Neoadjuvant therapy for patients with HER2-positive breast cancer
- William M Sikov, MD, FACP
William M Sikov, MD, FACP
- Associate Professor of Medicine
- Obstetrics and Gynecology
- Warren Alpert Medical School of Brown University
Persistent activation of signaling pathways as a result of amplification of the human epidermal growth factor receptor 2 (HER2) in patients with HER2-positive breast cancer leads to a biologically aggressive malignancy with heightened sensitivity to cytotoxic chemotherapy. Compared with most other subtypes of breast cancer, a higher percentage of HER2-positive patients achieve a pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT), even in the absence of HER2-targeted therapy [1,2]. Using targeted therapy to block activation of those pathways further enhances the chemosensitivity of HER2-positive breast cancer, increasing the pCR rate. Clinical trial results from the last few years suggest that newer HER2-targeted agents may allow more effective inhibition of HER2 and expand options for the NACT regimen administered with HER2-targeted therapy based on the patient’s risk factors and overall medical condition.
This topic will review issues pertaining specifically to administration of neoadjuvant therapy in patients with HER2-positive breast cancer. General principles of neoadjuvant chemotherapy, including patient selection for neoadjuvant therapy, assessment of response to therapy, and surgical management after neoadjuvant chemotherapy, are discussed in detail elsewhere. (See "General principles of neoadjuvant therapy for breast cancer".)
Adjuvant treatment for patients with HER2-positive disease who have received neoadjuvant treatment is also discussed elsewhere. (See "Adjuvant systemic therapy for HER2-positive breast cancer", section on 'Patients who were treated with neoadjuvant therapy'.)
Neoadjuvant chemotherapy (NACT) is appropriate for many patients with locally advanced breast cancer regardless of subtype, because a response may allow both less aggressive surgery and improved surgical outcomes. We generally define locally advanced as stage III cancers as well as the subset of IIB cancers with T3 disease. In addition, patients with earlier-stage, HER2-positive disease (stage I or II) may also be candidates for neoadjuvant therapy if they meet any of the following criteria:
●The patient desires breast-conserving surgery (BCS) but is not a candidate for BCS or is likely to have a suboptimal cosmetic outcome with BCS due to tumor location or size relative to the size of the patient’s breast, and may be a better candidate if neoadjuvant therapy decreases the extent of her tumor.
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- OUTCOME MEASURES
- COMPONENTS OF THERAPY
- - Standard regimens
- Anthracycline-based treatment
- Nonanthracycline-based treatment
- Choice of taxane
- - Alternatives for those with low-risk disease or comorbidities
- Biologic therapy
- - Trastuzumab
- - Pertuzumab
- - Investigational approaches
- Lapatinib with chemotherapy
- HER2-targeted therapy without chemotherapy
- Other agents
- TIMING OF HER2-DIRECTED AGENTS
- TUMOR PROGNOSTIC FEATURES
- EVALUATION OF RESPONSE AND SURGICAL MANAGEMENT
- ADJUVANT THERAPY AFTER NEOADJUVANT THERAPY
- SUMMARY AND RECOMMENDATIONS