Phase III Study of Adjuvant Therapy in Pre- and Perimenopausal Women with Node-Negative Breast Cancer: Cyclophosphamide/Methotrexate/Fluorouracil (CMF) vs Goserelin vs Sequential CMF and Goserelin
Chemotherapy and Hormone Therapy in Treating Premenopausal or Perimenopausal Women With Node-Negative Breast Cancer
Basic Trial Information
I. Compare relapse rates and survival of node-negative pre- and perimenopausal breast cancer patients randomly assigned to 6 courses of cyclophosphamide/methotrexate/fluorouracil (CMF) followed by 72 weeks of goserelin vs. CMF alone vs. 96 weeks of goserelin alone. II. Evaluate patients' perceptions of well being and coping during adjuvant treatment, following treatment but before relapse, and after relapse.
Stage T1-3, pN0, M0 breast cancer Potentially curatively resected within 6 weeks of entry by one of the following: Total mastectomy Breast-conserving procedure (lumpectomy or quadrantectomy) for tumors less than 5 cm Total mastectomy within 4 weeks of initial surgery required if margins positive after initial surgery Axillary clearance (not sampling) required at surgery, with no evidence of nodal involvement upon examination of at least 8 lymph nodes from ipsilateral axilla Suspicious manifestations of metastatic disease (e.g., hot spots on bone scan) must be proven benign No bilateral breast cancer Masses in contralateral breast must be biopsy-proven to be benign Hormone receptor status: Estrogen receptor positive
Biologic therapy: No prior biologic therapy for breast cancer Chemotherapy: No prior chemotherapy for breast cancer Endocrine therapy: No prior hormonal therapy for breast cancer Radiotherapy: No prior radiotherapy for breast cancer Concurrent radiotherapy allowed for patients with less than total mastectomy Surgery: Potentially curative surgery within 6 weeks of entry required
Age: See Menopausal status Sex: Female Menopausal status: Pre- or perimenopausal, i.e.: Age greater than 52 with last normal menstrual period within 1 year Age 52 or younger with last normal menstrual period within 3 years or currently menstruating Age 55 or younger with hysterectomy that left one functioning ovary Biochemically confirmed ovarian function in questionable cases Performance status: Not specified Hematopoietic: WBC at least 4,000/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin less than 1.1 mg/dL (20 micromoles/L) AST less than 60 IU/L Renal: Creatinine less than 1.3 mg/dL (120 micromoles/L) Other: No nonmalignant systemic disease that would preclude protocol therapy (including lipid metabolism disorders) No psychiatric or addictive disorder that would preclude informed consent No second malignancy except: Nonmelanomatous skin cancer Adequately treated in situ carcinoma of the cervix Not pregnant or nursing (including those who have stopped nursing within the past 6 months)
1,065 evaluable patients will be studied over about 5 years.
This is a randomized study. Patients are stratified by participating institution. Patients with breast conserving surgery are further stratified by whether radiotherapy is planned. Patients in arm I, which closed in March of 1992, were observed without treatment. Patients in arm II receive goserelin every 28 days for 2 years. Patients in arm III receive cyclophosphamide, methotrexate, and fluorouracil (CMF) every 28 days for 6 courses. Patients in arm IV receive CMF as above, followed by goserelin every 28 days for 18 months. Patients who have undergone breast conserving surgery may receive optional radiation therapy, beginning within 3 months of entry for the first and second arms and 2 weeks following the last course of CMF for the third and fourth arms. All patients are followed every 3 months for 1 year, then every 6 months for 2 years, then annually thereafter.
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Viale G, Regan MM, Maiorano E, et al.: Chemoendocrine compared with endocrine adjuvant therapies for node-negative breast cancer: predictive value of centrally reviewed expression of estrogen and progesterone receptors--International Breast Cancer Study Group. J Clin Oncol 26 (9): 1404-10, 2008.[PUBMED Abstract]
Bernhard J, Zahrieh D, Castiglione-Gertsch M, et al.: Adjuvant chemotherapy followed by goserelin compared with either modality alone: the impact on amenorrhea, hot flashes, and quality of life in premenopausal patients--the International Breast Cancer Study Group Trial VIII. J Clin Oncol 25 (3): 263-70, 2007.[PUBMED Abstract]
Castiglione-Gertsch M, O'Neill A, Price KN, et al.: Adjuvant chemotherapy followed by goserelin versus either modality alone for premenopausal lymph node-negative breast cancer: a randomized trial. J Natl Cancer Inst 95 (24): 1833-46, 2003.[PUBMED Abstract]
Castiglione-Gertsch M, O'Neill A, Gelber RD, et al.: Is the addition of adjuvant chemotherapy always necessary in node negative (N-) pre/perimenopausal breast cancer patients (pts) who receive goserelin? First results of IBCSG trial VIII. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-149, 2002.
Coates AS, Millar EK, O'Toole SA, et al.: Prognostic interaction between expression of p53 and estrogen receptor in patients with node-negative breast cancer: results from IBCSG Trials VIII and IX. Breast Cancer Res 14 (6): R143, 2012.[PUBMED Abstract]
Karlsson P, Cole BF, Colleoni M, et al.: Timing of radiotherapy and outcome in patients receiving adjuvant endocrine therapy. Int J Radiat Oncol Biol Phys 80 (2): 398-402, 2011.[PUBMED Abstract]
Colleoni M, Cole BF, Viale G, et al.: Classical cyclophosphamide, methotrexate, and fluorouracil chemotherapy is more effective in triple-negative, node-negative breast cancer: results from two randomized trials of adjuvant chemoendocrine therapy for node-negative breast cancer. J Clin Oncol 28 (18): 2966-73, 2010.[PUBMED Abstract]
Maiorano E, Regan MM, Viale G, et al.: Prognostic and predictive impact of central necrosis and fibrosis in early breast cancer: results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy. Breast Cancer Res Treat 121 (1): 211-8, 2010.[PUBMED Abstract]
Viale G, Giobbie-Hurder A, Gusterson BA, et al.: Adverse prognostic value of peritumoral vascular invasion: is it abrogated by adequate endocrine adjuvant therapy? Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy for early breast cancer. Ann Oncol 21 (2): 245-54, 2010.[PUBMED Abstract]
Zhang JJ, Wang M: Latent class joint model of ovarian function suppression and DFS for premenopausal breast cancer patients. Stat Med 29 (22): 2310-24, 2010.[PUBMED Abstract]
Pestalozzi BC, Zahrieh D, Mallon E, et al.: Distinct clinical and prognostic features of infiltrating lobular carcinoma of the breast: combined results of 15 International Breast Cancer Study Group clinical trials. J Clin Oncol 26 (18): 3006-14, 2008.[PUBMED Abstract]
Ravaioli A, Monti F, Regan MM, et al.: p27 and Skp2 immunoreactivity and its clinical significance with endocrine and chemo-endocrine treatments in node-negative early breast cancer. Ann Oncol 19 (4): 660-8, 2008.[PUBMED Abstract]
Viale G, Regan MM, Mastropasqua MG, et al.: Predictive value of tumor Ki-67 expression in two randomized trials of adjuvant chemoendocrine therapy for node-negative breast cancer. J Natl Cancer Inst 100 (3): 207-12, 2008.[PUBMED Abstract]
Karlsson P, Cole BF, Price KN, et al.: The role of the number of uninvolved lymph nodes in predicting locoregional recurrence in breast cancer. J Clin Oncol 25 (15): 2019-26, 2007.[PUBMED Abstract]
Keshaviah A, Dellapasqua S, Rotmensz N, et al.: CA15-3 and alkaline phosphatase as predictors for breast cancer recurrence: a combined analysis of seven International Breast Cancer Study Group trials. Ann Oncol 18 (4): 701-8, 2007.[PUBMED Abstract]
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Pestalozzi BC, Zahrieh D, Price KN, et al.: Identifying breast cancer patients at risk for Central Nervous System (CNS) metastases in trials of the International Breast Cancer Study Group (IBCSG). Ann Oncol 17 (6): 935-44, 2006.[PUBMED Abstract]
Regan MM, Viale G, Mastropasqua MG, et al.: Re-evaluating adjuvant breast cancer trials: assessing hormone receptor status by immunohistochemical versus extraction assays. J Natl Cancer Inst 98 (21): 1571-81, 2006.[PUBMED Abstract]
Szwarc SE, Bonetti M: Modelling menstrual status during and after adjuvant treatment for breast cancer. Stat Med 25 (20): 3534-47, 2006.[PUBMED Abstract]
Aebi S, Castiglione-Gertsch M: Adjuvant endocrine therapy for the very young patients. Breast 12 (6): 509-15, 2003.[PUBMED Abstract]
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Trial Contact Information
Trial Lead Organizations
International Breast Cancer Study Group
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.