From the Guidelines
Patients with HER2-positive breast cancer and a tumor size greater than 2 centimeters should be treated with neoadjuvant systemic therapy with a taxane plus trastuzumab and pertuzumab, followed by surgery and adjuvant treatment with trastuzumab and pertuzumab for 1 year. This approach is supported by the most recent and highest quality study, which recommends neoadjuvant systemic chemotherapy with anti-HER2 therapy comprising pertuzumab and trastuzumab for patients with clinical stage II-III HER2-positive breast cancer (e.g. T >2 cm or node positive) 1.
Key Components of Treatment
- Neoadjuvant systemic therapy with a taxane (such as paclitaxel or docetaxel) plus trastuzumab and pertuzumab for 3-4 months
- Followed by an anthracycline-based regimen (such as doxorubicin with cyclophosphamide) for 2-3 months
- Surgery (lumpectomy or mastectomy with sentinel lymph node biopsy or axillary lymph node dissection depending on nodal status)
- Adjuvant treatment with trastuzumab and pertuzumab for 1 year
- Radiation therapy is typically recommended after lumpectomy or for high-risk post-mastectomy patients
- For hormone receptor-positive disease, endocrine therapy should be added for 5-10 years
Rationale for Treatment
The use of neoadjuvant systemic therapy with anti-HER2 therapy has been shown to achieve higher pathological complete response (pCR) rates and improve survival endpoints in patients with HER2-positive breast cancer 1. The addition of pertuzumab to trastuzumab in the adjuvant setting has also been shown to improve outcomes in patients with node-positive disease, regardless of hormone receptor status 1.
Special Considerations
- Patients with residual invasive disease after neoadjuvant chemotherapy and anti-HER2 therapy should receive adjuvant treatment with T-DM1 for up to 14 cycles 1
- Extended HER2-targeted therapy with neratinib for one year may be considered for high-risk, hormone receptor-positive patients 1
From the FDA Drug Label
Use in combination with trastuzumab and chemotherapy as neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer. PERJETA is indicated for use in combination with trastuzumab and chemotherapy for the neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer
The management of HER2-positive breast cancer with a tumor size greater than 2 centimeters is neoadjuvant treatment with pertuzumab in combination with trastuzumab and chemotherapy as part of a complete treatment regimen for early breast cancer 2, 2, 2.
- The treatment regimen includes pertuzumab, trastuzumab, and chemotherapy.
- Pertuzumab is administered as an intravenous infusion.
- The initial dose of pertuzumab is 840 mg, followed by 420 mg every 3 weeks.
- Trastuzumab and chemotherapy are also administered every 3 weeks.
From the Research
Management of HER2-Positive Breast Cancer
- The management of HER2-positive breast cancer with a tumor size greater than 2 centimeters typically involves neoadjuvant therapy, which is a standard of care in this setting 3.
- Neoadjuvant treatment with a combination of sequential chemotherapy and HER2-targeted therapy is currently the standard of care, followed by breast surgery, radiotherapy, completion of 12 months of HER2-directed therapy, and endocrine adjuvant therapy if necessary 3.
Neoadjuvant Therapy Regimens
- One study compared the efficacy of neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer, and found that traditional neoadjuvant systemic chemotherapy plus dual HER2-targeted blockade resulted in significantly more patients achieving a pathological complete response 4.
- Another study found that the combination of lapatinib and trastuzumab achieved a higher pathological complete response rate than trastuzumab alone in patients with HER2-positive early breast cancer 5.
- A real-world study from the National Institute of Oncology in Poland found that neoadjuvant pertuzumab plus trastuzumab in combination with docetaxel and carboplatin was effective in patients with HER2-positive breast cancer, with a particular emphasis on patients over 60 years of age 6.
Importance of Pathological Complete Response
- Achieving a pathological complete response is considered a good prognostic factor, particularly in patients with more aggressive breast cancer subtypes such as HER2-positive cancers 6, 7.
- The addition of trastuzumab to neoadjuvant chemotherapy roughly doubles the proportion of patients with HER2-positive breast cancer who achieve pathological complete response, and patients with pathological complete response show better prognosis compared with those with residual disease after neoadjuvant therapy 7.
Future Directions
- Translational studies are promising for further patient selection for HER2-targeted therapy and the development of a novel treatment strategy including PI3K-targeted therapy and immune checkpoint inhibitors 7.
- Feasibility studies to evaluate the ability of needle-biopsy to predict pathological complete response after neoadjuvant therapy suggested that standardization and refinements in biopsy procedure are essential for the design of clinical trials of omitted surgery for patients with radiologic complete response 7.