DOUBLE-BLIND RANDOMIZED TRIAL OF TAMOXIFEN VERSUS PLACEBO IN PATIENTS WITH NODE POSITIVE BREAST CANCER WHO HAVE COMPLETED CMF, CEF OR AC ADJUVANT CHEMOTHERAPY

Inclusion Criteria

DISEASE CHARACTERISTICS: Adenocarcinoma of the breast with 1 or more histologically proven
positive axillary nodes OR Adenocarcinoma of the breast with negative axillary nodes or
adverse prognostic factors such that the patient is at high risk for recurrence and node
negative lesion is characterized by the following features: Tumor at least 1 cm Poorly
differentiated, SBR grade III, or MSBR grade V and/or lymphatic/vascular invasion
Pathologic review by experienced breast pathologist recommended if grade is unspecified
and lymphatic/vascular invasion is absent Disease considered potentially curable and
treated by 1 of the following: Complete surgical removal of the breast plus axillary node
dissection Partial surgical removal of the breast plus axillary node dissection, with the
intention of giving breast irradiation following completion of an adjuvant chemotherapy
regimen Regional nodal or chest wall irradiation not prohibited but strongly discouraged
No evidence of residual tumor in the axilla following dissection No microscopic evidence
of residual tumor at the resection margins following total mastectomy Further excision
highly recommended if there is microscopic residual disease present at partial mastectomy
margins If further excision is not undertaken, a radiotherapy boost to the tumor bed is
required in addition to breast irradiation given following protocol chemotherapy Disease
clinically staged prior to surgery as T1-T3a, N0-2, M0 No clinical T4 disease, i.e.: No
extension to the chest wall No edema (including peau d'orange) No skin ulceration No
satellite skin nodules confined to the same breast No inflammatory carcinoma Disease
pathologically staged following surgery as TNM stage I, II, or III (T0-4; N0-2; M0) T4
allowed only with dermal involvement on pathology assessment No evidence of metastatic
disease beyond the homolateral axillary nodes on pre-chemotherapy chest x-ray, bone scan
(with radiographs of suspicious areas), and abdominal ultrasound (required only if
bilirubin, alkaline phosphatase, or AST/ALT are elevated) Simultaneous bilateral breast
carcinoma allowed Complete tumor resection on both breasts required Axillary dissection on
both sides must meet criteria as above if both sides are clinically node-positive Axillary
dissection on the second side optional if the axilla is clinically negative at the time of
surgery and the other side is node-positive Adjuvant chemotherapy must begin within 14
weeks of initial pathologic diagnosis Hormone receptor status: Any receptor level allowed
(values must be available if biochemical method used; immunocytochemical assay permitted)

PATIENT CHARACTERISTICS: Age: Not specified Sex: Female Menopausal status: Pre- or
perimenopausal, i.e., meeting at least 1 of the following criteria: Normal menstruation
Amenorrhea for less than 1 year (up to 3 years in patients under age 52) Biochemical
evidence of ovarian function Hysterectomy without bilateral oophorectomy in patients under
age 56 Premenopausal women no greater than age 50 who were started on replacement hormone
therapy before amenorrhea are eligible Performance status: ECOG 0-2 prior to chemotherapy
Hematopoietic: WBC at least 3,000/mm3 Polymorphs and bands at least 1,500/mm3 Platelet
count at least 100,000/mm3 Hepatic: (unless abdominal ultrasound indicates liver
metastasis) Alkaline phosphatase no greater than 2 times normal AST and/or ALT no greater
than 2 times normal Renal: Not specified Other: No history of serious underlying medical
illness or psychiatric or addictive disorder No second malignancy within 5 years except:
Curatively treated nonmelanomatous skin cancer Curatively treated endometrium, colon, or
thyroid cancer or carcinoma in situ of the cervix No plan for pregnancy during the 5-year
study period Fertile women must use effective contraception (other than oral
contraception) Accessible for treatment and follow-up

PRIOR CONCURRENT THERAPY: Biologic therapy: Colony-stimulating factors allowed (use must
be documented) Chemotherapy: No prior chemotherapy No concurrent other cytotoxic therapy
Endocrine therapy: Adjuvant tamoxifen (20 mg po daily) allowed up to 2 weeks before or
during adjuvant chemotherapy provided drug is discontinued at randomization No long-term
prednisone or other hormones Radiotherapy: See Disease Characteristics Surgery: See
Disease Characteristics