What is the primary approach for treating recurrence of Invasive Ductal Carcinoma (IDC) in HER2 (Human Epidermal growth factor Receptor 2)-positive patients?

Treatment of Recurrent HER2-Positive Invasive Ductal Carcinoma

For patients with recurrent HER2-positive invasive ductal carcinoma, the primary approach should be HER2-targeted therapy in combination with chemotherapy, with the specific regimen determined by the timing of recurrence relative to prior adjuvant treatment. 1

Treatment Algorithm Based on Timing of Recurrence

If Recurrence Occurs >12 Months After Completing Trastuzumab-Based Adjuvant Treatment:

• First-line treatment: Trastuzumab + pertuzumab + taxane (docetaxel or paclitaxel) 1
  • This combination has demonstrated high-quality evidence for improved progression-free and overall survival
  • Continue HER2-targeted therapy after completion of chemotherapy until disease progression

If Recurrence Occurs ≤12 Months After Completing Trastuzumab-Based Adjuvant Treatment:

• Second-line treatment: Trastuzumab deruxtecan (T-DXd) 1
  • T-DXd has shown superior efficacy compared to T-DM1 in the second-line setting
  • If T-DXd is not available, T-DM1 remains an appropriate alternative 1

Subsequent Lines of Therapy

Third-Line and Beyond:

If disease progresses after second-line therapy and the patient has already received pertuzumab and T-DM1/T-DXd, options include:

• Lapatinib plus capecitabine
• Trastuzumab plus chemotherapy
• Lapatinib plus trastuzumab
• Trastuzumab plus endocrine therapy (if hormone receptor-positive) 1

Special Considerations for Hormone Receptor-Positive/HER2-Positive Disease

For patients with both hormone receptor-positive and HER2-positive disease:

1. Primary approach: HER2-targeted therapy plus chemotherapy 1
2. Alternative approaches (for selected cases):
   • Endocrine therapy plus trastuzumab or lapatinib
   • Endocrine therapy alone (only in special circumstances with low disease burden, significant comorbidities, or long disease-free interval) 1
3. Sequential approach: Consider adding endocrine therapy to HER2-targeted therapy after completion of chemotherapy 1

Duration of Treatment

• Continue HER2-targeted therapy until disease progression or unacceptable toxicity 1
• Chemotherapy should be administered for approximately 4-6 months or until maximal response, after which HER2-targeted therapy should be continued alone 1

Monitoring and Toxicity Management

• Regular cardiac assessment is essential during HER2-targeted therapy due to potential cardiotoxicity 1
• Monitor for infusion-related reactions, especially during first infusion of pertuzumab 2
• For T-DXd, monitor for interstitial lung disease/pneumonitis which can be severe or fatal

Pitfalls and Caveats

1. Do not discontinue HER2-targeted therapy at disease progression - Continuing HER2 suppression with a different HER2-targeted agent is beneficial 1

2. Avoid undertreatment of HER2-positive disease - HER2-targeted therapy should be the backbone of treatment for virtually all patients with HER2-positive metastatic breast cancer 1

3. Consider cardiac risk - Patients with significant cardiac dysfunction may require alternative approaches or careful monitoring if HER2-targeted therapy is used 1

4. Don't miss the opportunity for dual HER2 blockade - The combination of trastuzumab and pertuzumab provides superior outcomes compared to single-agent HER2 blockade in the first-line setting 1

5. Recognize the importance of timing since adjuvant therapy - Treatment selection should be based on the interval since completion of adjuvant therapy, with different approaches for early (<12 months) versus late (>12 months) recurrences 1