What is the recommended approach for metastasis-directed therapy in oligometastatic (having a limited number of metastases) breast cancer?

Metastasis-Directed Therapy in Oligometastatic Breast Cancer

For oligometastatic breast cancer patients who maintain good response to systemic therapy for at least 3-6 months, metastasis-directed therapy (MDT) should be combined with continued systemic treatment using surgery, stereotactic radiotherapy, or ablative techniques to all metastatic sites, though patients must understand that overall survival benefit remains unproven. 1

Patient Selection Criteria

Before considering MDT, confirm the following:

• ≤5 metastatic lesions detected on complete imaging staging, preferably with PET scan 1, 2
• Biopsy confirmation of metastatic disease when feasible 1, 2
• Complete imaging history available to assess disease dynamics and identify induced/recurrent oligometastatic disease 1, 2
• Documented tumor response to systemic therapy for 3-6 months minimum before MDT 1
• Mandatory multidisciplinary tumor board discussion before any treatment decisions 1, 2

Treatment Algorithm

Step 1: Systemic Therapy Foundation

Continue or optimize systemic therapy based on tumor biology:

• HR+/HER2- disease: Endocrine therapy with CDK4/6 inhibitors 2
• HER2+ disease: Anti-HER2 targeted therapy 2
• Triple-negative disease: Chemotherapy ± immunotherapy if PD-L1 positive 2
• BRCA-mutated disease: Consider PARP inhibitors 1, 2

Step 2: Local Therapy Options

Select MDT modality based on metastatic site and resectability:

• Surgery with or without adjuvant radiotherapy: For isolated, completely resectable lesions, particularly in breast/axilla, lung, or liver 1, 2
• Stereotactic body radiotherapy (SBRT): High-dose ablative radiation for non-resectable or multiple oligometastatic lesions 1, 2, 3
• Image-guided ablation: Radiofrequency, microwave, or cryotherapy for targeted lesion destruction 1
• Selective internal radiotherapy: Specifically for liver metastases 1, 2

Step 3: Timing Strategy

Document tumor response with systemic treatment before suggesting local ablative therapy 1, 2. Recent data shows patients experiencing oligoprogression after median 11.3 months on systemic therapy achieved median post-radiotherapy progression-free survival of 11.3 months when treated with SBRT while maintaining the same systemic treatment 3.

Favorable Prognostic Features

Patients most likely to benefit from aggressive MDT:

• HR+/HER2- disease with bone-only or non-visceral metastases 3, 4
• Age <55 years 1
• ≤2 oligometastatic lesions (90% of successful cases) 3
• Bone or lymph node involvement rather than visceral disease 3
• Durable pre-oligoprogression PFS (>11 months on systemic therapy) 3

Site-Specific Management

Bone Metastases

• Bone-modifying agents (zoledronate or denosumab) are mandatory for all patients with bone metastases regardless of symptoms 1, 2
• Zoledronate can be administered every 12 weeks after 3-6 monthly treatments in stable disease 1
• Denosumab requires continued 4-week dosing and is more effective than zoledronate in delaying skeletal-related events 1
• Orthopedic evaluation required for significant lesions in long bones or vertebrae 1
• Single 8-Gy radiotherapy fraction equals fractionated schemes for uncomplicated bone metastases 1

Primary Tumor Management

Do NOT perform locoregional treatment of the intact primary tumor in asymptomatic stage IV disease—this does not improve overall survival 1, 2. Surgery of the primary may only be considered for patients with bone-only metastasis, HR-positive tumors, HER2-negative tumors, age <55 years, or those with excellent response to systemic therapy 1.

CNS Oligoprogressive Disease

For patients with stable extracranial disease but CNS progression:

• Maintain current systemic therapy and add local therapy (stereotactic radiotherapy) to CNS lesions 1
• After second or third intracranial progression on trastuzumab-pertuzumab in HER2+ disease, switch to tucatinib/trastuzumab/capecitabine or trastuzumab deruxtecan (T-DXd) 1

Critical Evidence Limitations and Patient Counseling

Patients must be informed before treatment that overall survival benefit from local ablative therapy to all metastatic lesions remains unknown 1. The evidence supporting MDT comes primarily from:

• Retrospective series with selection bias 5, 6, 4
• Subgroup analyses from prospective trials 4
• The SABR-COMET trial (histology-agnostic, included breast cancer patients) showing promising results 6
• Recent prospective-retrospective data showing only 15% of patients experienced subsequent progression in SBRT-treated sites 3

The ongoing CHLOE study (HER2+ disease) and NRG BR002 trial will provide definitive randomized data on whether MDT improves outcomes in oligometastatic breast cancer 1, 4.

Common Pitfalls to Avoid

• Do not offer MDT to patients who have not demonstrated at least 3-6 months of response to systemic therapy—this selects against rapidly progressive biology 1
• Do not treat the primary tumor in asymptomatic stage IV disease expecting survival benefit—Level II evidence shows no OS improvement 1, 2
• Do not delay systemic therapy to pursue local treatment first—systemic control must be established before MDT 1, 2
• Do not forget bone-modifying agents—these are evidence-based for all bone metastases and reduce skeletal-related events 1, 2
• Do not proceed without multidisciplinary discussion—patient selection is critical and requires input from medical oncology, radiation oncology, and surgical oncology 1, 2