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| ID | Type | Description | Link |
|---|---|---|---|
| SCTN-BR9401 | |||
| EU-94002 | |||
| UKCCCR-ABC/BR9401 |
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RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using tamoxifen may fight breast cancer by blocking the uptake of estrogen. Chemotherapy uses different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with hormone therapy may kill more tumor cells. It is not yet known which treatment regimen is most effective for breast cancer.
PURPOSE: Randomized phase III trial to compare the effectiveness of tamoxifen with that of ovarian ablation, and/or combination chemotherapy in treating premenopausal women with stage I, stage II, or stage IIIA breast cancer.
OBJECTIVES: I. Compare the potential benefits of adjuvant tamoxifen with or without ovarian suppression and/or cyclophosphamide, methotrexate, and fluorouracil (CMF) in premenopausal women with stage I-IIIA, unilateral, invasive breast cancer.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to nodal status (positive vs negative or unknown) and hospital region. Patients undergo surgical resection with or without local radiotherapy, as appropriate. Radiotherapy begins within 8 weeks after surgery for patients randomized to arm I or III and within 4 weeks after completion of chemotherapy for patients randomized to arm II or IV. Patients are randomized to 1 of 4 treatment arms, preferably within 2 weeks after surgery. Arm I: Beginning within 4 weeks after surgery, patients receive oral tamoxifen daily. Treatment continues for 5 years in the absence of disease progression or unacceptable toxicity. Arm II: Beginning within 4 weeks after surgery, patients receive tamoxifen as in arm I and cyclophosphamide IV, methotrexate IV, and fluorouracil IV (CMF) on day 1. Chemotherapy continues every 3 weeks for 6 courses. Arm III: Beginning within 4 weeks after surgery, patients receive tamoxifen as in arm I and 1 of 3 ovarian suppression regimens, preferably regimen A. Regimen B is the preferred alternative to regimen A. Regimen A: Patients undergo oophorectomy. Regimen B: Patients undergo radiation-induced menopause comprising radiotherapy to the pelvis on days 1-4. Regimen C: Beginning 4 weeks after surgery, patients receive goserelin subcutaneously (SC) or leuprolide SC or intramuscularly on day 1. Treatment continues every 4 weeks for 2 years. Arm IV: Patients receive tamoxifen as in arm I and CMF as in arm II followed within 4 weeks by ovarian suppression as in arm III. Patients are followed every 6 months for 5 years and then annually thereafter.
PROJECTED ACCRUAL: A total of 1,000 patients will be accrued for this study.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| cyclophosphamide | Drug | |||
| fluorouracil | Drug | |||
| goserelin acetate | Drug | |||
| leuprolide acetate | Drug | |||
| methotrexate | Drug | |||
| tamoxifen citrate | Drug | |||
| conventional surgery | Procedure | |||
| laparoscopic surgery |
DISEASE CHARACTERISTICS: Histologically proven unilateral, invasive breast cancer Stage T0-3, N0-1, M0 No carcinoma in situ alone, including Paget's disease of the nipple without underlying invasion No evidence of distant disease, including ipsilateral supraclavicular node enlargement unless proven benign No history of pure carcinoma in situ in either breast Hormone receptor status: Not specified
PATIENT CHARACTERISTICS: Age: 70 and under Sex: Female Menopausal status: Premenopausal, defined by 1 of the following criteria: Last menstrual period less than 1 year before surgery Under age 50 with prior hysterectomy (for nonmalignant reason) without bilateral oophorectomy Under age 50 and on continuous oral contraception If at variance with the above definitions, hormonal assays in the premenopausal range take precedence Performance status: Not specified Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified Other: Not pregnant or nursing No other serious illness No other prior invasive malignancy except adequately treated basal cell or squamous cell skin cancer
PRIOR CONCURRENT THERAPY: Not specified
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| Name | Affiliation | Role |
|---|---|---|
| W.D. George, MD, MS, FRCS | University of Glasgow | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospitals of Leicester | Leicester | England | LE1 5WW | United Kingdom | ||
| Aberdeen Royal Infirmary |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 10663329 | Result | Featherstone C, Harnett AN, Brunt AM. Ultrasound localization of the ovaries for radiation-induced ovarian ablation. Clin Oncol (R Coll Radiol). 1999;11(6):393-7. doi: 10.1053/clon.1999.9090. |
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| Procedure |
| oophorectomy | Procedure |
| radiation therapy | Radiation |
| Aberdeen |
| Scotland |
| AB25 2ZN |
| United Kingdom |
| Ninewells Hospital and Medical School | Dundee | Scotland | DD1 9SY | United Kingdom |
| Western General Hospital | Edinburgh | Scotland | EH4 9NQ | United Kingdom |
| Beatson Oncology Centre | Glasgow | Scotland | G11 6NT | United Kingdom |
| University of Glasgow | Glasgow | Scotland | G61 1BD | United Kingdom |
| Raigmore Hospital | Inverness | Scotland | 1V2 3UJ | United Kingdom |
| Royal Alexandra Hospital | Paisley | Scotland | United Kingdom |
| Ayr Hospital | Ayr | KA6 6DX | United Kingdom |
| Falkirk Royal Infirmary | Falkirk | FK1 5RE | United Kingdom |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| D003520 | Cyclophosphamide |
| D005472 | Fluorouracil |
| D017273 | Goserelin |
| D016729 | Leuprolide |
| D008727 | Methotrexate |
| D013629 | Tamoxifen |
| D010535 | Laparoscopy |
| D010052 | Ovariectomy |
| D011878 | Radiotherapy |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D007987 | Gonadotropin-Releasing Hormone |
| D010906 | Pituitary Hormone-Releasing Hormones |
| D007028 | Hypothalamic Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009842 | Oligopeptides |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |
| D000630 | Aminopterin |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D013267 | Stilbenes |
| D001597 | Benzylidene Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D004724 | Endoscopy |
| D003949 | Diagnostic Techniques, Surgical |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D019060 | Minimally Invasive Surgical Procedures |
| D013514 | Surgical Procedures, Operative |
| D002369 | Castration |
| D013507 | Endocrine Surgical Procedures |
| D013519 | Urogenital Surgical Procedures |
| D013509 | Gynecologic Surgical Procedures |
| D013812 | Therapeutics |
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