What is the treatment approach for a patient with stage 4 breast cancer and bone metastasis?

Treatment for Stage 4 Breast Cancer with Bone Metastasis

Initiate bone-modifying agents (denosumab 120 mg subcutaneously every 4 weeks or zoledronic acid 4 mg IV every 3-4 weeks) immediately at diagnosis regardless of symptoms, combine with systemic therapy tailored to hormone receptor (HR) and HER2 status, and use radiation therapy for symptomatic lesions or fracture risk. 1, 2

Immediate Bone-Directed Therapy

All patients with bone metastases require bone-modifying agents at diagnosis, even without symptoms. 1, 2

• Denosumab 120 mg subcutaneously every 4 weeks is superior to zoledronic acid in delaying skeletal-related events (SREs) including pathological fractures, spinal cord compression, and need for bone radiation or surgery. 1, 2

• Zoledronic acid 4 mg IV can be administered every 12 weeks (rather than every 4 weeks) in patients with stable disease after 3-6 monthly treatments without compromising efficacy. 1

• Before starting any bone-modifying agent, obtain a complete dental evaluation and complete any necessary dental work to minimize osteonecrosis of the jaw (ONJ) risk. 1, 2

• Prescribe calcium and vitamin D supplements concurrently. 1

• The optimal duration of bone-modifying agent therapy is undefined, but it is reasonable to interrupt therapy after 2 years for patients in complete remission. 1

Systemic Therapy Selection by Tumor Subtype

Treatment stratification is based on HR and HER2 status, with endocrine therapy preferred over chemotherapy for HR-positive disease unless visceral crisis is present. 1, 2

HR-Positive/HER2-Negative Disease

• Endocrine therapy is first-line unless clinically aggressive disease with visceral crisis demands immediate cytoreduction. 1, 2

• Sequential single-agent endocrine therapies provide equivalent survival to combination regimens with superior tolerability. 1, 2

• The goal is palliation with minimal toxicity; treatments associated with minimal toxicity are preferred. 1

HER2-Positive Disease

• Trastuzumab-based therapy is indicated for all HER2-positive metastatic breast cancer. 3

• Continue HER2-targeted therapy even after progression, as sequential HER2-targeted therapies remain beneficial. 4

• Trastuzumab is administered at an initial dose of 4 mg/kg IV over 90 minutes, followed by 2 mg/kg weekly, or 8 mg/kg loading dose followed by 6 mg/kg every 3 weeks. 3

Triple-Negative Disease

• Chemotherapy is the primary systemic treatment option. 1

• Consider PARP inhibitors for patients with germline BRCA1/BRCA2 mutations. 1

Radiation Therapy for Bone Lesions

Single-fraction 8 Gy radiation is as effective as multi-fraction schemes for uncomplicated bone metastases. 1, 2

• Indications for radiation include moderate-to-severe pain, moderate-to-high fracture risk, or impending neurological complications. 1, 2

• Radiation therapy should be delivered after surgery for stabilization or separation surgery for metastatic spinal cord compression (MSCC). 1

• For limited metastatic presentations, radiation therapy is an integral part of palliative treatment. 1

Orthopedic Surgical Evaluation

Obtain orthopedic consultation for significant lesions in weight-bearing long bones or vertebrae, and for any patient with metastatic spinal cord compression. 1, 2

• Prophylactic surgical stabilization prevents pathological fractures in high-risk lesions. 1, 2

• Surgery may be considered for patients with bone-only metastasis, HR-positive tumors, HER2-negative tumors, patients <55 years, and those with good response to initial systemic therapy. 1

Oligometastatic Disease Considerations

For patients with bone-only metastasis or limited metastatic sites (≤5 lesions), multimodality treatment combining local ablative therapy with systemic therapy may be offered after multidisciplinary discussion. 1, 2

• Document tumor response to systemic therapy before pursuing local ablative approaches. 1, 2

• Local ablative therapy to all metastatic lesions may be offered on an individual basis; however, it is unknown if this leads to improved overall survival. 1

• Surgery of the primary tumor may be considered for patients with bone-only metastasis, particularly those with HR-positive/HER2-negative tumors, patients <55 years, and those with solitary bone metastases (HR 0.47 for survival benefit). 1

Treatment Goals and Patient Communication

The primary goal is palliation—maintaining and improving quality of life while potentially prolonging survival; stage IV breast cancer is not curative. 1, 2

• Discuss realistic treatment goals with patient and family from the outset. 1, 2

• Encourage active patient participation in treatment decisions, taking patient preferences into account regarding treatment options and methods of administration (intravenous or oral). 1, 2

• Specialist breast nurses should be available to all patients to provide crucial support. 1

Critical Pitfalls to Avoid

Do not withhold bone-modifying agents until symptoms develop—initiate at diagnosis of bone metastases. 1, 2

Do not use chemotherapy as first-line for HR-positive bone-predominant disease unless visceral crisis is present. 1, 2

Do not skip dental evaluation before bone-modifying agent initiation—osteonecrosis of the jaw is preventable. 1, 2

• Avoid invasive dental procedures during treatment with bone-modifying agents due to ONJ risk. 1, 4

• Do not perform surgery solely for local control without considering systemic disease burden and patient prognosis—surgery in stage IV disease is palliative only and should not delay systemic therapy. 4

• Do not broadly consider local therapy with surgery and/or radiation without patient engagement in the decision; this may be reasonable only in select patients responding to initial systemic therapy. 1