Study of Denosumab as Adjuvant Treatment for Women With High Risk Early Breast Cancer Receiving Neoadjuvant or Adjuvant Therapy (D-CARE)

Inclusion Criteria

• •Histologically confirmed, American Joint Committee on Cancer (AJCC) stage II or III breast cancer
• •High risk of breast cancer recurrence, defined as documented evidence of one or more of the following criteria:
• •i) Biopsy evidence of breast cancer in regional lymph node(s) (LN) (node-positive disease); Nodal micrometastases only are not considered node positive ii) Tumor size \> 5 cm (T3) or locally advanced disease (T4)
• •Documented pathological evaluation of the breast cancer for hormone receptor (estrogen receptor \[ER\] and progesterone receptor \[PR\]) status and HER-2 status
• •Subjects must be receiving or be scheduled to receive standard of care systemic adjuvant or neoadjuvant chemotherapy and/or endocrine therapy and/or HER-2 targeted therapy
• •For subjects receiving adjuvant therapy only:
• •subjects must have undergone complete resection of the primary tumor with clean surgical margins, or subjects must have undergone resection of the primary tumor and be scheduled for further treatment of the primary tumor with curative intent. Definitive treatment must be planned to be completed within approximately 9 months of randomization
• •Time between definitive surgery and randomization must be ≤ 12 weeks. Definitive surgery may include secondary interventions (e.g. to clear inadequate surgical margins)
• •Subjects with node positive disease must have undergone treatment of axillary LN with curative intent, or subjects must be scheduled for further treatment of regional lymph nodes with curative intent. Definitive treatment must be planned to be completed within approximately 9 months of randomization
• •Subjects must not have received prior neoadjuvant treatment. Endocrine treatment for less than 30 days prior to surgery is not considered prior neoadjuvant treatment
• •For subjects receiving neoadjuvant therapy only:
• •Time between start of neoadjuvant treatment and randomization must be ≤ 8 weeks and subjects must be scheduled to undergo definitive treatment (including surgery and/or radiotherapy) with curative intent within approximately 9 months of starting neoadjuvant treatment
• •Female subjects with age ≥ 18 years
• •Subjects with reproductive potential must have a negative pregnancy test within 14 days before randomization
• •Serum calcium or albumin-adjusted serum calcium ≥ 2.0 mmol/L (8.0 mg/dL) and ≤ 2.9 mmol/L (11.5 mg/dL)
• •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• •Written informed consent before any study-specific procedure is performed