Treatment of ER-Negative, PR-Negative, HER2-Positive Breast Cancer

First-Line Treatment for Metastatic Disease

The American Society of Clinical Oncology recommends the combination of trastuzumab, pertuzumab, and a taxane for first-line treatment of metastatic ER-negative, PR-negative, HER2-positive breast cancer, unless the patient has a contraindication to taxanes, with high-quality evidence and strong recommendation strength 1, 2
Chemotherapy should continue for approximately 4-6 months or until maximal response, depending on toxicity and in the absence of progression, with trastuzumab and pertuzumab continuing until progression or unacceptable toxicities 2, 4

For locally advanced or high-risk early-stage disease, neoadjuvant chemotherapy with trastuzumab, pertuzumab, and a taxane for 3-6 cycles, followed by surgery, is recommended 3
Postmastectomy radiation therapy is mandatory for locally advanced presentations, and can be given concurrently with HER2-targeted therapy 3
Trastuzumab plus pertuzumab should be continued to complete one year of HER2-targeted therapy from the start of neoadjuvant treatment 3

The American Society of Clinical Oncology recommends trastuzumab emtansine (T-DM1) as second-line treatment for HER2-positive breast cancer that has progressed during or after first-line HER2-targeted therapy, based on high-quality evidence with strong recommendation strength 1, 2

For patients with disease progression during or after second-line or greater HER2-targeted therapy, third-line or greater HER2-targeted therapy-based treatment is recommended, with options including trastuzumab deruxtecan (T-DXd) and tucatinib plus trastuzumab plus capecitabine 1, 2, 5, 6

If a patient finished trastuzumab-based adjuvant treatment ≤12 months before recurrence, second-line HER2-targeted therapy-based treatment recommendations should be followed 2, 4
If a patient finished trastuzumab-based adjuvant treatment >12 months before recurrence, first-line HER2-targeted therapy-based treatment recommendations should be followed 2, 4

The American Society of Clinical Oncology states that ER-negative/PR-negative/HER2-positive breast cancer lacks hormone receptor expression, making endocrine therapy ineffective and inappropriate, and treatment must focus exclusively on HER2-targeted therapy combined with chemotherapy 1, 2, 4, 7