Patient case: 56-year-old female with breast cancer; genetic feature: ERBB2

Clinical trial: Chemotherapy and/or Hormone Therapy With or Without Zoledronate in Treating Women With Stage II or Stage III Breast Cancer

Summary: RATIONALE: Zoledronate may delay or prevent the formation of bone metastases. It is not yet known whether chemotherapy and/or hormone therapy are more effective with or without zoledronate in preventing cancer recurrence and bone metastases in women with breast cancer.
  PURPOSE: This randomized phase III trial is studying giving chemotherapy and/or hormone therapy together with zoledronate to see how well they work compared to chemotherapy and/or hormone therapy alone in preventing cancer recurrence and bone metastases in women with stage II or stage III breast cancer.

Detailed description: OBJECTIVES:
  Primary
  -  Compare disease-free survival of women with stage II or III breast cancer at high risk of relapse treated with neoadjuvant or adjuvant chemotherapy and/or hormonal therapy with vs without zoledronate.
  Secondary
  -  Compare time to bone metastases, as first recurrence, in patients treated with these regimens.
  -  Compare time to bone metastases, per se, in patients treated with these regimens.
  -  Compare time to distant metastases in patients treated with these regimens.
  -  Compare overall survival in patients treated with these regimens.
  -  Compare the reduction in skeletal-related events (fractures, spinal cord compression, radiotherapy to the bone, surgery to the bone, and hypercalcemia) before and after the development of bone metastases in patients treated with these regimens.
  -  Determine the safety and toxicity of zoledronate in patients treated with these regimens.
  -  Correlate prognostic factors, such as estrogen-receptor and progesterone-receptor status, TNM stage, tumor grade, HER2/neu status, and menopausal status with treatment outcome in patients treated with these regimens.
  -  Determine more specific prognostic indicators for the development of bone metastases and factors that are able to predict specific benefit from bisphosphonate treatment using proteomics, tissue micro-array, and other modern techniques in these patients.
  OUTLINE: This is a randomized, open-label, parallel-group, multicenter study. Patients are stratified according to participating center. Patients are randomized to 1 of 2 treatment arms.
  -  Arm I: Patients receive neoadjuvant or adjuvant chemotherapy and/or hormonal therapy. Patients also receive concurrent zoledronate IV over 15 minutes every 3-4 weeks for 6 doses, every 3 months for 8 doses, and then every 6 months for 5 doses in the absence of disease progression or unacceptable toxicity.
  -  Arm II: Patients receive neoadjuvant or adjuvant chemotherapy and/or hormonal therapy alone.
  After completion of study treatment, patients are followed annually for 5 years.
  PROJECTED ACCRUAL: A total of 3,300 patients (1,650 per treatment arm) will be accrued for this study within 3 years.

Eligibility: DISEASE CHARACTERISTICS:
  -  Diagnosis of primary breast cancer, meeting 1 of the following staging criteria:
  -  Stage II
  -  Stage III
  -  T stage ≥ T1
  -  Receiving OR scheduled to receive chemotherapy and/or endocrine therapy
  -  For patients receiving neoadjuvant therapy
  -  Tumor > 5 cm (T3), features of locally advanced disease (T4), OR biopsy-proven lymph node involvement (N1)
  -  Scheduled to proceed to definitive surgery and/or radical radiotherapy with curative intent within 6 months of starting neoadjuvant therapy
  -  No more than 30 days between initiation of neoadjuvant therapy and start of study drug
  -  For patients receiving adjuvant therapy
  -  Must have undergone complete primary tumor resection and treatment of axillary lymph nodes*
  -  Must have lymph node involvement
  -  No prior neoadjuvant therapy**
  -  No more than 60 days since prior definitive surgery NOTE: *Patients whose treatment plan includes further primary tumor resection and/or treatment of the axillary lymph nodes (e.g., clearance or radiotherapy) with curative intent after completion of chemotherapy are eligible provided the treatment is completed within 9 months of study entry
  NOTE: **Preoperative endocrine therapy with a duration of < 30 days is not considered prior neoadjuvant therapy
  -  No evidence of recurrent or metastatic disease
  -  No history of breast cancer, except ductal carcinoma in situ or lobular carcinoma in situ
  -  Hormone receptor status:
  -  Not specified
  PATIENT CHARACTERISTICS:
  Age
  -  18 and over
  Sex
  -  Female
  Menopausal status
  -  Premenopausal or postmenopausal
  Performance status
  -  Karnofsky 80-100% OR
  -  ECOG 0-1
  Life expectancy
  -  Not specified
  Hematopoietic
  -  Not specified
  Hepatic
  -  Not specified
  Renal
  -  Creatinine ≤ 1.5 times upper limit of normal
  Other
  -  Not pregnant or nursing
  -  Fertile patients must use effective contraception
  -  No active dental problems, including dental abscess or infection of the jaw bone (e.g., maxilla or mandible)
  -  No prior or current diagnosis of osteonecrosis of the jaw
  -  No other malignancy within the past 5 years (including prior contralateral breast cancer) except nonmelanoma skin cancer or curatively treated carcinoma in situ of the cervix
  -  No history of disease with influence on bone metabolism, including any of the following:
  -  Paget's disease of the bone
  -  Primary hyperparathyroidism
  -  Osteoporosis requiring treatment or likely to require treatment within the next 6 months
  -  No other severe physical or psychological disease that would preclude study compliance
  -  No known hypersensitivity to bisphosphonates
  PRIOR CONCURRENT THERAPY:
  Chemotherapy
  -  See Disease Characteristics
  Endocrine therapy
  -  See Disease Characteristics
  Radiotherapy
  -  See Disease Characteristics
  Surgery
  -  See Disease Characteristics
  -  More than 4 weeks since prior and no concurrent dental or jaw surgery (e.g., extractions or implants)
  -  Dental fillings, teeth scaling and polishing, or minor gingival surgery within the past 4 weeks are allowed
  Other
  -  More than 1 year since prior bisphosphonates
  -  More than 30 days since prior investigational drugs
  -  No concurrent investigational drugs (i.e., not locally approved for any indication)

Relevance to patient case: definitely relevant