From the Guidelines
Anti-HER2 therapy after surgery is recommended for patients with HER2-positive breast cancer to reduce recurrence risk, with the standard regimen including trastuzumab administered every three weeks at 6 mg/kg for a total duration of one year, as supported by the most recent guidelines from 2024 1.
Key Considerations
- For higher-risk patients, particularly those with node-positive or hormone receptor-negative disease, adding pertuzumab at 420 mg every three weeks for one year provides additional benefit, as shown in the APHINITY trial 1.
- Patients with small (≤2 cm), node-negative tumors may receive a shorter course of trastuzumab with paclitaxel for 12 weeks (the APT regimen) 1.
- For patients with residual disease after neoadjuvant therapy, T-DM1 at 3.6 mg/kg every three weeks for 14 cycles is preferred instead of trastuzumab, as recommended by the ESMO guidelines 1.
- Regular cardiac monitoring with echocardiograms every 3 months is essential during treatment due to potential cardiotoxicity, as emphasized in the guidelines 1.
Treatment Regimens
- Trastuzumab: 6 mg/kg every three weeks for a total duration of one year, with an initial loading dose of 8 mg/kg.
- Pertuzumab: 420 mg every three weeks for one year, for higher-risk patients.
- T-DM1: 3.6 mg/kg every three weeks for 14 cycles, for patients with residual disease after neoadjuvant therapy.
Important Notes
- The treatment regimen should be individualized based on the patient's risk factors, tumor characteristics, and overall health status, as recommended by the guidelines 1.
- The guidelines emphasize the importance of regular cardiac monitoring and careful consideration of the potential benefits and risks of anti-HER2 therapy in each patient, as supported by the studies 1.
From the FDA Drug Label
Patients were randomized (1:1:1) upon completion of definitive surgery, and at least four cycles of chemotherapy to receive no additional treatment, or one year of trastuzumab treatment or two years of trastuzumab treatment. Trastuzumab was administered with an initial dose of 8 mg/kg followed by subsequent doses of 6 mg/kg once every three weeks. The major efficacy outcome measure was Disease-Free Survival (DFS), defined as in NSABP B31 and NCCTG N9831 A protocol specified interim efficacy analysis comparing one-year trastuzumab treatment to observation was performed at a median follow-up duration of 12. 6 months in the trastuzumab arm. Based on this analysis, extending trastuzumab treatment for a duration of two years did not show additional benefit over treatment for one year [Hazard Ratios of two-years trastuzumab versus one-year trastuzumab treatment in the intent to treat (ITT) population for Disease-Free Survival (DFS) = 0.99 (95% CI: 0.87,1.13), p-value = 0.90 and Overall Survival (OS) = 0.98 (0.83,1.15); p-value = 0. 78].
Trastuzumab treatment after surgery for HER2-positive early breast cancer (EBC) patients is recommended for one year. The treatment regimen consists of an initial dose of 8 mg/kg followed by 6 mg/kg every three weeks.
- Key points:
- Trastuzumab treatment should be started after completion of definitive surgery and at least four cycles of chemotherapy.
- The treatment duration is one year, as extending it to two years does not show additional benefit.
- Patients with ER+ and/or PR+ tumors should receive hormonal therapy.
- Radiation therapy, if administered, should be initiated after completion of chemotherapy. 2
From the Research
Anti-HER2 Treatment After Surgery
- The availability of HER2-targeted therapy has dramatically improved patient outcome in HER2-positive early breast cancer, as demonstrated by the EBCTCTG meta-analysis on trastuzumab in HER2+ EBC 3.
- Adding trastuzumab to chemotherapy has reduced recurrence rates and breast-cancer related mortality by a third 3.
- For patients with non-pCR, 14 cycles of adjuvant T-DM1 have become a new adjuvant therapy standard based on the results of the KATHERINE trial 3.
- Primary surgery can be offered to patients with low tumor burden (cN0 cT1), and 12 weeks of adjuvant paclitaxel + trastuzumab for one year are correlated with excellent outcome based on the APT trial results 3.
Adjuvant Treatment of HER2-Positive Breast Cancer
- Trastuzumab was the only approved HER2-targeted therapy in the adjuvant setting in 2012, and data from five randomized clinical trials showed significant improvements in disease-free and overall survival (DFS/OS) 4.
- A trastuzumab-containing regimen for up to 1 year is now considered standard for all patients with HER2-positive tumors larger than 1 cm in size who would have fulfilled eligibility to those studies 4.
- Pertuzumab, a recombinant humanized monoclonal antibody that binds to the extracellular dimerization domain II of HER2, was recently approved for adjuvant therapy and neoadjuvant therapy of HER2-positive early breast cancer 5.
Treatment Options and Sequencing
- The current standard first-line therapy for patients with HER2+ metastatic breast cancer (MBC) is a taxane combined with trastuzumab and pertuzumab 6.
- Trastuzumab deruxtecan should be used preferentially in the second line, with the only caveat being patients with CNS involvement where the tucatinib, capecitabine, and trastuzumab regimen could be considered 6.
- In the third line setting, given the survival benefits demonstrated with the tucatinib regimen in patients with and without CNS metastases, this is the preferred strategy 6.