Treatment Regimen for Hormone-Positive HER2-Positive Breast Cancer
The recommended first-line treatment for hormone-positive HER2-positive breast cancer is the combination of trastuzumab, pertuzumab, and a taxane, which should be continued until disease progression or unacceptable toxicity. 1
First-Line Treatment
- The combination of trastuzumab, pertuzumab, and a taxane is the standard first-line treatment for HER2-positive breast cancer, including hormone-positive disease, unless there are contraindications to taxanes 2, 1
- Chemotherapy should continue for approximately 4-6 months or until maximal response, while HER2-targeted therapy should be continued until disease progression 2, 1
- For patients who completed trastuzumab-based adjuvant treatment more than 12 months before recurrence, first-line HER2-targeted therapy recommendations should be followed 2
- 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 2
Second-Line Treatment
- If disease progresses during or after first-line HER2-targeted therapy, trastuzumab emtansine (T-DM1) is recommended as second-line treatment 2, 1
- Trastuzumab deruxtecan (T-DXd) may be considered as an alternative second-line option based on more recent evidence 1
Third-Line and Beyond Treatment
- For progression after second-line therapy, if the patient has not received T-DM1, it should be offered 2
- If the patient has not received pertuzumab, it may be considered, though evidence for this approach is limited 2
- 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) 2
- When using lapatinib plus capecitabine, the recommended dosage of lapatinib is 1,250 mg (5 tablets) given orally once daily on Days 1-21 continuously in combination with capecitabine 2,000 mg/m²/day (in 2 divided doses) on Days 1-14 in a repeating 21-day cycle 3
Special Considerations for Hormone Receptor-Positive and HER2-Positive Disease
For patients with both hormone receptor-positive and HER2-positive disease, the following approaches may be considered:
- HER2-targeted therapy plus chemotherapy (strongest evidence and preferred approach) 2, 1
- Endocrine therapy plus trastuzumab or lapatinib (in selected cases) 2, 1
- Endocrine therapy alone (only in highly selected cases with low disease burden, significant comorbidities, or long disease-free interval) 2, 1
When using lapatinib with endocrine therapy, the recommended dose is 1,500 mg (6 tablets) given orally once daily continuously in combination with letrozole 2.5 mg once daily 3
When starting with HER2-targeted therapy plus chemotherapy, endocrine therapy may be added when chemotherapy ends while continuing HER2-targeted therapy 2, 1
Important Considerations
- Although endocrine therapy with or without HER2-targeted therapy is an option for hormone-positive HER2-positive disease, the majority of patients will still receive chemotherapy plus HER2-targeted therapy due to superior efficacy 2, 4
- The addition of HER2-targeted therapy to first-line aromatase inhibitors should be offered to patients with HR-positive, HER2-positive metastatic breast cancer in whom chemotherapy is not immediately indicated 2
- Recent evidence suggests that dual HER2-targeted therapy plus endocrine therapy may have better efficacy than chemotherapy-containing regimens with similar safety profiles 4
Common Pitfalls and Caveats
- Failure to re-biopsy accessible metastatic lesions to confirm HER2 status, as receptor status can change during disease progression 1, 5
- Discontinuing HER2-targeted therapy prematurely after chemotherapy completion instead of continuing until disease progression 2, 1
- Using trastuzumab in combination with anthracyclines outside of clinical trials due to high risk of cardiac toxicity 5
- Undertreatment of ER-/HER2+ breast cancer, which may require more aggressive treatment than ER+/HER2+ disease due to worse prognosis 6