Hormone Replacement Therapy for Hot Flashes and/or Vaginal Symptoms in Postmenopausal Women 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