Hormone Replacement Therapy for Hot Flashes and/or Vaginal Symptoms in Postmenopausal Women Receiving Tamoxifen for Breast Cancer

A Phase III Prospective, Randomized, Double-Blind Clinical Trial of Hormone Replacement Therapy In Postmenopausal Women With A History Of Node-Negative Or Ductal Carcinoma In Situ Who Are Receiving Adjuvant Tamoxifen

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.

OBJECTIVES:

• 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.
• Determine the effect of this regimen on blood coagulation and lipid profiles in these patients.
• Determine the quality of life of patients treated with this regimen.

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.

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

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

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