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

• Average intra-patient change in lumbar spine (L2-L4, PA) bone mineral density (BMD) from baseline to one year after study entry
  

• Average intra-patient change in femoral neck and total hip BMD from baseline to one year after study entry
  
• Incidence of osteopenia in the risedronate vs placebo groups at one year after study entry
  
• Incidence of osteoporosis in the risedronate vs placebo groups at one year after study entry
  
• Incidence of a 5% difference in intra-patient BMD scores at baseline
  
• Serum and urine N-telopeptide and serum alkaline phosphatase at baseline and 6 months
  
• Frequency and severity of toxicity as measured by NCI CTC version 2.0
  
• Menopausal symptoms as measured by the Greene Climacteric Scale (GCS) at baseline, monthly during chemotherapy, at 6 months, 1 year, and 2 years after study entry
  
• Association of baseline serum estradiol levels with permanent cessation of menses
  
• Relationship between the subscales of the GCS (psychological, vasomotor, somatic and sexual) with type of chemotherapy, duration of chemotherapy, and menstrual cycle changes
  

OBJECTIVES:

• Compare the effectiveness of risedronate vs placebo in the prevention of bone loss in premenopausal women undergoing adjuvant or neoadjuvant chemotherapy for primary breast cancer.
• Compare the degree of bone loss over 1 year in these women according to menopausal status after 1 year of therapy.
• Determine the relationship of current climacteric symptoms, menstrual and reproductive history, and chemotherapy regimen with ovarian failure (permanent cessation of menses) in these women.
• Determine the relationship of baseline serum estradiol levels with ovarian failure in these women.

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.

• Arm I: Patients receive oral calcium and oral cholecalciferol daily and oral risedronate once weekly.
• Arm II: Patients receive calcium and cholecalciferol as in arm I and oral placebo once weekly.

In both arms, treatment begins during the first month of chemotherapy and continues for 1 year in the absence of unacceptable toxicity.

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.

PROJECTED ACCRUAL: A total of 220 patients (110 per treatment arm) will be accrued for this study within 11 months.