Risedronate in Preventing Bone Loss in Premenopausal Women Receiving Chemotherapy for Primary Breast Cancer

OUTLINE: This is a randomized, placebo-controlled, double-blind study. Patients are stratified according to planned tamoxifen therapy (yes vs no vs undecided), planned taxane therapy (yes vs no vs undecided), time from last menses (1-3 months vs longer than 3 months to 6 months), and age (under 40 vs 40 to 49 vs 50 and over). Patients are randomized to 1 of 2 treatment arms. In both arms, treatment begins during the first month of chemotherapy and continues for 1 year in the absence of unacceptable toxicity. For more information regarding the treatment arms, please see the "Arms" section below. Questionnaires about cessation of menses, ovarian failure, and menopausal symptoms are completed at baseline, monthly during chemotherapy, at 6 months, and then at 1 and 2 years.

Patients are followed for 1 year. A summary of study goals is listed below.

Goals:

• To evaluate the effectiveness of risedronate at a weekly oral dose of 35 mg versus placebo in the prevention of bone loss in premenopausal women undergoing adjuvant or neoadjuvant chemotherapy for primary breast cancer.
• To evaluate the degree of bone loss over one year in premenopausal women undergoing adjuvant chemotherapy for primary breast cancer according to menopausal status at one year after therapy begins.
• To evaluate the relationship of current climacteric symptoms, menstrual and reproductive history, and chemotherapy regimen with ovarian failure (permanent cessation of menses) in premenopausal women undergoing adjuvant or neoadjuvant chemotherapy for primary breast cancer.
• To evaluate the relationship of baseline serum estradiol levels with ovarian failure in premenopausal women undergoing adjuvant or neoadjuvant chemotherapy for primary breast cancer.

• Required Characteristics

• Premenopausal women

• ≤ 6 months since last menstrual period
• no prior bilateral oophorectomy
• not on estrogen replacement therapy
• if TAH is performed, with at least one intact ovary, or if > 3 months since last menstrual period, then patients must have premenopausal estrogen levels ≤ 1 month of study entry
• Scheduled to undergo adjuvant or neoadjuvant chemotherapy for primary breast cancer (stages I-IIIB)
• ≥ 18 years of age
• ECOG performance status (PS) 0 or 1
• Contraindications

• Hypercalcemia (calcium level > 1mg/dL above UNL ≤ 6 months
• Hypocalcemia (calcium level > 0.5 mg/dL below UNL ≤ 6 months
• Inability to stand or sit upright for at least 30 minutes
• Known swallowing disorder
• Bone mineral density T score of ≤ - 2.0 at the hip or lumbar spine

• a patient with a T score of - 2.1 is ineligible
• a patient with a T score of - 1.9 is eligible
• History of vertebral compression fracture

• Exception: traumatic fracture of the coccyx would not exclude a patient from participation
• Corticosteroids at doses > 5 mg daily of prednison or equivalent for > 2 weeks in the past 6 months
• Previous treatment with bisphosphonates
• Diseases affecting bone metabolism (hyperthyroidism, hyperparathyroidism, and hypercortisolism)
• History of severe renal impairment or creatinine > 2.0 mg/dL
• Malabsorption syndrome
• Estrogen replacement therapy
• Oral contraceptive use
• Prior bilateral oophorectomy
• Pregnant women

• Nursing women
• Women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragm, injections, intrauterine device [IUD], surgical sterilization, abstinence, etc.)
• This study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown
• Dental extraction, root canal, or implants ≤ 3 months prior to registration or planned during study treatment