Peter Steindorfer

Randomized Adjuvant Trial of Tamoxifen and Goserelin Versus Cyclophosphamide, Methotrexate, and Fluorouracil: Evidence for the Superiority of Treatment With Endocrine Blockade in Premenopausal Patients With Hormone-Responsive Breast Cancer—Austrian Breast and Colorectal Cancer Study Group Trial 5

PURPOSE Effective adjuvant treatment modalities in premenopausal breast cancer patients today include chemotherapy, ovariectomy, and tamoxifen administration. The purpose of Austrian Breast and Colorectal Cancer Study Group Trial 5 was to compare the efficacy of a combination endocrine treatment with standard chemotherapy. PATIENTS AND METHODS Assessable trial subjects (N = 1,034) presenting with hormone-responsive disease were randomized to receive either 3 years of goserelin plus 5 years of tamoxifen or six cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF). Stratification criteria included tumor stage and grade, number of involved nodes, type of surgery, and steroid hormone receptor content. Relapse-free survival (RFS) was defined as time from randomization to first relapse, local recurrence, or contralateral incidence, and overall survival (OS) as time to date of death. RESULTS With a 60-month median follow-up, 17.2% of patients in the endocrine group and 20.8% undergoing chemotherapy developed relapses. Local recurrences emerged in 4.7% and 8.0%, respectively. RFS and local recurrence-free survival differed significantly in favor of endocrine therapy (P =.037 and P =.015), with a similar trend observed in OS (P =.195). CONCLUSION Overall, our data suggest that the goserelin-tamoxifen combination is significantly more effective than CMF in the adjuvant treatment of premenopausal patients with stage I and II breast cancer.

Randomized trial of tamoxifen versus tamoxifen plus aminoglutethimide as adjuvant treatment in postmenopausal breast cancer patients with hormone receptor-positive disease: Austrian breast and colorectal cancer study group trial 6.

PURPOSE To determine whether the addition of aminoglutethimide to tamoxifen is able to improve the outcome in postmenopausal patients with hormone receptor-positive, early-stage breast cancer. PATIENTS AND METHODS A total of 2,021 postmenopausal women were randomly assigned to receive either tamoxifen for 5 years alone or tamoxifen in combination with aminoglutethimide (500 mg/d) for the first 2 years of treatment. Tamoxifen was administered at 40 mg/d for the first 2 years and at 20 mg/d for 3 years. RESULTS All randomized and eligible patients were included in the analysis according to the intention-to-treat principle. After a median follow-up of 5.3 years, the 5-year disease-free survival in the aminoglutethimide plus tamoxifen group was 83.6% versus 83.7% in the monotherapy group (P =.89). The corresponding data for overall survival at 5 years were 91.4% and 91.2%, respectively (P =.74). More patients failed to complete combination treatment (13.7%) because of side effects as compared to tamoxifen alone (5.2%; P =.0001). CONCLUSION Aminoglutethimide given for 2 years in addition to tamoxifen for 5 years does not improve the prognosis of postmenopausal patients with receptor-positive, lymph node-negative or lymph node-positive breast cancer.

Hemostatic Methods for the Management of Spleen and Liver Injuries

Abstract. The spleen and liver are the most frequently injured organs during blunt and penetrating abdominal trauma. Emergency laparotomy is crucial for early control of bleeding and to prevent “secondary” injury as a result of physiologic splanchnic vasoconstriction and free oxygen radicals. Altogether 98 patients with spleen and liver injuries were treated over an 8-year period. Primary orthotopic spleen preservation could be achieved in 46 of 63 patients. In 58 patients with hepatic trauma, hemostatic treatment was chosen based on the severity of the injury. Nonoperative management was used for four splenic and seven hepatic trauma patients. The most commonly used techniques were fibrin sealing, suturing, and débridement for hepatic injury and mesh splenorrhaphy, fibrin glue, and partial resection with a TA stapler for splenic injury. The death of patients with complex injuries was mainly due to preclinical massive blood loss and multiple organ failure.

Randomized Trial of Low-Dose Chemotherapy Added to Tamoxifen in Patients With Receptor-Positive and Lymph Node–Positive Breast Cancer

PURPOSE To evaluate the outcome in patients with stage II hormone receptor-positive breast cancer treated or not treated with low-dose, short-term chemotherapy in addition to tamoxifen in terms of disease-free and overall survival. PATIENTS AND METHODS A total of 613 patients were randomized to receive either low-dose chemotherapy (doxorubicin 20 mg/m(2) and vincristine 1 mg/m(2) on day 1; cyclophosphamide 300 mg/m(2); methotrexate 25 mg/m(2); and fluorouracil 600 mg/m(2) on days 29 and 36 intravenously) or no chemotherapy in addition to 20 mg of tamoxifen orally for 2 years. A third group without any treatment (postmenopausal patients only) was terminated after the accrual of 79 patients due to ethical reasons. RESULTS After a median follow-up period of 7.5 years, the addition of chemotherapy did not improve the outcome in patients as compared with those treated with tamoxifen alone, neither with respect to disease-free nor overall survival. Multivariate analysis of prognostic factors for disease-free survival revealed menopausal status, in addition to nodal status, progesterone receptor, and histologic grade as significant. Both untreated postmenopausal and tamoxifen-treated premenopausal patients showed identical prognoses significantly inferior to the tamoxifen-treated postmenopausal cohort. Prognostic factors for overall survival in the multivariate analysis showed nodal and tumor stage, tumor grade, and hormone receptor level as significant. CONCLUSION Low-dose chemotherapy in addition to tamoxifen does not improve the prognosis of stage II breast cancer patients with hormone-responsive tumors. Tamoxifen-treated postmenopausal patients show a significantly better prognosis than premenopausal patients, favoring the hypothesis of a more pronounced effect of tamoxifen in the older age groups.

Significant Increase in Breast Conservation in 16 Years of Trials Conducted by the Austrian Breast & Colorectal Cancer Study Group

ObjectiveTo confirm evidence that breast-conserving treatment (BCT) does not impair the prognosis in breast cancer patients as compared to mastectomy and to argue that it be regarded as the treatment of choice in stage I and II disease. Summary Background DataScientifically, survival rates in breast cancer have been shown to be stage-dependent, but independent of the extent of surgical breast tissue removal, as long as the resection margins are free of tumor infiltration. MethodsBetween 1984 and 1997, six different trials conducted by the Austrian Breast & Colorectal Cancer Study Group accrued a total of 4,259 women with hormone-responsive disease. The authors selected and compared three patient groups (n = 3,316) according to pathologic stage, age, and the surgical procedure applied. ResultsOver this interval, the BCT rate in the premenopausal node-positive subgroup experienced a highly significant increase from 27.2% to 73.2% overall. In the group of postmenopausal node-negative patients, the BCT rate grew significantly by 37.3% to 77.3% in total. With an overall BCT rate growing from 22.5% to 56.8% in postmenopausal node-positive women, those presenting with T1 tumors saw a significant increase from 35.1% to 65.9%. Mortality and local recurrence rates proved stable or even decreased considerably over time and in all subgroups. ConclusionsThe presented outcome of BCT rates, significantly improved over this 16-year period and in no way counterbalanced by higher local recurrence or death rates, reflects an excellent example of surgical quality control. BCT can safely be regarded as the standard of therapy for T1 and increasingly for T2 disease. Especially in multi-institutional adjuvant breast cancer trials, the highest priority should be given to breast-conserving procedures.

Very Low-dose Adjuvant Chemotherapy in Steroid Receptor Negative Stage I Breast Cancer Patients

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

4′-O-Tetrahydropyranyl-doxorubicin in advanced breast cancer: a phase II study

SummaryIn a phase II study, 35 patients with advanced breast cancer were treated with 4′-O-tetrahydropyranyldoxorubicin (THP-DXR) (70 mg/m2 i.v. on day 1); treatment was repeated every 3 weeks. Eight patients had failed prior chemotherapy for advanced disease. A total of 34 patients were evaluable for response. After a median of 10 treatment courses (range, 3–15), objective tumor response was seen in 59% (20 of 34 patients) (95% confidence limits, 42%–75%). In all, 17 partial remissions and 3 complete remissions were observed; stable disease occurred in 13 patients. The median duration of response was 42+ weeks (range, 21–77+ weeks). The dose-limiting side effects were leukopenia (26 patients, WHO grade III–IV) and thrombocytopenia (9 patients, WHO grade II–IV). Nausea/vomiting was experienced by 34 patients; in 18, it reached WHO grade II–III. Other treatment-related side effects included alopecia (WHO grade II–III) in 26 patients and stomatitis and diarrhea (WHO grade I–III) in 9 patients. At cumulative doses of THP-DXR of at least 700 mg/m2 (range, 700–1,050 mg/m2), no signs of congestive heart failure were observed. We conclude that THP-DXR is effective for first- and second-line chemotherapy in advanced breast cancer and that side effects are manageable.

Malignes schwannom der Mamma

Das maligne Schwannom (MS) stellt einen Tumor der Schwannschen oder Nervenscheidenzellen dar, der am hdufigsten im Bereich der unteren und oberen Extremitat, Stamm and Kopfregion auftritt. Wir berichten uber den dritten Fall eines in der Mamma lokalisierten MS. Der tastbare, 1,2 cm im Durchmesser grose Tumor fand sich im oberen inneren Quadranten der rechten Brust einer 27j dhrigen Fran. Nach sonographischer und mammographischer Darstellung, sowie Feinnadelbiopsie wurde der Tumor chirurgisch entfernt.Malignant schwannoma (MS) is a tumor of the Schwann or nerve sheath cells, most frequently occurring in the lower and upper extremities, trunk and head region. We report the third known case of MS of the breast, which occurred in a 27-year-old woman. The palpable tumor, about 1.2 cm in diameter, was localized in the upper inner quadrant of the right breast. After ultrasonography, mammography and fine needle aspiration cytology, the tumor was removed surgically.ZusammenfassungDas maligne Schwannom (MS) stellt einen Tumor der Schwannschen oder Nervenscheidenzellen dar, der am hdufigsten im Bereich der unteren und oberen Extremität, Stamm and Kopfregion auftritt. Wir berichten über den dritten Fall eines in der Mamma lokalisierten MS. Der tastbare, 1,2 cm im Durchmesser große Tumor fand sich im oberen inneren Quadranten der rechten Brust einer 27j dhrigen Fran. Nach sonographischer und mammographischer Darstellung, sowie Feinnadelbiopsie wurde der Tumor chirurgisch entfernt.

Abgeschlossene und derzeit laufende adjuvante Therapieprotokolle bei Patientinnen mit operablem Mammakarzinom (II)

Background: Between 1984 and 1996 4336 patients with operated breast cancer were included in trials of the Austrian breast cancer study group.ZusammenfassungGrundlagen: Seit 1984 wurden 4336 Patientinnen mit Mammakarzinom österreichweit in adjuvante Therapiestudien eingebracht. Methodik: Basierend auf Prognosefaktoren, wurden Patientinnen nach 2 Therapiearten randomisiert. Ergebnisse: Die größte, jemals in Österreich durchgeführte Studie bei postmenopausalen Patientinnen wurde bereits abgeschlossen. 5 weitere Studien sind offen für die Randomisierung. Schlußfolgerungen: Der Ansatz, Studien österreichweit anzubieten und einheitliche Studienkonzepte zu bewerben, ist außerordentlich erfolgversprechend und muß weiter verfolgt werden.SummaryBackground: Between 1984 and 1996 4336 patients with operated breast cancer were included in trials of the Austrian breast cancer study group. Methods: Based on prognostic factors patients were randomised with 2 different treatment groups. Results: The largest ever performed oncological trial (study VI) in postmenopausal breast cancer patients is already finished. 5 other trials are open for randomisation. Conclusions: It is the intention of the Austrian breast cancer study group to accrue patients for ongoing trials in whole Austria and to increase the number of randomised patients.

Randomised Trial: One Cycle of Anthracycline-Containing Adjuvant Chemotherapy Compared with Six Cycles of CMF Treatment in Node-Positive, Hormone Receptor-Negative Breast Cancer Patients

Aim: A randomised, controlled clinical trial was initiated in 1984 to test whether 1 cycle of anthracycline-containing adjuvant chemotherapy improves the outcome of breast cancer patients presenting with stage II disease and negative oestrogen and progesterone receptors (ER, PgR), as compared with 6 cycles of dose-reduced CMF. Patients and Methods: Within 7 years 263 women with stage II breast cancer were randomised either to receive 1 cycle of doxorubicin, vinblastine, cyclophosphamide, methotrexate and 5- fluorouracil (AV-CMF) or to receive 6 cycles of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Patients were stratified for tumour stage, nodal stage, menopausal status, type of surgery and participating centre. Results: After a median follow-up of 100 months, neither disease-free (DFS) nor overall survival (OS) differed significantly between the two groups. Conclusions: Compared to 6 cycles of a non-standard low-dose CMF regimen 1 cycle of anthracycline- containing adjuvant chemotherapy failed to improve the outcome in women with stage II receptor-negative breast cancer in terms of DFS and OS.