Anastrozole or Tamoxifen in Treating Postmenopausal Women With Ductal Carcinoma in Situ Who Are Undergoing Lumpectomy and Radiation Therapy
Condition: Breast Cancer
MeSH terms: Carcinoma; Carcinoma in Situ; Carcinoma, Ductal; Carcinoma, Intraductal, Noninfiltrating
Intervention: anastrozole; tamoxifen citrate; Radiation Therapy
Intervention description: 1 mg/day and placebo for 5 years; 20 mg/day and placebo for 5 years; Adjuvant radiation therapy
Intervention MeSH terms: Tamoxifen; Anastrozole
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 3104.0
Sex: Female
Healthy volunteers: No
Keywords: breast cancer in situ; ductal breast carcinoma in situ

Summary:

      RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Tamoxifen may fight
      breast cancer by blocking the use of estrogen. Anastrozole may fight breast cancer by
      decreasing estrogen production. It is not yet known whether anastrozole is more effective
      than tamoxifen in preventing the recurrence of breast cancer.

      PURPOSE: This randomized phase III trial is studying anastrozole to see how well it works
      compared to tamoxifen in preventing the recurrence of breast cancer in postmenopausal women
      with ductal carcinoma in situ who are undergoing lumpectomy and radiation therapy.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed ductal carcinoma in situ (DCIS) of the breast

               -  Mixed DCIS and lobular carcinoma in situ (LCIS) allowed

          -  Must have undergone lumpectomy

               -  Margins must be histologically free of disease

               -  Re-excision to obtain tumor-free margins allowed

               -  No more than 84 days since prior lumpectomy or re-excision

          -  More than 1 area of DCIS allowed provided all disease is removed with tumor-free
             margins

               -  Masses or clusters of calcification that are clinically or mammographically
                  suspicious must be biopsied

          -  No prior invasive breast cancer or DCIS

               -  Patients with a history of LCIS are eligible

          -  No prior or concurrent invasive (including microinvasive) breast cancer

               -  DCIS "suspicious" for microinvasion allowed

          -  No bilateral malignancy

               -  No mass or mammographic abnormality suspicious for malignancy in the opposite
                  breast unless not malignant as proven by biopsy

          -  No Paget's disease of the nipple

          -  No positive ipsilateral axillary or intramammary nodes

               -  No palpable nodes in the ipsilateral or contralateral axilla or palpable
                  supraclavicular or infraclavicular nodes unless not involved with tumor as proven
                  by biopsy

          -  Hormone receptor status:

               -  Estrogen- or progesterone-receptor positive as determined by immunohistochemistry

                    -  Borderline results are considered positive

        PATIENT CHARACTERISTICS:

        Age

          -  See Menopausal status

        Sex:

          -  Female

        Menopausal status:

          -  Postmenopausal as defined by at least 1 of the following:

               -  Prior documented bilateral oophorectomy

               -  At least 12 months without spontaneous bleeding

               -  Age 55 or over with prior hysterectomy without oophorectomy

               -  Age 54 or under with prior hysterectomy without oophorectomy with a documented
                  follicle-stimulating hormone level in the postmenopausal range

        Performance status

          -  Zubrod 0-2

        Life expectancy

          -  At least 10 years (excluding diagnosis of breast cancer)

        Hematopoietic

          -  WBC normal

        Hepatic

          -  AST normal

          -  Bilirubin normal

          -  Alkaline phosphatase normal

          -  No hepatic disease that would preclude administration of study drugs

        Renal

          -  Creatinine normal

          -  No renal disease that would preclude administration of study drugs

        Cardiovascular

          -  No prior documented cerebral vascular accident or transient ischemic attack

          -  No prior deep vein thrombosis

          -  No cardiovascular disease that would preclude administration of study drugs

          -  No uncontrolled hypertension (i.e., systolic blood pressure at least 180 mm Hg or
             diastolic blood pressure at least 110 mm Hg based on the average of 2 or more readings
             at each of 2 or more visits after initial screening)

          -  No uncontrolled atrial fibrillation

        Pulmonary

          -  No pulmonary embolus

        Other

          -  Not pregnant or nursing

          -  Patients with a history of non-breast malignancies are eligible provided they have
             been disease-free for ≥ 5 years and are deemed by their physician to be at low risk
             for recurrence

          -  No other malignancy within the past 5 years except treated basal cell or squamous cell
             skin cancer, carcinoma in situ of the cervix, carcinoma in situ of the colon, or
             melanoma in situ

          -  No psychiatric or addictive disorders that would preclude informed consent

          -  No uncontrolled diabetes, defined as hemoglobin A1C greater than 9% (fasting glucose
             200 mg/dL)

          -  No nonmalignant systemic disease that would preclude administration of study drugs

        PRIOR CONCURRENT THERAPY:

        Endocrine therapy

          -  No prior or concurrent aromatase inhibitors (e.g., exemestane or letrozole) or
             tamoxifen

          -  No concurrent raloxifene or other selective estrogen receptor modulators

          -  No concurrent sex hormone therapy (e.g., estrogen or progesterone replacement therapy,
             oral contraceptives, androgens, luteinizing hormone releasing hormone analogs,
             prolactin inhibitors, or antiandrogens)

               -  Low-dose estrogen vaginal creams or Estring allowed

        Radiotherapy

          -  Radiotherapy for this cancer initiated before study is allowed

        Surgery

          -  See Disease Characteristics

          -  No prior or concurrent mastectomy for DCIS

          -  Prior sentinel node biopsy or axillary node dissection allowed provided nodes are
             pathologically negative

        Other

          -  No concurrent warfarin

          -  No other systemic therapy for this cancer initiated before study

          -  No other concurrent anticancer therapy unless permitted by the protocol investigator

          -  No concurrent participation in another clinical trial of therapy for DCIS

               -  Concurrent participation in protocol NSABP-B-39 allowed