Estradiol Levels in Patients Treated With Estring

Study Overview
=================
Brief Summary
-----------------
Estrogen receptor positive breast cancer is the most common type of breast cancer and anti-estrogen therapy has been shown to be very effective in preventing recurrence. Side effects of anti-estrogens are due to estrogen deprivation and include hot flashes, mood changes and vaginal dryness/pain. Vaginal symptoms including pain, dryness, itching, bleeding after intercourse and frequent urinary tract infections have been reported to cause significant morbidity in postmenopausal women and higher in breast cancer survivors on anti-estrogen therapy. Treatment options include vaginal lubricants, Replens etc but unfortunately many women continue to have persistent symptoms. Local estrogen has been shown to be effective in post menopausal women (Estring or Vagifem) for their vaginal symptoms. There is a concern of using this in women with breast cancer given it may increase their blood estrogen levels. Studies done so far show have shown controversial results but majority of them report that blood estrogen levels do not change significantly. The major drawback of the studies was the sample size and inadequate accrual. The most recent trial reported showed no significant change in blood estrogen levels in women with breast cancer treated with aromatase inhibitors (anti-estrogen therapy) and were on vagifem for their vaginal symptoms. The authors reported results in 26 patients and reported no significant change in blood estrogen level. We propose to study the change in blood estrogen level when postmenopausal women with breast cancer who are currently on aromatase inhibitors are treated with Estring for their vaginal symptoms.

Official Title
-----------------
A Single-arm Phase II Trial to Evaluate Serum Estradiol Levels in Patients With Breast Cancer Treated With Vaginal Estrogen, Estring

Conditions
-----------------
Estrogen Levels Among Breast Cancer Patients

Intervention / Treatment
-----------------
* Drug: Estradiol


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Stage I-III estrogen receptor positive breast cancer (positive for estrogen receptor (ER)) with positivity defined as immunohistochemical staining in ≥ 10% of cells) on adjuvant hormonal therapy with aromatase inhibitors (anastrozole, letrozole or exemestane) Adults over 18 years of age with a life expectancy of at least 3 months Attained menopause as defined by World Health Organization Criteria (defined as permanent cessation of menstruation resulting from the loss of ovarian follicular activity. This is recognized to occur after 12 consecutive months of amenorrhea, for which there is no other obvious pathological or physiological cause.) Persistent genitourinary symptoms causing discomfort for more than 2 weeks prior to the visit with the physician. Tried at least 1 prior pharmacological/ non-pharmacological treatment for their genitourinary symptoms Be informed of the investigational nature of this study and provide written informed consent in accordance with institutional and federal guidelines prior to any study specific procedures Be willing and able to comply with the treatment plan, scheduled clinic visits, laboratory tests and other study procedures Exclusion Criteria: Patients with metastatic breast cancer Have a concurrent active non-breast malignancy except for non-melanoma skin cancer Patients with vaginal stenosis Patients unable to apply Estring

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Estradiol<br>ESTRING® (estradiol vaginal ring) is a slightly opaque ring with a whitish core containing a drug reservoir of 2 mg estradiol. Estradiol, silicone polymers and barium sulfate are combined to form the ring. When placed in the vagina, ESTRING releases estradiol, approximately 7.5 mcg per 24 hours, in a consistent stable manner over 90 days. | Drug: Estradiol<br> <br> * Other names: ESTRING®;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Serum Estradiol | To measure changes in serum estradiol level compared to their baseline in patients with breast cancer when treated with vaginal estrogen preparation, Estring | Baseline, 16 weeks |