Denosumab in Treating Patients with Breast Cancer and Bone Metastases

Inclusion Criteria

• Patients have histological confirmation of breast carcinoma
• Patients have progressive metastatic disease with predominantly bone metastasis with 1 or more lesions and at least 1 bone lesion has pathological confirmation, have not been treated or have been treated with any prior therapies (including bisphosphonate treatment and/or radiation therapy); patients can have soft tissue involvement (lymph node and skin) and/or metastatic lesions at major organ sites (i.e. lung, liver, etc)
• Patients have positive estrogen receptor (ER) expression in the primary tumor site by immunohistochemistry (IHC) (defined as >= 10%) (progesterone receptor [PR] status is not required)
• Absolute neutrophil count (ANC) >= 1.0 x 10^9/L
• Platelet count >= 50 x 10^9/L
• Hemoglobin >= 9.0 g/dL
• Left ventricular ejection fraction (LVEF) >= 45% if patient has known cardiac dysfunction history
• Calculated creatinine clearance > 30 ml/min
• Aspartate aminotransferase (AST) =< 2.5 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) =< 2.5 x ULN
• Alkaline phosphatase (Alp) =< 2.5 x ULN
• Total bilirubin =< 2.0 x ULN
• Serum calcium or albumin-adjusted serum calcium >= 2.0 mmol/L (8.0 mg/dL) and =< 2.9 mmol/L (11.5 mg/dL)
• Patients have ability and willingness to sign written informed consent
• Female patients of childbearing potential (a female not free from menses > 2 years or not surgically sterilized) must be willing to use highly effective contraception to prevent pregnancy or agree to abstain from heterosexual activity throughout the study; highly effective contraception, defined as male condom with spermicide, diaphragm with spermicide, intra-uterine device; highly effective contraception must be used by both sexes during the study and must be continued for 5 months after the last dose of denosumab
• Female patients of childbearing potential must have negative serum pregnancy test =< 21 days prior to starting study treatment
• Patients have CTC >= 3

Exclusion Criteria

• Patients have known sensitivity to any of the products to be administered during the study (e.g., mammalian derived products, calcium, or vitamin D)
• Patients receiving concurrent anti-cancer therapy (chemotherapy, immunotherapy, radiation therapy and biological therapy) while taking study medication; however, patients receiving CDK4/6 inhibitor ormTOR inhibitor as a standard of care while on study is permitted
• Patients with metastatic sites that requires chemotherapy
• Patients with active infection and requiring intravenous (IV) or oral antibiotics
• Patients with concurrent disease or condition that would make them inappropriate for study participation, or any serious medical disorder that would interfere with patients’ safety
• Patients have HER2-positive breast carcinoma (IHC staining more than 3+ or HER2 gene amplification by fluorescent in situ hybridization [FISH])
• Patient is pregnant or breast feeding, or planning to become pregnant within 5 months after the end of treatment
• Patient is of child bearing potential and is not willing to use, in combination with her partner, two highly effective methods of contraception or abstinence during treatment and for 5 months after the end of treatment
• Patients have prior history or current evidence of osteonecrosis/osteomyelitis of the jaw
• Patients have active dental or jaw condition which requires oral surgery, including tooth extraction
• Patients have non healed dental/oral surgery, including tooth extraction
• Patients planned invasive dental procedures
• Patients experiencing a visceral crisis including severe organ dysfunction as assessed by > grade (Gr) 2 symptomatic toxicities, laboratory studies, and/or rapid progression of disease originating from visceral metastasis
• Patients that have received the study medication (Xgeva/Prolia)