From the Guidelines
Chemotherapy for stage 1 HER2-positive breast cancer should involve a combination of HER2-targeted therapy and chemotherapy, with paclitaxel and trastuzumab being a preferred option for patients with low-risk, T1,N0,M0, HER2-positive disease. This approach is based on the most recent evidence from the NCCN clinical practice guidelines in oncology, version 3.2024 1, which reports a 3-year rate of DFS of 98.7% and a low risk of serious toxic effects with this regimen. The treatment typically involves chemotherapy for 3-6 months with HER2-targeted therapy continuing for a full year. Some key points to consider include:
- The use of trastuzumab with chemotherapy is a category 1 recommendation in patients with HER2-positive tumors larger than 1 cm, as shown in the 2009 NCCN guidelines 1.
- For smaller tumors (less than 1 cm) without lymph node involvement, paclitaxel with trastuzumab weekly for 12 weeks, followed by trastuzumab alone to complete a year of HER2-targeted therapy, may be considered, as mentioned in the 2018 ASCO clinical practice guideline focused update 1.
- Regular cardiac assessments are performed every 3 months during therapy to ensure heart function remains stable, as recommended in the 2014 NCCN guidelines 1.
- The TCH protocol (docetaxel, carboplatin, and trastuzumab) or TCHP which adds pertuzumab (Perjeta) are also common regimens used in the treatment of stage 1 HER2-positive breast cancer. Overall, the choice of chemotherapy regimen should be individualized based on the patient's risk factors, comorbidities, and tumor characteristics.
From the FDA Drug Label
Patients were randomized (1:1) to receive doxorubicin and cyclophosphamide followed by paclitaxel (AC → paclitaxel) alone or paclitaxel plus trastuzumab (AC → paclitaxel + trastuzumab). Trastuzumab was administered at 4 mg/kg on the day of initiation of paclitaxel and then at a dose of 2 mg/kg weekly for a total of 52 weeks In HERA, breast tumor specimens were required to show HER2 overexpression (3+ by IHC) or gene amplification (by FISH) as determined at a central laboratory Patients with node-negative disease were required to have ≥ T1c primary tumor. Trastuzumab was administered with an initial dose of 8 mg/kg followed by subsequent doses of 6 mg/kg once every three weeks.
The use of trastuzumab in combination with chemotherapy is supported for patients with HER2-positive breast cancer, including those with stage 1 disease.
- Key points:
- Trastuzumab can be administered weekly or every 3 weeks.
- Chemotherapy regimens may include doxorubicin, cyclophosphamide, paclitaxel, docetaxel, and carboplatin.
- Patients with node-negative disease may be eligible for trastuzumab treatment if they have high-risk features. 2
From the Research
Treatment Options for Stage 1 HER2-Positive Breast Cancer
- The use of trastuzumab in combination with chemotherapy has been shown to improve survival outcomes in patients with HER2-positive early-stage breast cancer 3.
- A study published in 2021 found that a weekly regimen of paclitaxel and carboplatin with trastuzumab and pertuzumab achieved a high pathologic complete response rate in patients with stage II-III HER2-positive breast cancer, with fewer toxicities compared to other regimens 4.
- Another study from 2006 found that the addition of carboplatin to paclitaxel and trastuzumab improved objective response rate and progression-free survival in women with HER2-overexpressing metastatic breast cancer 5.
Chemotherapy Regimens
- The optimal treatment of early-stage HER2-positive breast cancer involves the use of trastuzumab in combination with standard chemotherapy regimens 6.
- A phase II trial found that gemcitabine/carboplatin with or without trastuzumab was highly active in patients with metastatic breast cancer, with significant preclinical synergy and synergistic antitumor activity 7.
Considerations for Treatment
- The decision to initiate trastuzumab therapy should be carefully considered due to the increased risk of cardiotoxicity associated with its use 3.
- Different subgroups of patients with HER2-positive breast cancer may benefit from different therapeutic approaches, and there is ongoing work to optimize and de-escalate treatment in patients who may do just as well with less therapy 6.