Extended Endocrine Therapy for Premenopausal Women With Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: leuprolide; letrozole; zoledronic acid
Intervention description: Given intramuscularly beginning on day 1 and then either 7.5 mg every month or 22.5 mg every 3 months for two years; Taken orally once a day 6-8 weeks after initial leuprolide administration; If desired, given intravenously every 6 months for a total of 4 injections (optional)
Intervention MeSH terms: Zoledronic Acid; Letrozole; Leuprolide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: hormone-receptor positive; tamoxifen; letrozole; zoledronic acid; leuprolide

Summary:

      The purpose of this study is to determine the safety and tolerability of the combination of
      two drugs (letrozole and leuprolide) in women who have already taken tamoxifen for at least
      4.5 years. Letrozole, an aromatase inhibitor (which blocks an enzyme that produces estrogen),
      is a drug that is FDA approved. It has been shown to reduce the risk of breast cancer
      recurrence in postmenopausal women with breast cancer who have been previously treated with
      tamoxifen. Letrozole works by stopping the production of estrogen in parts of the body other
      than the ovaries. Leuprolide is a drug that stops a women's ovarian cycles. This process is
      known as ovarian function suppression. Stopping a women's menstrual cycle may be effective
      against breast cancer for some patients when given as initial therapy. The combination of
      letrozole and leuprolide is considered a standard treatment for women with metastatic breast
      cancer, and is also sometimes used for treatment of premenopausal early stage breast cancer,
      but it has not been accepted as a standard of care treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Women 18 years of age or older

          -  History of invasive ER+ or PR+ breast cancer treated with at least 4.5 years of
             tamoxifen

          -  No current evidence of recurrent invasive disease or metastatic disease. Patients may
             have a history of bilateral breast cancer

          -  Premenopausal (estradiol level in premenopausal range, >20pg/ml, within the prior 28
             days)

          -  Liver function tests and creatinine <2.5 times the upper limit of normal within the 28
             days prior to enrollment

          -  ECOG Performance Status 0-1

          -  Must agree to use non-hormonal contraception (condoms, diaphragm, IUD, sterilization,
             abstinence, etc) and no other hormonal therapy during trial and until 3 months after
             letrozole is stopped

          -  Negative pregnancy test within 14 days prior to enrollment

          -  Patient must be able to speak, read and write in English

        Exclusion Criteria:

          -  Previous treatment with an oral or IV bisphosphonate in the prior two years

          -  History of cancer other than breast cancer within 5 years excluding basal/squamous
             cell skin carcinoma in situ of the cervix

          -  Women with evidence of current local recurrence or metastatic breast cancer

          -  Pregnant women

          -  Nursing women

          -  Women who are currently taking tamoxifen and are unwilling to stop this medication

          -  Women with a known deleterious BRCA 1 or BRCA 2 mutation