Soy Protein Supplement In Treating Hot Flashes in Postmenopausal Women Receiving Tamoxifen for Breast Disease

Phase II Study of Soy Protein to Treat Vasomotor Symptoms in Postmenopausal Women Taking Tamoxifen

RATIONALE: Soy protein supplement may be effective in reducing hot flushes in postmenopausal women who are receiving tamoxifen for breast disease.

PURPOSE: Randomized phase II trial to determine the effectiveness of soy protein supplement in reducing hot flushes in postmenopausal women who are receiving tamoxifen for breast disease such as ductal hyperplasia or breast cancer.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to duration of hot flashes (less than 9 months vs 9 months or more) and frequency of hot flashes (7 to 9 per day vs more than 9 per day). For more information regarding the treatment regimens, please see the treatment arms section.

Primary objectives:

1. To compare the effect of daily soy supplementation versus placebo on the daily number of hot flushes experienced by postmenopausal women taking tamoxifen measured at three months from baseline
2. To compare the effect of daily soy supplementation versus placebo on hot flush severity as measured by the average daily hot flash score in this population of women measured at three months from baseline

Secondary objectives:

1. To evaluate the effect of soy supplementation as compared to women randomized to placebo on quality of life as measured by the Medical Outcomes Study (MOS) sleep subscale, the Mental Health Inventory (MHI), the CES-D Short Form, the Menopause and Reproductive Health Questionnaire, and the General Quality of Life Form
2. To measure the effect of soy supplementation as compared to women randomized to placebo on serum isoflavones, estradiol, SHBG, IGF1 and IGFBP3 levels as measures of hormonal change
3. To estimate the effect of daily soy supplementation versus placebo on the time to first relief of hot flushes

A total of 112 patients accrued on this study. Patients were followed 6 months post-randomization.

Eligibility Criteria:

1. Histologic documentation of atypical ductal hyperplasia, ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS), or invasive adenocarcinoma of the breast stages I-III A.

2. Current daily tamoxifen use. Any planned surgery, adjuvant chemotherapy or radiation must have been completed.

3. History of bothersome hot flushes: ≥ 7 hot flushes/day, sufficiently severe that intervention is desired. Participants must have had bothersome hot flushes for at least one month prior to enrollment.

4. Postmenopausal status: surgical menopause, no menses for ≥ 1 year or postmenopausal FSH levels.

5. No concurrent use of vitamin E, progestins (Megace® or others), clonidine, belladonna derivative or commercially available soy supplement preparations for treatment of hot flushes. Participants must have at least a 4-week washout period prior to day 1 of run-in if any of these have been used.

   Participants may be taking low doses of vitamin E that are part of a multivitamin.

6. Concurrent use of anti-depressant, such as Paxil® , Prozac®, or Effexor® is allowed if the participant has been on a stable dose for more than a month and the purpose of the medication is for other than control of hot flushes. If SSRI's are used for hot flashes, they must be discontinued for 4 weeks prior to day 1 of run-in.

7. No concurrent systemic hormone replacement therapy or use of vaginal estrogen creams. Use of the estradiol releasing vaginal ring (Estring®) is allowed.

8. No history of soy or milk intolerance

9. CALGB performance status 0-2