What is the optimal management for an 85‑year‑old woman with ER (estrogen receptor)‑positive, PR (progesterone receptor)‑positive, HER2 (human epidermal growth factor receptor 2)‑positive breast adenocarcinoma presenting with an isolated sternal mass?

Management of 85-Year-Old with Triple-Positive Breast Adenocarcinoma Presenting as Isolated Sternal Mass

For an 85-year-old woman with ER+/PR+/HER2+ breast cancer presenting with an isolated sternal mass, initiate systemic therapy with endocrine therapy plus HER2-targeted therapy (trastuzumab plus pertuzumab), reserving chemotherapy only if rapid disease control is needed, followed by consideration of local ablative treatment to the sternal lesion if she achieves good systemic response. 1, 2, 3

Initial Diagnostic Workup

Before initiating treatment, complete staging is mandatory to confirm this is truly isolated disease 1:

• Full staging workup including complete history, physical examination, laboratory tests (complete blood count, liver and renal function, alkaline phosphatase, calcium), and imaging of chest and abdomen (preferably CT) and bone scan 1
• Brain MRI to exclude asymptomatic CNS metastases, particularly important in HER2+ disease 1
• PET-CT is valuable here to confirm the sternal mass is the only site of disease and exclude other occult metastases 1
• Biopsy of the sternal mass to confirm metastatic disease and reassess ER/PR/HER2 status, as receptor status can change from primary to metastatic sites 1
• Cardiac assessment (echocardiogram or MUGA scan) to establish baseline left ventricular ejection fraction before HER2-targeted therapy 3

Systemic Treatment Strategy

Primary Recommendation: Endocrine Therapy Plus Dual HER2 Blockade

The optimal first-line approach for this 85-year-old patient is endocrine therapy combined with trastuzumab plus pertuzumab, avoiding chemotherapy initially. 1

Here's the rationale:

• Age and performance status should not be the sole reason to withhold effective therapy, but should guide treatment intensity 1
• For HR+/HER2+ disease, the choice between chemotherapy versus endocrine therapy depends on tumor grade, biomarker expression, performance status, comorbidities, and need for rapid disease control 1
• An isolated sternal metastasis without visceral crisis does not require immediate chemotherapy 1
• Dual HER2 blockade (trastuzumab plus pertuzumab) combined with an aromatase inhibitor has demonstrated efficacy in HR+/HER2+ metastatic disease with median PFS of 11.0 months versus 5.6 months with single HER2 blockade 4

Specific Regimen

• Trastuzumab: Loading dose 8 mg/kg IV, then maintenance 6 mg/kg IV every 3 weeks 4
• Pertuzumab: Standard dosing per protocol 2, 3
• Aromatase inhibitor: Letrozole 2.5 mg daily, anastrozole 1 mg daily, or exemestane 25 mg daily 4
• Continue HER2-targeted therapy indefinitely until disease progression or unacceptable toxicity 2, 3

When to Add Chemotherapy

Consider adding a taxane to the HER2-targeted therapy if 1, 2, 3:

• Rapid clinical progression occurs on endocrine therapy plus HER2 blockade
• Life-threatening visceral metastases develop
• Need for rapid symptom or disease control emerges
• If chemotherapy is added, continue for approximately 4-6 months or until maximal response, while maintaining HER2-targeted therapy 2, 3

Local Treatment Considerations

Oligometastatic Approach

This patient with an isolated sternal metastasis is a candidate for aggressive local therapy after achieving systemic disease control. 1

• A multimodal approach including locoregional treatments with curative intent should be considered for patients with oligometastatic disease that is highly sensitive to systemic therapy 1
• Patients with single-site metastatic disease can achieve long-term survival with combined systemic and local ablative treatment 1
• Local treatment options include surgical resection or radiotherapy to the sternal lesion, performed after demonstrating response to systemic therapy 1
• This approach is supported by data showing favorable survival in selected patients undergoing radical local therapy for limited metastatic disease, though based on retrospective series 1

Timing of Local Therapy

• Initiate systemic therapy first 1
• Reassess with imaging after 2-4 months of systemic therapy 1
• If excellent response achieved, consider definitive local treatment (surgery or radiotherapy) to the sternal lesion 1

Monitoring and Supportive Care

Treatment Monitoring

• Evaluate response every 2-4 months with imaging of target lesions 1
• Monitor cardiac function regularly during trastuzumab therapy; discontinue if clinically significant decrease in LVEF occurs 3
• Tumor markers (CA 15-3, CA 27.29) may assist in evaluating response, particularly if the sternal lesion becomes non-measurable after treatment 1

Supportive Care Priorities

• Early introduction of expert palliative care for effective control of pain and bone-related symptoms from the sternal metastasis 1
• Supportive care allowing safer and more tolerable delivery of appropriate treatments should always be part of the treatment plan 1
• Bone-directed therapy (bisphosphonates or denosumab) should be considered for skeletal metastasis 1

Critical Prognostic Considerations

Favorable Features in This Case

• ER+/PR+/HER2+ subtype has better survival than ER-/PR-/HER2+ disease, with 8-year survival rates reaching 37% with optimal dual HER2 blockade 5, 6
• Isolated bone metastasis (sternal) has more favorable prognosis than visceral or multiple metastatic sites 6
• HR-positive status is a favorable prognostic feature in HER2+ metastatic disease 5

Expected Outcomes

• Median overall survival of approximately 57 months can be expected with optimal first-line trastuzumab, pertuzumab, and endocrine therapy 5
• Approximately 26% of patients become long-term responders with modern HER2-targeted therapy 5
• The ER+/PR+/HER2+ group shows significantly better disease-free survival and breast cancer-specific survival than ER+/PR-/HER2+ patients 7

Common Pitfalls to Avoid

• Do not delay HER2-targeted therapy: Postponing trastuzumab may eliminate the survival advantages demonstrated in pivotal trials 5
• Do not discontinue HER2-targeted therapy when stopping chemotherapy: This compromises outcomes; HER2 blockade must continue until progression 3
• Do not use lapatinib as first-line therapy: Lapatinib-based regimens are less effective than trastuzumab-based regimens in HER2+ metastatic disease 4
• Do not perform "palliative" surgery to the sternal lesion initially: Systemic therapy should be the first treatment; local therapy is considered only after demonstrating systemic response 1
• Do not assume age alone precludes aggressive therapy: The 85-year-old age should not be the sole reason to withhold effective HER2-targeted therapy and endocrine therapy, which are generally well-tolerated 1