Red Clover and Lifestyle Changes to Contrast Menopausal Symptoms in Premenopausal Breast Cancer Patients Given Tamoxifen

Study Overview
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Brief Summary
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A prospective double-blind randomized trial of red clover extract (Promensil) vs placebo in surgically-treated premenopausal women with estrogen receptor-positive breast cancer taking tamoxifen

Detailed Description
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Premenopausal women with ER-positive breast cancer treated by surgery and receiving postoperative tamoxifen with or without LHRH analogues, who may have received pre or postoperative chemotherapy, or immunotherapy (for HER2-positive disease), are recruited to a double-blind randomized clinical trial, to receive either a dry extract of red clover (Promensil) as one tablet/day orally containing 80 mg isoflavones (treatment group), or one oral tablet/day without active principle (placebo group) for 24 months. All patients receive a diet-lifestyle intervention involving meetings with a dietician (physician) scheduled once a month for the first 6 months, and every 3 months thereafter. The dietician encourages patients to adhere to a macronutrient-balanced, low glycaemic load Mediterranean-type diet with personalized recommendations to increase intakes of unrefined cereals, pulses, vegetables, unrefined vegetable fats (e.g. olive oil, nuts, oil-containing seeds), and fish, and reduce intake of high-glycaemic-index foods and saturated animal fats. Patients are also encouraged to undertake regular physical activity. Outcomes are Menopausal Rating Score (MRS), body mass index (BMI), waist and hip girth, insulin resistance, and levels of cholesterol, triglycerides, and sex hormones. The safety of the red clover preparation is assessed by pelvic ultrasound and mammograms for endometrial thickness and breast density, and by evaluation of the effects of the serum from treated and placebo patients on ER-positive BC cell lines.

Official Title
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RED CLOVER EXTRACT (PROMENSIL) AND LIFESTYLE CHANGES TO CONTRAST MENOPAUSAL SYMPTOMS IN PREMENOPAUSAL WOMEN WITH HORMONE-SENSITIVE BREAST CANCER RECEIVING ADJUVANT ANTI-ESTROGEN THERAPY

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Promensil
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed operable ER-positive breast cancer Can be ductal carcinoma in situ (DCIS) Absence of locoregional relapse or distant metastasis Normal ovarian function Menopause Rating Score > or equal to 8 Signed informed consent to participate Exclusion Criteria: Menopause Rating Score <8 Menopausal at diagnosis or at surgery Previous malignancies other than in situ cervical carcinoma or non-melanoma skin cancer Breast cancer recurrence Metastatic breast cancer Non-epithelial breast cancer at histological examination In situ lobular breast cancer Participation in other randomized clinical trials that could interfere with current study Living distant from center and unable to attend for check-ups and meetings.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

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
Interventional Model Description: Prospective, randomized, double-blind clinical trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group<br>1 tablet /day of MCE-11 (Promensil) taken orally for 24 months | Drug: Promensil<br>* 1 tablet (80 mg) /day of MCE-11 (Promensil) taken orally for 24 months<br>|
| Placebo Comparator: Placebo group<br>Placebo tablet (without active principle) given once a day for 24 months | Drug: Placebo Oral Tablet<br>* Placebo tablet (80 mg) (without active principle) given once a day for 24 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Menopause Rating Scale (MRS) | Full name of questionnaire is Menopause Rating Scale ; The total score of the MRS ranges between 0 (asymptomatic) and 44 (highest degree of complaints). the ranges are: 0-4 no/little symptoms, 5-8 mild, 9-15 moderate and 16/16+ severe. The sub-scale are: Psychological score, (Question N° 4-7), Somatic score (Question N° 1-3; 11), Urogenital score (Question N° 8-10). The subscales are combined in a total MRS score. | 24 months | 
| weight gain (kg) |  | 24 months | 
| insulin resistance | fasting blood glucose x fasting blood insulin (HOMA-IR) | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| endometrial thickness | assessed by annual pelvic ultrasound (mm) | 24 months | 
| breast density | assessed by annual mammography (BI-RADS) | 24 months | 
| growth of breast cancer cell lines highly expressing estrogen receptors | OD Units | 24 months | 
| transcript expression of estrogen-regulated genes in breast cancer cell lines highly expressing estrogen receptors | transcript levels | 24 months |