Treatment Approach for HER2-Positive Breast Cancer

First-Line Treatment

The American Society of Clinical Oncology recommends the combination of trastuzumab, pertuzumab, and a taxane as the standard first-line treatment for HER2-positive advanced breast cancer, unless there are contraindications to taxanes 4, 5
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 3, 6
For patients who completed trastuzumab-based adjuvant treatment more than 12 months before recurrence, first-line HER2-targeted therapy recommendations should be followed 4, 5
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 4, 7

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 8
If T-DXd is not available, trastuzumab emtansine (T-DM1) should be offered as second-line treatment 2, 4

For progression after second-line therapy, if the patient has not received T-DM1, it should be offered 4, 5
If the patient has not received pertuzumab, it may be considered, though evidence for this approach is limited 3, 6
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) 4, 7

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) 4, 9
- Endocrine therapy plus trastuzumab or lapatinib (in selected cases) 5, 6
- Endocrine therapy alone (only in selected cases with low disease burden, significant comorbidities, or long disease-free interval) 4, 5
When starting with HER2-targeted therapy plus chemotherapy, endocrine therapy may be added when chemotherapy ends or when cancer progresses 3, 7

After completing chemotherapy in combination regimens, HER2-targeted therapy should be continued until disease progression or unacceptable toxicity 4, 5

Failure to re-biopsy accessible metastatic lesions to confirm HER2 status, as receptor status can change during disease progression 10
Discontinuing HER2-targeted therapy prematurely after chemotherapy completion instead of continuing until disease progression 4, 5