What is the recommended treatment approach for a patient with HER2 (Human Epidermal growth factor Receptor 2) positive breast cancer?

Treatment Approach for HER2-Positive Breast Cancer

For patients with HER2-positive breast cancer, the recommended first-line treatment is a combination of trastuzumab, pertuzumab, and a taxane, which has demonstrated significant improvement in survival outcomes. 1

First-Line Treatment

• The combination of trastuzumab, pertuzumab, and a taxane is the standard first-line treatment for HER2-positive advanced breast cancer, unless there are contraindications to taxanes 1
• Chemotherapy should continue for approximately 4-6 months or until maximal response, while HER2-targeted therapy should be continued until disease progression or unacceptable toxicity 1
• For patients who completed trastuzumab-based adjuvant treatment more than 12 months before recurrence, first-line HER2-targeted therapy recommendations should be followed 1
• For patients who completed trastuzumab-based adjuvant treatment less than or equal to 12 months before recurrence, second-line HER2-targeted therapy recommendations should be followed 1

Second-Line Treatment

• If disease progresses during or after first-line HER2-targeted therapy, trastuzumab deruxtecan (T-DXd) is recommended as second-line treatment based on the most recent evidence 1
• If T-DXd is not available, trastuzumab emtansine (T-DM1) should be offered as second-line treatment 1

Third-Line and Beyond Treatment

• For progression after second-line therapy, if the patient has not received T-DM1, it should be offered 1
• If the patient has not received pertuzumab, it may be considered, though evidence for this approach is limited 1
• For patients who have already received both pertuzumab and T-DM1, third-line options include lapatinib plus capecitabine, other chemotherapy combinations with trastuzumab, lapatinib plus trastuzumab, or hormonal therapy (in hormone receptor-positive disease) 1
• Tucatinib-based regimens should be considered particularly for patients with brain metastases 2

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

• For patients with both hormone receptor-positive and HER2-positive disease, clinicians may recommend one of the following approaches:
  • HER2-targeted therapy plus chemotherapy (strongest evidence) 1
  • Endocrine therapy plus trastuzumab or lapatinib (in selected cases) 1
  • Endocrine therapy alone (only in selected cases with low disease burden, significant comorbidities, or long disease-free interval) 1
• When starting with HER2-targeted therapy plus chemotherapy, endocrine therapy may be added when chemotherapy ends or when cancer progresses 1

Treatment Duration and Monitoring

• After completing chemotherapy in combination regimens, HER2-targeted therapy should be continued until disease progression or unacceptable toxicity 1
• Regular cardiac monitoring is essential due to the potential for left ventricular dysfunction with HER2-targeted therapies 3, 4
• Infusion-related reactions and hypersensitivity should be monitored, particularly during initial infusions 3

Emerging Therapies

• Newer anti-HER2 agents showing promise in later-line settings include margetuximab and neratinib 5, 2
• Novel antibody-drug conjugates are demonstrating efficacy in heavily pretreated patients 6, 7

Common Pitfalls and Caveats

• Failure to re-biopsy accessible metastatic lesions to confirm HER2 status, as receptor status can change during disease progression 8
• Discontinuing HER2-targeted therapy prematurely after chemotherapy completion instead of continuing until disease progression 1
• Overlooking the potential for cardiac toxicity with HER2-targeted therapies, particularly in patients with pre-existing cardiac conditions 3
• Not considering brain metastases, which are common in HER2-positive disease and may require specialized treatment approaches 2