RATIONALE: Hormone replacement therapy may be effective in managing the hot flashes and/or vaginal symptoms in postmenopausal women who are receiving tamoxifen for breast cancer. PURPOSE: Randomized phase III trial to determine the effectiveness of hormone replacement therapy in managing hot flashes and/or vaginal symptoms in postmenopausal women who are receiving tamoxifen for breast cancer.

Condition	Treatment or Intervention	Phase
stage I breast cancer ductal breast carcinoma menopausal symptoms Hot Flashes stage II breast cancer breast cancer in situ	Procedure: supportive care  Behavior: supportive care/therapy  Drug: hot flashes attenuation  Drug: menopausal symptoms attenuation  Drug: conjugated estrogens  Drug: medroxyprogesterone	Phase III

Further Study Details: 

OBJECTIVES: I. Determine the efficacy of hormone replacement therapy in managing hot flashes and menopausal vaginal symptoms in postmenopausal women with a history of node-negative invasive carcinoma or ductal carcinoma in situ of the breast who are receiving adjuvant tamoxifen. II. Determine the effect of this regimen on blood coagulation and lipid profiles in these patients. III. Determine the quality of life of patients treated with this regimen.

PROTOCOL OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to prior hysterectomy (yes vs no), symptom complex (vasomotor vs vaginal vs both), duration of hot flashes (less than 1 year or no hot flashes vs 1 year or more), and average daily number of hot flashes (less than 10 or none vs 10 or more). Patients are randomized to one of two treatment arms. Arm I: Patients who have not undergone prior hysterectomy receive oral medroxyprogesterone once daily for 6 months. If, after 1 month, symptoms do not resolve, patients receive oral conjugated estrogens once daily in addition to medroxyprogesterone for 5 months. Patients who have undergone prior hysterectomy receive oral conjugated estrogens once daily for 6 months. Arm II: Patients receive oral placebo once daily for 6 months. Quality of life is assessed at baseline and months 1, 2, 3, and 6. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 120 patients (60 per treatment arm) will be accrued for this study within 12 months.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed node-negative invasive carcinoma or ductal carcinoma in situ of the breast
• No contralateral breast cancer
• No recurrent or metastatic disease
• Completion of active non-hormonal therapy for breast cancer
• Receiving tamoxifen (20 mg/day) for at least 3 months prior to study and plan to continue drug while on study
• Hot flashes severe enough to seek medical intervention (at least 7-8 moderate to severe hot flashes per day or 60 per week at baseline) AND/OR
• Vaginal symptoms, including dyspareunia, vaginal dryness, irritation, or thinning due to estrogen deficiency
• If uterus present, no prior histologically confirmed adenomatous or atypical endometrial hyperplasia or endometrial carcinoma AND no concurrent endometrial cancer confirmed by pelvic exam within the past year
• No active endometriosis
• No unexplained vaginal bleeding
• Hormone receptor status: Estrogen and progesterone receptor status known for patients with invasive breast cancer

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: Not specified
• Endocrine therapy: See Disease Characteristics; No other concurrent estrogen or hormone replacement therapy; No concurrent clonidine, bellergal, progestational agent, or methyldopa for hot flashes; No concurrent topical vaginal estrogen cream (e.g., Estring or Vagifem) for patients with vaginal symptoms only
• Radiotherapy: Not specified
• Surgery: At least 4 weeks since prior surgery
• Other: At least 12 months since prior treatment for congestive heart failure; Concurrent selective serotonin reuptake inhibitors (SSRI) or antidepressants with SSRI activity allowed if begun at least 3 months prior to study and continue during study

--Patient Characteristics--

• Age: 18 and over
• Sex: Female
• Menopausal status: Postmenopausal; No menstrual period for more than 12 months OR prior bilateral oophorectomy; Must be over 55 years of age OR have documented follicle-stimulating hormone levels in postmenopausal range if one or both ovaries remain after prior hysterectomy
• Performance status: ECOG 0-1
• Life expectancy: Not specified
• Hematopoietic: Not specified
• Hepatic: Not specified
• Renal: Not specified
• Cardiovascular: No prior superficial or deep venous or arterial thrombosis; No serious venous stasis disease
• Pulmonary: No pulmonary embolus
• Other: Must be able to read and speak English; No lower extremity trauma, swelling, or tenderness within the past 4 weeks; No active gallbladder disease; No migraine headaches; No other prior malignancy unless curatively treated with no evidence of recurrence; No concurrent seizure disorder requiring anti-seizure medication

Alabama
      University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham,  Alabama,  35294-3300,  United States
Illinois
      CCOP - Carle Cancer Center, Urbana,  Illinois,  61801,  United States
      CCOP - Central Illinois, Decatur,  Illinois,  62526,  United States
      Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago,  Illinois,  60611-3013,  United States
      Veterans Affairs Medical Center - Lakeside Chicago, Chicago,  Illinois,  60611,  United States
Indiana
      Indiana University Cancer Center, Indianapolis,  Indiana,  46202-5289,  United States
      Veterans Affairs Medical Center - Indianapolis (Roudebush), Indianapolis,  Indiana,  46202,  United States
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States
Michigan
      CCOP - Ann Arbor Regional, Ann Arbor,  Michigan,  48106,  United States
      CCOP - Kalamazoo, Kalamazoo,  Michigan,  49007-3731,  United States
Minnesota
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States
Nebraska
      CCOP - Missouri Valley Cancer Consortium, Omaha,  Nebraska,  68131,  United States
New Jersey
      CCOP - Northern New Jersey, Hackensack,  New Jersey,  07601,  United States
New York
      Albert Einstein Comprehensive Cancer Center, Bronx,  New York,  10461,  United States
North Dakota
      CCOP - Merit Care Hospital, Fargo,  North Dakota,  58122,  United States
Ohio
      Ireland Cancer Center, Cleveland,  Ohio,  44106-5065,  United States
Pennsylvania
      CCOP - MainLine Health, Wynnewood,  Pennsylvania,  19096,  United States
      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111,  United States
      University of Pennsylvania Cancer Center, Philadelphia,  Pennsylvania,  19104-4283,  United States
South Dakota
      CCOP - Sioux Community Cancer Consortium, Sioux Falls,  South Dakota,  57104,  United States
Tennessee
      Vanderbilt-Ingram Cancer Center, Nashville,  Tennessee,  37232-6838,  United States
      Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus, Nashville,  Tennessee,  37212,  United States
Wisconsin
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-6164,  United States
      Veterans Affairs Medical Center - Madison, Madison,  Wisconsin,  53705,  United States

Study chairs or principal investigators

Melody A. Cobleigh,  Study Chair,  Eastern Cooperative Oncology Group   

Study ID Numbers:  CDR0000069015; E-2193; NCI-P01-0194
Record last reviewed:  September 2003
Last Updated:  October 13, 2004
Record first received:  November 9, 2001
ClinicalTrials.gov Identifier:  NCT00026286
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08