HER2+ Breast Cancer
Identifying Candidates for Neoadjuvant or Adjuvant Anti-HER2 Therapy
Individualizing therapy for patients with human epidermal growth factor receptor 2–positive (HER2+) breast cancer currently involves the consideration of such factors as tumor size, nodal status, and response to neoadjuvant therapy. Ongoing trials are exploring newer strategies for neoadjuvant and adjuvant therapies to further optimize the paradigm.
Chief, Division of Breast Oncology
“For a patient who is newly diagnosed with HER2+ breast cancer and has a tumor that is larger than 2 cm in size, or if they have lymph node involvement, I generally recommend preoperative therapy followed by surgery, and then we would see what is found at the time of surgery and tailor adjuvant therapy based on this.”
For a patient who is newly diagnosed with HER2+ breast cancer and has a tumor that is larger than 2 cm in size, or if they have lymph node involvement, I generally recommend preoperative therapy followed by surgery, and then we would see what is found at the time of surgery and tailor adjuvant therapy based on this. It is really important that we administer treatment prior to the surgery in this case so that we can understand how the tumor responds to it, which helps us to choose the best adjuvant treatment for them, since the response to neoadjuvant therapy shows how sensitive their cancer is to treatment.
For patients with stage II or III disease, we give neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab (known as the TCHP regimen) for 6 cycles. If the patient has a pathologic complete response to therapy, I usually give them adjuvant trastuzumab and pertuzumab to complete a total of 1 year of HER2-directed therapy. If, on the other hand, we find residual disease at the time of surgery (ie, the TCHP did not eradicate the cancer), we would proceed with a different approach. Based on data from the phase 3 KATHERINE trial, we would switch their therapy to trastuzumab emtansine (T-DM1) for 14 cycles.
Patients with tumors that are smaller than 2 cm and with no lymph node involvement were excluded from the initial pivotal trials of adjuvant trastuzumab because it was felt that they were at lower risk. And, while these individuals do have a favorable prognosis, retrospective data suggest that, if they do not receive systemic therapy, their risk of recurrence might be as high as 20% to 30%. Data to guide treatment for patients with stage I HER2+ disease come from the APT trial, which showed that 12 weeks of adjuvant paclitaxel plus trastuzumab (TH) was associated with excellent 10-year outcomes and very few distant recurrences. Further, the phase 2 ATEMPT trial looked at 1 year of adjuvant T-DM1 therapy and showed excellent 5-year outcomes that are consistent with APT. So, I think that either TH or T-DM1 is an appropriate treatment option for patients with stage I HER2+ breast cancer.
Those are the general paradigms that we think about, and there are a lot of ongoing trials in this setting. Such studies include those for patients with residual disease, such as the CompassHER2 RD and the DESTINY-Breast05 trials. There is also the ongoing DESTINY-Breast11 trial, which is comparing neoadjuvant trastuzumab deruxtecan (T-DXd) monotherapy or T-DXd followed by paclitaxel, trastuzumab, and pertuzumab (THP) with TCHP. There are also trials looking to tailor the preoperative regimen, including CompassHER2-pCR, which is giving preoperative THP followed by adjuvant trastuzumab and pertuzumab for patients who achieve a pathologic complete response. Looking to the future, I think that these trials will lead to changes in the neoadjuvant and adjuvant treatment of HER2+ breast cancer, and I am hopeful that we will continue to develop and refine predictive biomarkers that will enhance our ability to tailor treatments to individual patients.
ClinicalTrials.gov. CompassHER2-pCR: decreasing chemotherapy for breast cancer patients after pre-surgery chemo and targeted therapy. Updated June 22, 2023. Accessed September 5, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04266249
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