What is the treatment for vertebral metastasis in a patient with locally advanced breast cancer that is Human Epidermal growth factor Receptor 2 (HER2) positive?

Treatment of Vertebral Metastasis in HER2-Positive Locally Advanced Breast Cancer

The optimal treatment for vertebral metastasis in a patient with locally advanced HER2-positive breast cancer is mastectomy combined with vertebral radiotherapy (option A), which should be followed by appropriate systemic HER2-targeted therapy. 1

Local Treatment of Vertebral Metastases

Radiotherapy Approach

• For vertebral metastases in HER2-positive breast cancer, radiotherapy is the preferred local treatment option, as it can effectively control pain, prevent pathological fractures, and improve quality of life 1
• Stereotactic radiosurgery (SRS) should be considered for limited vertebral metastases, while whole-brain radiotherapy plus memantine with hippocampal avoidance (WB-M+HA) may be appropriate for more extensive disease 1
• After local treatment with radiotherapy, serial imaging every 2-4 months should be used to monitor for local recurrence or new metastatic disease 1

Surgical Considerations

• Mastectomy is indicated for the primary tumor in locally advanced breast cancer to achieve local control 1
• Surgical intervention for vertebral metastases should be considered only for cases with significant spinal cord compression, spinal instability, or when a large lesion (>3-4 cm) causes symptomatic mass effect 1
• When surgery is performed for vertebral metastases, postoperative radiotherapy should be recommended to reduce the risk of local recurrence 1

Systemic Therapy Options

First-line Systemic Therapy

• Following local treatment, patients should receive systemic HER2-targeted therapy according to established algorithms for HER2-positive metastatic breast cancer 1
• The standard first-line systemic therapy is a taxane combined with trastuzumab and pertuzumab 2, 3
• For patients with stable vertebral metastases after local therapy, systemic therapy should not be switched if the extracranial disease is not progressive 1

Second-line and Beyond

• For patients with progressive disease after first-line therapy, trastuzumab deruxtecan is the preferred second-line option 3
• The tucatinib, capecitabine, and trastuzumab regimen (HER2CLIMB) should be strongly considered, particularly for patients with CNS involvement including vertebral metastases 1
• This regimen has demonstrated significant improvement in CNS progression-free survival (HR: 0.32; 95% CI, 0.22-0.48) and intracranial overall survival (HR: 0.58; 95% CI, 0.4-0.85) 1

Special Considerations for HER2-Positive Disease with Vertebral Metastases

• HER2-positive breast cancer has a higher propensity for CNS metastases, including vertebral involvement, making aggressive local and systemic treatment particularly important 4
• For patients with asymptomatic vertebral metastases <2 cm without mass effect, systemic therapy with HER2-directed agents with known CNS activity may be considered before local therapy 1
• The combination of tucatinib, capecitabine, and trastuzumab may allow delay of local therapy until evidence of intracranial progression in selected patients 1
• Clinicians should have a low threshold for performing diagnostic MRI in patients with any neurologic symptoms suggestive of spinal involvement 1

Treatment Algorithm

1. Initial Assessment:

   • Evaluate extent of vertebral metastasis, presence of symptoms, and overall disease burden 1
   • Assess performance status and prognosis 1

2. Local Treatment:

   • For symptomatic vertebral metastases: Radiotherapy to the vertebral lesion(s) 1
   • For the primary tumor: Mastectomy 1

3. Systemic Therapy:

   • First-line: Taxane + trastuzumab + pertuzumab 2, 3
   • Second-line: Trastuzumab deruxtecan or tucatinib + capecitabine + trastuzumab (especially with CNS involvement) 1, 3
   • Third-line and beyond: Consider tucatinib-based combination, neratinib + capecitabine, or trastuzumab + chemotherapy 1, 3

4. Monitoring and Follow-up:

   • Serial imaging every 2-4 months to monitor response and detect progression 1
   • Low threshold for additional MRI with any new neurological symptoms 1

Common Pitfalls and Caveats

• Vertebral chemotherapy alone (option B) is not a standard approach and lacks evidence for efficacy in this setting 1
• Mastectomy + chemotherapy without local treatment of vertebral metastases (option C) is suboptimal as it fails to address the local control of vertebral disease, which is crucial for preventing neurological complications 1
• Delaying radiotherapy in favor of systemic therapy should only be considered for asymptomatic patients with small metastases and when using regimens with proven CNS activity, such as tucatinib-based therapy 1
• Treatment decisions should take into account the patient's performance status, extent of disease, and prior therapies 1