Anastrozole or Tamoxifen in Treating Postmenopausal Women With Ductal Carcinoma in Situ Who Are Undergoing Lumpectomy and Radiation Therapy

Study Overview
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Brief Summary
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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.

Detailed Description
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OBJECTIVES: Compare the value of anastrozole vs tamoxifen, in terms of preventing recurrence (i.e., local, regional, and distant recurrences and contralateral breast cancer), after lumpectomy and radiotherapy in postmenopausal women with ductal carcinoma in situ (DCIS). Compare subsequent disease occurrence, in terms of invasive breast cancer (local, regional, distant, or contralateral), ipsilateral and contralateral breast cancer (invasive and DCIS), and non-breast second primary malignancies, in patients treated with these drugs. Compare quality of life and symptoms of patients treated with these drugs.* Compare quality-adjusted survival time of patients treated with these drugs.* Compare the occurrence of osteoporotic fractures in patients treated with these drugs. Compare disease-free and overall survival of patients treated with these drugs. NOTE: *The quality of life study closed to accrual as of 12/28/04. OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to age (under 60 vs 60 and over). Patients are randomized to 1 of 2 treatment arms (arm I and arm II closed to accrual as of 6/15/06). Arm I (closed to accrual as of 6/15/06): Patients receive oral tamoxifen and oral placebo once daily for 5 years. Arm II (closed to accrual as of 6/15/06): Patients receive oral anastrozole and oral placebo once daily for 5 years. Beginning within 8 weeks of randomization, all patients also undergo whole breast radiotherapy, unless the patient is enrolled in protocol NSABP-B-39 and randomized to the partial breast irradiation group. Patients are followed every 6 months for 5 years, and then annually thereafter. For patients enrolled in the quality of life study, quality of life is assessed at baseline and then every 6 months for 6 years.* NOTE: *The quality of life study closed to accrual as of 12/28/04. PROJECTED ACCRUAL: A total of 3,000 patients (1,500 per treatment arm) will be accrued for this study within 5 years (arm I and arm II closed to accrual as of 6/15/06).

Official Title
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A Clinical Trial Comparing Anastrozole With Tamoxifen in Postmenopausal Patients With Ductal Carcinoma in Situ (DCIS) Undergoing Lumpectomy With Radiation Therapy

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: anastrozole
* Drug: tamoxifen citrate
* Radiation: Radiation Therapy


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1<br>tamoxifen 20 mg/day and an anastrozole look-alike placebo for 5 years | Drug: tamoxifen citrate<br>* 20 mg/day and placebo for 5 years<br>Radiation: Radiation Therapy<br>* Adjuvant radiation therapy<br>|
| Experimental: Group 2<br>anastrozole, 1 mg/day and an tamoxifen look-alike placebo for 5 years | Drug: anastrozole<br>* 1 mg/day and placebo for 5 years<br>Radiation: Radiation Therapy<br>* Adjuvant radiation therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Free From Breast Cancer | Percentage of patients free from breast cancer event at 10 years where events include local, regional, or distant recurrence or contralateral breast cancer, invasive or DCIS. | 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Free From Invasive Breast Cancer | Percentage of patients free from an invasive breast cancer event where events include invasive local, regional, or distant recurrence, or contralateral breast cancer, occurring as a first cancer event. Note that this endpoint includes only invasive breast cancers and the primary endpoint includes both invasive and DCIS breast cancers. | 10 years | 
| Percentage of Patients Free From Ipsilateral Recurrence | Percentage of patients free from a breast cancer recurrence in the ipsilateral breast (invasive and DCIS), occurring as a first cancer event. | 10 years | 
| Percentage of Patients Free From Contralateral Breast Cancer | Percentage of patients free from a breast cancer recurrence in the contralateral breast (invasive and DCIS), occurring as a first cancer event. | 10 years | 
| Percentage of Patients Free From Non-breast Secondary Cancer | Percentage of patients free from any non-breast second primary cancer other than squamous or basal cell carcinoma of the skin, carcinoma in situ of the colon, melanoma in situ, or carcinoma in situ of the cervix, occurring as a first cancer event. | 10 years | 
| Percentage of Patients Free From Osteoporotic Fractures | Percentage of patients free from fractures of the hip, spine, and wrist. | 10 years | 
| Percentage of Patients Alive and Disease-free | Percentage of patients free from a disease-free survival event where events include any recurrence, second primary cancer, and death from any cause. Lobular carcinoma in situ (LCIS), basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the colon, melanoma in situ, and cervical carcinoma in situ will not be included as recurrences or second primary cancer. | 10 years | 
| Percentage of Patients Alive (Overall Survival) | Percentage of patients alive. | 10 years | 
| Quality of Life-Short Form 12 (SF-12) Physical Health Component Score | The primary outcome of the QOL substudy was the Medical Outcomes Study-Short Form 12 (SF-12) physical health component scale score. The SF-12 physical score was calculated to have a range of 0-100 and was normalized to have a mean of 50 and a standard deviation of 10 in the general population. Higher scores indicate better health. | 5 years | 
| Quality-adjusted Survival Time | The mean quality-adjusted survival time (in months) in each treatment group, estimated by the Quality-Adjusted Time without Symptoms and Toxicity (Q-TWIST) method. | 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer in situ, ductal breast carcinoma in situ