Trial of Vaginal Estrogen for Urogenital Symptom Relief in Women on Aromatase Inhibitors

Breast cancers are made of different subtypes but by far the most common characteristic is
their estrogen receptor positivity. Seventy percent of breast cancers are estrogen receptor
positive and therefore responsive to the hormone estrogen, which acts as a stimulus for
growth and survival of the cancer. Studies have repeatedly shown that estrogen deprivation
results in prevention of breast cancer in high-risk women, and reduced recurrence of the
cancer both locally and systemically as well as overall survival improvement in those women.
The majority of women with estrogen sensitive breast cancer are placed on anti-estrogen
therapy to prevent the cancer from returning. Even in menopause, women have estrogen
produced in their bodies. Many parts of a woman's body require estrogen for normal
functioning and reducing the amount of estrogen can affect women significantly in different
ways. Some women have significant symptoms like vaginal dryness, which may result in painful
sexual relations, discomfort, and frequent urinary tract (bladder) infections. Although the
investigators goal is to reduce estrogen to prevent breast cancer from returning, quality of
life (how women feel) matters during treatment which can last 5-10 years. A major question
is: how medications such as Vagifem that are used to treat vaginal symptoms affect the rest
of the body?

This question has not been fully answered and is the reason this study is being done. The
safest topical estrogen, Vagifem, is a commercially available tablet which is placed in the
vagina. Vagifem works well in many women and is considered to be safe. It is used by
gynecologists and cancer doctors in this setting all the time. It is not a new product and
has been on the market for many years. Its effects on other parts of the body have not been
tested. The investigators are poised to help answer this question by hypothesizing the
following:

1. It is impossible to know what impact a given estrogen level has in distant sites, the
investigators will however measure these to see if estrogen levels rise in the blood
when women are treated with vaginal estrogen tablets that are commercially available.
The investigators hypothesize that there will not be any elevation in measurable
estrogen levels using very sensitive assays.

2. The investigators also propose using a topical vaginal estrogen application (one that
is commercially available) while carefully monitoring its' effects locally in the
vagina and its possible impact on bone health. The investigators expect women to have
improved vaginal exams as well as improvement in overall quality of life with this
treatment. It is also expected that there will be no impact on bone turnover by this
topical estrogen replacement.

Postmenopausal women on aromatase inhibitors interested in study participation will be asked
to participate for a three month period.

Inclusion Criteria:

1. Treatment of Urogenital symptoms with Vagifem, as deemed appropriate by the treating
physician

2. History of breast cancer stages 0-III

3. Currently being treated with Aromatase Inhibitors (brand not restrictive) for 3
months or longer

4. Postmenopausal women including those with medically induced menopause

5. Urogenital symptoms consistent with vaginal atrophy.

6. Age 18 years or greater

7. Able to participate in informed consent process

8. Able to read/speak English

9. Able to take daily doses of Vitamin D and Calcium

Exclusion Criteria:

1. Abnormal or unexplained uterine bleeding

2. Unable to give informed consent