Trial Information

The Effects of Zoledronic Acid (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.