Neoadjuvant Therapy for HER2-Positive Breast Cancer

Introduction to Neoadjuvant Therapy

The National Comprehensive Cancer Network (NCCN) recommends neoadjuvant chemotherapy combined with HER2-targeted therapy for patients with Stage IIIA disease, particularly those with tumors ≥T2 or ≥N1 2.
Neoadjuvant therapy has emerged as the standard of care for locally advanced HER2-positive breast cancer, offering multiple advantages including tumor downstaging to enable surgical resection, early assessment of treatment response, and the potential for breast conservation in patients who would otherwise require mastectomy 1, 2.

The American College of Radiology (ACR) recommends breast ultrasound as the primary imaging modality for initial detection and follow-up assessment in young women with dense breast tissue 1.
The NCCN guidelines note that breast ultrasound is not a validated screening modality and does not replace mammography for early detection of breast cancer 1.

The NCCN panel recommends AC followed by docetaxel plus trastuzumab as a standard regimen for HER2-positive disease 7.
The addition of trastuzumab to neoadjuvant chemotherapy has been shown to increase pathologic complete response rates from 26% to 65.2% in HER2-positive tumors 3.

The NCCN panel recommends up to 1 year of HER2-targeted therapy with trastuzumab 7.
Dual HER2 blockade with pertuzumab may be considered for patients with node-positive disease based on the updated APHINITY trial data 7.

The NCCN guidelines state that local therapy after a complete or partial response to preoperative systemic therapy usually consists of total mastectomy with level I/II axillary lymph node dissection, with or without delayed breast reconstruction, or lumpectomy and level I/II axillary dissection 6.
The decision between breast-conserving surgery and mastectomy should be based on tumor size, breast size, patient preference, and oncologic safety 1, 6.

The NCCN guidelines recommend endocrine therapy (category 1) in women with ER- and/or PR-positive tumors 7.
Radiation therapy is recommended based on prechemotherapy characteristics to the chest wall and supraclavicular lymph nodes 6, 4.
Trastuzumab emtansine (T-DM1) may be considered for patients with residual disease after neoadjuvant therapy based on the KATHERINE trial results [7].