Treatment of Bone Metastases in Locally Advanced HER2-Positive Breast Cancer
For patients with HER2-positive breast cancer with bone metastases, the recommended treatment is trastuzumab, pertuzumab, and a taxane as first-line therapy, along with bisphosphonates to reduce skeletal-related events. 1
Systemic Therapy for HER2-Positive Disease with Bone Metastases
First-line Treatment
- Trastuzumab + pertuzumab + taxane is the preferred first-line regimen 1
- This combination has demonstrated significant improvement in progression-free survival (18.5 vs 12.4 months) and overall survival (56.5 vs 40.8 months) compared to trastuzumab + taxane alone 2
- Cardiac monitoring should be performed before and during trastuzumab therapy
- Non-anthracycline-containing chemotherapy should be used with trastuzumab to avoid cardiotoxicity
Second-line Treatment
- T-DM1 (trastuzumab emtansine) is recommended after progression on first-line therapy 1
- High-quality evidence supports this recommendation with strong strength
Third-line and Beyond
- Tucatinib + capecitabine + trastuzumab may be offered, especially for patients with brain metastases 1
- Other HER2-targeted therapy combinations or T-DM1 (if not previously administered) 1
- Lapatinib + capecitabine has shown significant increase in time to progression in patients progressing after trastuzumab 1
Bone-Specific Management
Bisphosphonates/Bone-Modifying Agents
- Bisphosphonates are strongly recommended for all patients with bone metastases 1
Local Therapy for Bone Metastases
- Radiation therapy is an integral part of palliative treatment for bone metastases 1
- Surgery may be considered for limited metastatic presentations or risk of fracture 1
- For painful bone metastases, options include:
- External beam irradiation
- Stereotactic radiosurgery for limited metastases
- Radioactive bone-seeking isotopes 1
Treatment Duration and Monitoring
- HER2-targeted therapy should continue until disease progression or unacceptable toxicity 1
- Chemotherapy should be administered for at least 4-6 months or until maximum response, depending on toxicity and in the absence of progression 1
- Response evaluation should be performed after 2-3 cycles of chemotherapy by:
- Clinical evaluation
- Subjective symptom evaluation
- Blood tests
- Repeating initially abnormal radiologic examinations 1
Special Considerations
Hormone Receptor-Positive and HER2-Positive Disease
- For selected patients with ER/PR-positive and HER2-positive disease:
- Consider endocrine therapy plus HER2-targeted therapy as an alternative to chemotherapy 1
- This approach may be particularly suitable for patients with less aggressive disease
Brain Metastases
- HER2-positive breast cancer has high incidence of brain metastases
- For patients with brain metastases:
- Tucatinib + capecitabine + trastuzumab has shown efficacy in patients with brain metastases 1
- Local therapy (surgery or radiation) should be considered based on symptoms and extent of disease
Common Pitfalls to Avoid
- Avoiding bisphosphonates/bone-modifying agents: These are essential for all patients with bone metastases to reduce skeletal-related events
- Continuing anthracyclines with trastuzumab: This combination increases risk of cardiac dysfunction (27% incidence) 4
- Discontinuing HER2-targeted therapy after progression: Continuing HER2-blockade with a different regimen is beneficial even after progression on initial HER2-targeted therapy 1
- Underestimating the impact of bone metastases: Bone is the most common site of metastasis in breast cancer and significantly affects both quality of life and survival 5
- Inadequate pain management: Bone metastases often cause significant pain requiring multimodal approaches
By following this algorithmic approach to treatment, patients with HER2-positive breast cancer with bone metastases can achieve optimal outcomes in terms of disease control, symptom management, and quality of life.