Can monotherapy with trastuzumab (Herceptin) + endocrine therapy be used in ER (Estrogen Receptor) + HER2 (Human Epidermal growth factor Receptor 2) + early breast cancer patients with co-morbidities and elderly?

Treatment of ER+/HER2+ Early Breast Cancer in Elderly Patients with Comorbidities

For elderly patients with ER+/HER2+ early breast cancer who have comorbidities, monotherapy with trastuzumab plus endocrine therapy is an appropriate treatment option that balances efficacy with reduced toxicity.

Treatment Algorithm for Elderly Patients with ER+/HER2+ Early Breast Cancer

• Treatment decisions should be based on biological age rather than chronological age, with geriatric assessment recommended before finalizing treatment plans 1
• For elderly patients with ER+/HER2+ early breast cancer with comorbidities, consider:
  • Endocrine therapy combined with trastuzumab as an effective option with lower toxicity compared to chemotherapy-containing regimens 2
  • This approach is particularly suitable for patients with declining performance status or those unsuitable for chemotherapy 2

Evidence Supporting Trastuzumab + Endocrine Therapy

• Based on the PERTAIN study, endocrine therapy combined with trastuzumab (with or without pertuzumab) is a valid treatment option for HR+/HER2+ disease 2
• Clinicians may consider starting with endocrine therapy combined with trastuzumab upfront in patients whose performance status declines or who are unsuitable for chemotherapy 2
• The combination of anti-HER2 agents with endocrine therapy allows for prolongation of progression-free survival in patients with ER+/HER2+ tumors 2
• This approach is particularly valuable for patients not considered for cytotoxic chemotherapy due to age or comorbidities 2

Special Considerations for Elderly Patients

• Optimal treatment strategies should balance disease control and toxicity, with better tolerated therapies preferred in more frail patients 2
• In the first-line setting, endocrine therapy combined with trastuzumab is preferred for patients with HR+/HER2+ disease who are elderly or have comorbidities 2
• Treatment should be tailored according to Eastern Cooperative Oncology Group performance status, comorbidities, and personal preference 2
• Tools such as the G-8 score and Clinical Frailty Score can help assess frailty level to inform treatment decisions 2

Specific Recommendations for Early Breast Cancer

• For pT1, pN0 tumors (particularly those ≤0.5 cm), consider adjuvant endocrine therapy with trastuzumab without chemotherapy 2
• For patients with HR+/HER2+ early breast cancer with a perceived high risk of recurrence, consider extended adjuvant therapy 2
• In elderly patients with limited life expectancy, the goal shifts toward maintaining quality of life while providing disease control 1

Monitoring and Management of Potential Toxicities

• Cardiac monitoring is essential when administering trastuzumab to elderly patients due to potential cardiac adverse events 3
• For frail patients or those with comorbidities, consider initiating treatments at lower doses than in patients with better performance status 2
• Consider preplanned treatment holidays to improve tolerability in frail patients 2
• Monitor bone health closely, as aromatase inhibitors can accelerate bone loss; consider bone-modifying agents in patients at high risk for fractures 1

When to Consider More Aggressive Therapy

• For fit elderly patients with high-risk features, more aggressive therapy approaches may be warranted 1
• In patients with excellent performance status and minimal comorbidities, standard therapy with anti-HER2 agents plus chemotherapy followed by endocrine therapy may be appropriate 1
• The decision to use monotherapy versus combination therapy should be made on a case-by-case basis, considering the individual's risk profile and comorbidities 2