SWOG-8814 Tamoxifen With or Without Combination Chemotherapy in Postmenopausal Women Who Have Undergone Surgery for Breast Cancer
SWOG-8814 Tamoxifen With or Without Combination Chemotherapy in Postmenopausal Women Who Have Undergone Surgery for Breast Cancer
RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using
 tamoxifen may fight breast cancer by blocking the use of estrogen by the tumor cells. Drugs
 used in chemotherapy, such as doxorubicin, cyclophosphamide, and fluorouracil, work in
 different ways to stop the growth of tumor cells, either by killing the cells or by stopping
 them from dividing. It is not yet known whether giving tamoxifen alone is more effective in
 treating breast cancer than giving tamoxifen together with chemotherapy or after
 chemotherapy.

 PURPOSE: This randomized phase III trial is studying giving tamoxifen with or without
 combination chemotherapy to compare how well they work in treating postmenopausal women who
 have undergone surgery for breast cancer.
OBJECTIVES: I. Compare disease-free survival and overall survival of postmenopausal women
 with node-positive, estrogen and/or progesterone receptor-positive adenocarcinoma of the
 breast randomly assigned to postoperative adjuvant treatment with long-term (5 years)
 tamoxifen vs. CAF (cyclophosphamide/doxorubicin/fluorouracil) plus concurrent and long-term
 tamoxifen vs. CAF followed by long-term tamoxifen. II. Compare the relative toxicities of
 these three regimens.

 OUTLINE: Randomized study. All patients are randomized on Arms I, II, and III. Lumpectomy
 patients must receive radiotherapy on Regimen A. At the discretion of the physician,
 mastectomy patients may receive radiotherapy on Regimen B for a tumor greater than 5 cm in
 diameter, 4 or more positive nodes, or extranodal extension of the tumor into the axillary
 fat. Patients randomized to Arm I who are to receive radiotherapy should begin as soon as
 feasible postoperatively; these patients may be irradiated while receiving tamoxifen.
 Patients on Arms II and III who are to receive radiotherapy are treated either
 postoperatively prior to registration or after completion of and recovery from 6 courses of
 CAF. Arm I: Antiestrogen Therapy. Tamoxifen, TMX, NSC-180973. Arm II: 3-Drug Combination
 Chemotherapy followed by Antiestrogen Therapy. CAF: Cyclophosphamide, CTX, NSC-26271;
 Doxorubicin, DOX, NSC-123127; Fluorouracil, 5-FU, NSC-19893; followed by TMX. Arm III: 3-Drug
 Combination Chemotherapy plus Concurrent Antiestrogen Therapy. CAF; plus concurrent TMX.
 Regimen A: Radiotherapy. Irradiation of the breast and underlying chest wall and (optionally)
 of the supraclavicular area and, if indicated, the axilla, using megavoltage equipment with
 photon energies of up to 6 MV followed, if indicated, by a tumor bed boost using either
 electrons or iridium-192 (192-Ir) implants. Regimen B: Radiotherapy. Irradiation of the chest
 wall using either megavoltage photons via a tangential field or electrons via a direct field
 plus (optional) photon irradiation of the supraclavicular area and, if indicated, the axilla.

 PROJECTED ACCRUAL: 350 patients will be randomized to Arm I and 530 patients each will be
 randomized to Arms II and III. Accrual should be completed in about 4 years, and 4 additional
 years will be required for follow-up.
DISEASE CHARACTERISTICS: Histologically proven adenocarcinoma of the breast No apocrine,
 adenoidcystic, or squamous carcinomas or sarcomas Pathologic Stage T1-3a, pathologic N1-2
 (clinical N0-1), M0: Rendered free of gross tumor at surgery Primary tumor movable with
 respect to chest wall Axillary nodes movable with respect to chest wall and each other No
 preoperative edema of the arm, peau d'orange, skin ulceration, or inflammatory lesions One
 or more positive lymph nodes required No positive deep mastectomy margins or clinical skin
 involvement (focal microscopic dermal invasion or focal microscopic dermal lymphatic
 involvement allowed) No evidence of metastatic disease on pretherapy studies (including
 chest x-ray, bone scan, and mammogram) No bilateral invasive tumors Patients who had
 noninvasive ductal carcinoma in situ of the opposite breast and underwent prophylactic
 contralateral mastectomy are eligible Hormone receptor status: Positive for estrogen and/or
 progesterone receptors (at least 10 fmol/mg protein or unequivocally positive
 immunocytochemical assay for one or both) Participation in SWOG-8854 (flow cytometry)
 recommended

 PATIENT CHARACTERISTICS: Age: Any age Sex: Females only Menopausal status: Postmenopausal
 as defined by 1 or more of the following: Bilateral oophorectomy at least 2 months prior to
 diagnosis of breast cancer (with or without estrogen therapy following surgery) Prior
 hysterectomy with at least 1 ovary remaining and either over 60 years old or with a
 postmenopausal FSH level Natural menopause (last menstrual period at least 1 year prior to
 registration or 4-12 months prior to registration with a postmenopausal FSH level) Treated
 with postmenopausal estrogen therapy and either over 55 years old or with a postmenopausal
 FSH level Performance status: Not specified Hematopoietic: WBC at least 3,500/mm3 Platelet
 count at least 100,000/mm3 Hepatic: Bilirubin no more than 1.2 x normal Alkaline
 phosphatase no more than 1.2 x normal SGOT or SGPT no more than 1.2 x normal Renal:
 Creatinine no more than 2.0 mg/dL Cardiovascular: No uncontrolled hypertension No history
 of ischemic heart disease or CHF Normal ejection fraction by MUGA (required only if deemed
 clinically necessary for assessment) Other: No medical condition that would preclude
 protocol therapy: No severe diabetes No active ulcer disease No significant psychiatric
 disease No second malignancy within 5 years except: Adequately treated nonmelanomatous skin
 cancer Curatively treated Stage I cervical carcinoma Pretreatment mammogram and chest x-ray
 completed no more than 3 months preoperatively; blood/body fluid analyses to determine
 eligibility completed within 14 days prior to registration; prestudy bone scan completed
 within 12 weeks prior to registration and/or within 4 weeks prior to surgery

 PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior
 chemotherapy Endocrine therapy: No prior hormonal therapy (except for up to 14 days of
 tamoxifen stopped prior to registration) Prior estrogen- and/or progesterone-containing
 hormone preparations for nononcologic therapy allowed, but must be discontinued prior to
 registration Postmenopausal estrogen therapy should be discontinued in all patients at the
 time of diagnosis of breast cancer Radiotherapy: Postoperative chest wall and/or regional
 lymph node irradiation allowed for mastectomy patients (at discretion of the physician)
 either prior to registration or on protocol for any of the following: Tumor greater than 5
 cm in diameter 4 or more positive nodes Extranodal extension of tumor into the axillary fat
 No radiotherapy for any other reason in mastectomy patients Postoperative radiotherapy
 either prior to registration, during tamoxifen, or after completion of chemotherapy
 required for lumpectomy patients Radiotherapy must be completed (if it is to be given
 before chemotherapy) prior to registration No immediate radiotherapy after randomization to
 chemotherapy Surgery: Radical, modified radical, or breast-sparing surgical procedure with
 at least a level I and II axillary dissection and analysis of at least 6 nodes required
 within 12 weeks prior to registration Lumpectomy must include: Total excisional biopsy with
 rim of normal breast tissue Microscopically negative margins Level I and II axillary
 dissection Tumor no more than 5 cm in greatest diameter Clinical and mammographic
 examination demonstrating absence of multicentric lesions Type of surgery, number of nodes
 examined, number of positive nodes, and size of the primary tumor (size of the largest
 tumor if more than 1 mass) must be recorded