 8 years. Four-year results have been previously published. In pT1 N0 M0 breast cancer, mastectomy as the standard treatment was to be compared with tumorectomy plus radiotherapy to the remaining breast tissue. The study design, originally planned as a comprehensive cohort study including randomised and non-randomised patients, had to be changed into a prospective observation study due to the low randomisation rate. 1036 out of 1119 recruited patients were evaluable. After a median follow-up of 97 months, 237 events (local recurrence, regional recurrence, distant metastases, contralateral breast cancer or death of the patient without previous recurrence) occurred. With the exception of death without recurrence, the events were evenly distributed among the two treatment groups. The 8-year local recurrence rate of the whole patient population is 8.8%. Out of all prognostic factors examined, only tumour size and grade had a significant influence on recurrent disease. Event-free survival decreased in cases with 'uncertain' tumour margins, whereas the width of the margin has no influence on disease recurrence. Based on 151 deaths observed so far, there was no significant difference in overall survival between the two treatment groups. The 8-year results of this study are in accordance with the 4-year results reported previously and with those of other breast-conserving treatment trials. There was no significant difference between the two treatment groups with regard to event-free and overall survival. Incomplete tumorectomy had a negative influence on recurrence.

Der Nachweis disseminierter Tumorzellen im Knochenmark gilt als ein unabhängiger Prognosefaktor bei Patientinnen mit einem primären Mammakarzinom. Dabei korreliert die Knochenmarkinfiltration mit dem Auftreten eines frühzeitigen Rezidivs und einer verkürzten Gesamtüberlebenszeit [1]. In den bisherigen Studien erfolgte der Nachweis einer Tumorinfiltration immunzytologisch und/oder immunhistochemisch unter Gebrauch monoklonaler Antikörper, die entweder gegen tumorassoziierte Antigene oder gegen Antigene der Epithel- oder Mamma-typischen Differenzierung gerichtet waren [2]. Eine Methode zum Nachweis kleinster Tumorzellreste ist die Reverse-Transkription/Polymerase-Kettenreaktion (RT/PCR) zum Nachweis gewebespezifischer mRNA-Expression [3]. Auf der Suche nach neuen PCR-Methoden zum Nachweis minimaler Tumorzelldissemination wurde das Parathyroid Hormone-related Protein (PTHrP) untersucht. PTHrP ist ein funktionelles Analogon zum Parathormon und wurde ursprünglich als einer jener Faktoren entdeckt, die das Hyperkalzämie-Syndrom bei Malignomerkrankungen verursachen [4]. In der Brustdrüse konnte PTHrP sowohl in ruhenden (GO) und Milch-produzierenden, nicht-transformierten Zellen als auch in 63% primärer Mammakarzinome nachgewiesen werden [5, 6]. Zudem wurde PTHrP in 92% von ossär metastasierten Mammakarzinomen detektiert, wobei der Grad der PTHrP-Expression mit der Inzidenz ossärer Metastasen korrelierte [7, 8]. Im Rahmen einer prospektiven Studie untersuchten wir die RT/PCR von PTHrP-Transkripten zur Detektion von disseminierten Tumorzellen im Knochenmark (KM) und peripheren Blut (PB) von Patientinnen mit primärem Mammakarzinom. Zudem sollte durch Verlaufsbeobachtung geklärt werden, inwiefern der Nachweis von PTHrP-Transkripten einen prädiktiven Wert bezüglich des Auftretens von Lokalrezidiven und Fernmetastasen darstellt.

In this report, the results of the first controlled clinical trial on breast cancer in Germany, begun in 1983, are presented after a median follow-up of 8 years. Four-year results have been previously published. In pT1 N0 M0 breast cancer, mastectomy as the standard treatment was to be compared with tumorectomy plus radiotherapy to the remaining breast tissue. The study design, originally planned as a comprehensive cohort study including randomised and non-randomised patients, had to be changed into a prospective observation study due to the low randomisation rate. 1036 out of 1119 recruited patients were evaluable. After a median follow-up of 97 months, 237 events (local recurrence, regional recurrence, distant metastases, contralateral breast cancer or death of the patient without previous recurrence) occurred. With the exception of death without recurrence, the events were evenly distributed among the two treatment groups. The 8-year local recurrence rate of the whole patient population is 8.8%. Out of all prognostic factors examined, only tumour size and grade had a significant influence on recurrent disease. Event-free survival decreased in cases with ‘uncertain’ tumour margins, whereas the width of the margin has no influence on disease recurrence. Based on 151 deaths observed so far, there was no significant difference in overall survival between the two treatment groups. The 8-year results of this study are in accordance with the 4-year results reported previously and with those of other breast-conserving treatment trials. There was no significant difference between the two treatment groups with regard to event-free and overall survival. Incomplete tumorectomy had a negative influence on recurrence.

In the prospective nonrandomized observation study "Therapy of Small Breast Cancer", which was the first multicenter trial on breast cancer ever conducted in Germany, mastectomy (303 cases) was compared with breast-preservation therapy (733 cases) in patients with stage pT1NOMO breast cancer. After a median follow-up of 8 years, there is no difference between the treatment modalities with regard to disease-free and overall survival which compares well with the results Of international randomized studies. There is no difference in treatment outcome between centers specialized in the therapy of breast diseases in comparison to less experienced institutions as long as a high standard of treatment performance is guaranteed by reference centers.

Since 10/1994 the Interdisziplinäre Kurzzeit-Onkologie (IKO) is an outpatient department for the treatment of patients with cancer used by the departments of hematology/oncology and surgery. Between 09/1995 and 02/1997, 818 patients received 2024 cytotoxic therapies with neoadjuvant (15%), adjuvant (65%) or palliative (20%) intention-mostly within multicenter clinical studies. Ambulatory operations like removal of lymph nodes for diagnosis or the implantation of venous catheter systems prepared the way for specialized modalities of cancer therapy. The high compliance and consent of patients, combined with better understanding of cancer therapy, resulted in an enhanced quality of life and optimized therapy. Standardization in diagnostics and fast realisation of interdisciplinary treatment schedules lead to reduction of costs and to enhancement of quality and security in cancer therapy.

In the prospective nonrandomized observation study "Therapy of Small Breast Cancer", which was the first multicenter trial on breast cancer ever conducted in Germany, mastectomy (303 cases) was compared with breast-preservation therapy (733 cases) in patients with stage pT1N0M0 breast cancer. After a median follow-up of 8 years, there is no difference between the treatment modalities with regard to disease-free and overall survival which compares well with the results of international randomized studies. There is no difference in treatment outcome between centers specialized in the therapy of breast diseases in comparison to less experienced institutions as long as a high standard of treatment performance is guaranteed by reference centers.

Die Interdisziplinäre Kurzzeit-Onkologie (IKO) ist eine Einrichtung zur ambulanten Behandlung von Tumorpatienten, die seit 10/1994 gemeinsam von den Abteilungen Hämatologie/Onkologie und Allgemeinchirurgie genutzt wird. Im Zeitraum 09/1995 bis 02/1997 erfolgten durch die Allgemeinchirurgie bei 818 Patienten 2024 zytostatische Infusionstherapien neoadjuvant (15%), adjuvant (65%) oder palliativ (20%) — zumeist im Rahmen von multizentrischen Therapieoptimierungsstudien. Ambulante Operationen — wie diagnostische Lymphknotenexstirpationen und die Implantation venöser Portsysteme — erbrachten zudem Voraussetzungen für spezielle Therapiemodalitäten. Die hohe Compliance und Akzeptanz der Patienten sowie die verbesserte Transparenz der Tumorbehandlung stellen einen Zuwachs an Lebensqualität und somit eine Behandlungsoptimierung dar. Die Standardisierung der Tumordiagnostik und die zügige Umsetzung interdisziplinärer Therapiekonzepte leisten neben einer Kostenreduktion einen positiven Beitrag zur Qualitätssteigerung und -sicherung in der onkologischen Therapie.

Since 10/1994 the Interdisziplinare Kurzzeit-Onkologie (IKO) is an outpatient department for the treatment of patients with cancer used by the departments of hematology/oncology and surgery. Between 09/1995 and 02/1997, 818 patients received 2024 cytotoxic therapies with neoadjuvant (15%), adjuvant (65%) or palliative (20%) intention mostly within multicenter clinical studies. Ambulatory operations like removal of lymph nodes for diagnosis or the implantation of venous catheter systems prepared the way for specialized modalities of cancer therapy. The high compliance and consent of patients, combined with better understanding of cancer therapy, resulted in an enhanced quality of life and optimized therapy. Standardization in diagnostics and fast realisation of interdisciplinary treatment schedules lead to reduction of costs and to enhancement of quality and security in cancer therapy.

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.

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/m(2) cyclophosphamide, 40 mg/m(2) methotrexate, and 600 mg/m(2) flourouracil (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 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.

Within six years between November 1983 and December 1989 the German Breast Cancer Study Group (GBSG) conducted a prospective multicenter trial on the treatment of pT1 pN0 M0 breast carcinoma. Out of 1036 eligible patients from 69 hospitals, a total of 733 underwent breast preservation surgery and postoperative radiotherapy. A detailed quality control (QC) screening of 708 available radiotherapy records was performed by the radiotherapy reference center. The following quality control scoring system was used for all radiotherapy variables: Radiotherapy treatment "completely according to study protocol" (QC score = 0); "acceptable protocol deviations" (QC score = 1); "unacceptable protocol violations" (QC score = 2); the "overall QC score" was the worst judgement for any single quality control criterion, while the "total QC score" was the summation of all single quality control scores (range: 0 to 14). 292 (41.2%) patients were treated per protocol; 290 (41.0%) had acceptable protocol deviations; and 126 (17.8%) had unacceptable protocol violations. 107 (84.9%) single violations, 15 (11.9%) combinations of two, three (2.4%) combinations of three, and one (0.8%) combination of four unacceptable violations were observed. 564 (79.4%) patients achieved a total QC score of < or = 2, 124 (17.5%) of 3 to 5, and 20 (2.8%) of > or = 6. The criterion "radiotherapy treatment duration" had the highest rate of protocol violations, 67/708 (9.5%); other quality control criteria with protocol violations were "radiotherapy reference dose" (27 = 3.8%), "radiotherapy treatment initiation" (15 = 2.1%) and "other protocol violations" (33 = 4.7%). No protocol violations were observed for the criterion "target volume coverage". The protocol compliance improved slightly during the conduct of the study. Institutional differences in protocol compliance were observed depending upon the accrual rate, the institutional treatment preference and between academic and non-academic hospitals. After a short median follow-up of 48 months, differences in protocol compliance, i.e. protocol violations, have not resulted in a reduced disease-free survival; however, the final prognostic evaluation of the quality control review may require longer follow-up and eventually different treatment endpoints to be analyzed.