RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using tamoxifen may fight breast cancer by blocking the uptake of estrogen. Combination chemotherapy uses different ways to stop tumor cells from dividing so they stop growing or die. Combining hormone therapy with chemotherapy may kill more tumor cells.

PURPOSE: Randomized phase III trial to compare the effectiveness of tamoxifen with or without chemotherapy and/or ovarian ablation in treating women with stage I, stage II, or stage IIIA breast cancer.

OBJECTIVES:

• Estimate overall and relapse-free survival of women with early-stage breast cancer receiving adjuvant tamoxifen with or without adjuvant chemotherapy and/or ovarian suppression.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by participating institution and choice of randomization option.

Postmenopausal women are randomized to the first or second groups.

Randomization for pre- and perimenopausal women is based on the clinician's judgement of appropriate adjuvant therapy (chemotherapy and/or ovarian suppression). Patients may be randomized as follows: among all four groups; for chemotherapy alone (first versus second group); for ovarian suppression alone (first versus third group); for ovarian suppression with nonrandomized assignment to chemotherapy (second versus forth group); for chemotherapy with nonrandomized assignment to ovarian suppression (second versus fourth group).

• First group: Patients receive tamoxifen by mouth every day for 5 years.
• Second group: Patients receive tamoxifen plus cyclophosphamide, methotrexate, fluorouracil (CMF) or doxorubicin/cyclophosphamide (AC). CMF is given every month for 6 courses; AC is given every 3 weeks for 4 courses.
• Third group: Patients receive tamoxifen plus ovarian suppression by oophorectomy, radiation castration, or leuprolide or goserelin.
• Fourth group: Patients receive tamoxifen plus ovarian suppression plus chemotherapy with CMF or AC.

Patients are followed for overall and relapse-free survival.

PROJECTED ACCRUAL: Approximately 6,000 women (4,000 premenopausal, 2,000 postmenopausal) will be accrued for this study.

• Drug: CMF regimen
• Drug: cyclophosphamide
• Drug: doxorubicin hydrochloride
• Drug: fluorouracil
• Drug: goserelin
• Drug: leuprolide acetate
• Drug: methotrexate
• Drug: tamoxifen citrate
• Procedure: oophorectomy
• Radiation: radiation therapy

• Adjuvant Breast Cancer Trials Collaborative Group. Polychemotherapy for early breast cancer: results from the international adjuvant breast cancer chemotherapy randomized trial. J Natl Cancer Inst. 2007 Apr 4;99(7):506-15.
• Adjuvant Breast Cancer Trials Collaborative Group. Ovarian ablation or suppression in premenopausal early breast cancer: results from the international adjuvant breast cancer ovarian ablation or suppression randomized trial. J Natl Cancer Inst. 2007 Apr 4;99(7):516-25.
• Perren TJ. Adjuvant therapy for operable breast cancer; more answers, new questions. Br J Cancer. 1995 Jun;71(6):1142-4. Review. No abstract available.
• Brunt AM. The UKCCCR adjuvant breast cancer (ABC) trial. ABC Trial Steering Committee. Clin Oncol (R Coll Radiol). 1994;6(4):209-10. No abstract available.
• Yarnold JR, Bliss JM, Brunt M, Earl H, Kaye S, Mason M, Mossman J, Perren T, Richards M. Management of breast cancer. Refer women to multidisciplinary breast clinics. BMJ. 1994 Mar 12;308(6930):714-5. No abstract available.
• Bliss JM, Yarnold JR. Treatment of early breast cancer. Lancet. 1992 Apr 11;339(8798):936. No abstract available.

DISEASE CHARACTERISTICS:

• Histologically confirmed invasive carcinoma of the breast for which adjuvant systemic therapy is appropriate

  • Stage I, II, or IIIA
  • Pathologically positive or negative nodes
  • Any size primary tumor
• No edema, peau d'orange, infiltration of the skin, or direct extension to the chest wall

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age:

• Not specified

Sex:

• Female

Menopausal status:

• Pre-, peri-, or postmenopausal

Performance status:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Other:

• No prior malignancy except:

  • Basal cell carcinoma
  • Carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics

Chemotherapy:

• See Disease Characteristics

Endocrine therapy:

• See Disease Characteristics

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• No prior systemic treatment for breast cancer

• Cancer Research Campaign Clinical Trials Centre
• Scottish Cancer Therapy Network
• Yorkshire Regional Clinical Trials Research Unit