Effects of Zometa and Physical Activity on Bone Density in Women Receiving Chemotherapy for Breast Cancer

Background: Breast cancer diagnosis accounts for 32% of all new cancer cases in US women,
with approximately 211,300 women diagnosed in 2003. The majority of these women receive
adjuvant chemotherapy, which may lead to chemotherapy-induced menopause (CIM) in
premenopausal women. CIM often leads to accelerated bone loss, osteopenia, and eventual
osteoporosis.

Purpose: The purpose of this study is to evaluate the effect of zoledronic acid and physical
activity on preventing bone loss in women aged 40 - 55 who are receiving chemotherapy for
breast cancer. The primary objective is to compare the percent change in the lumbar spine
bone mineral density (BMD) from baseline to 12 months for women who are randomized to
either: Group A) intravenous zoledronic acid, oral calcium carbonate, and vitamin D, or
Group B) a prescribed physical activity program, oral calcium carbonate and vitamin D.
Secondary objectives are to compare the percent change between the groups in total hip BMD,
the incidence of vertebral fractures, fatigue, functional status, and other cancer-related
symptoms between the two groups.

Methods: Seventy-two women will be enrolled and randomized to one of two treatment groups.
For participants randomized to Group A, intravenous zoledronic acid will be given every 3
months for the 12 month study period, along with 2 tablets of calcium carbonate (600
mg)/vitamin D (200 IU) daily. For participants randomized to Group B, a physical activity
intervention designed to improve BMD will be prescribed and administered through the
occupational rehabilitation department. Group B participants will also take 2 tablets of
calcium carbonate (600 mg)/vitamin D (200 IU) daily. BMD measurements at the lumbar spine
and hip, and an AP and lateral X-ray will be done at baseline and at 12 months after
enrollment in the study, using dual energy X-ray absorptiometry (DXA). Serum bone-specific
alkaline phosphotase, and N-telopeptide urine tests will be conducted at baseline and 12
months to evaluate bone resorption activity. Other measures that will be assessed via
questionnaires include fatigue (Schwartz Cancer Fatigue Scale), functional status (SF-36), a
4-day food record, and other cancer-related symptoms (MD Anderson Symptom Inventory).

Analysis: Results will be analyzed on an intent-to-treat basis. Descriptive statistics will
be used to analyze demographic data, tumor information, dietary information and baseline
BMD. Differences between baseline means will be analyzed by t-tests. The percent change in
BMD between the two groups will be analyzed by analysis of covariance (ANCOVA). Differences
in other measures will be analyzed by t-tests.

Results: Results of this study will be used to determine if zoledronic acid or physical
activity affect BMD in young women who are receiving chemotherapy for breast cancer.

Inclusion Criteria:

- Women with Stage I - II breast cancer

- Ages 40 - 55

- Pre- or peri-menopausal

- Within 1 month of beginning adjuvant or neoadjuvant chemotherapy

- Baseline lumbar spine and total hip BMD > -2.0 SD

- Able to read and write English

- Signed consent form

Exclusion Criteria:

- Previous treatment with bisphosphonates

- Laboratory evidence of renal disease

- Previous TRAM flap reconstructive surgery

- Positive pregnancy test

- Mental illness that precludes the patient from giving informed consent

- Laboratory evidence of hepatic disease