The Importance of Right Sizing Early HER2 Breast Cancer Treatment

Sara Hurvitz, MD, University of California, Los Angeles, California, discusses the importance of right sizing early HER2 treatment for patients with HER-positive breast cancer, a topic she presented at the 2022 Great Debates and Updates in Women's Oncology virtual meeting.

In her presentation, Dr Hurvitz highlighted the current established treatments for early HER2 breast cancer, which have been shown to significantly improve patient outcomes. She also looked ahead to potential future treatments currently in clinical trials.

Transcript:

Hi, I'm Dr Sara Hurvitz, professor of medicine at the University of California, Los Angeles, at the Jonsson Comprehensive Cancer Center. I spoke about right sizing early HER2 treatment. The treatment of HER2-positive breast cancer has certainly evolved very rapidly, especially in the last 10 years or so, with the availability of several HER2-directed therapies. Currently we have 4 HER2-directed therapies available for early-stage disease, and we know that the use of HER2-directed therapies has significantly improved outcomes for patients with this subgroup of breast cancer that has poor disease prognosis.

However, it's become increasingly difficult to figure out how much therapy is needed for a given patient. We certainly don't want to overtreat a patient who could do just as well with less therapy. And when you look at the data regarding how many patients are diagnosed with very early stage HER2-positive breast cancer, it turns out that most patients have stage 1 or 2 breast cancer when they're diagnosed with HER2-positive breast cancer. It's not as it was back in the '90s or even early 2000s, where patients would often come in with locally advanced HER2-positive breast cancer. Due to screening guidelines, et cetera, we are picking up cancers earlier, and the majority of HER2-positive breast cancers are early stage.

That said, stage-for-stage, HER2-positive breast cancer does worse than HER2-negative breast cancer, even for non-negative stage 1 tumors. We do think that some form of systemic therapy is likely beneficial regardless of size of tumor. The use of neoadjuvant therapy has become standard now for many of our cancers. This is because we know that the response to therapy is both prognostic and predictive of benefit from adjuvant [trastuzumab emtansine] T-DM1, which is available now to our patients who have residual disease after standard neoadjuvant treatment.

In my own patients, if the tumor is 1.5 centimeters or greater, or node positive, I will start with neoadjuvant therapy. If they have residual disease, they will receive T-DM1. Most of my patients receive trastuzumab, pertuzumab and non-anthrocycline chemotherapy in the neoadjuvant setting, given the very high pathological complete reponse rates associated with this and the lack of any convincing evidence that anthrocyclines are needed to improve outcomes for patients. For patients with high-risk disease, we have the use of neratinib now in the extended adjuvant setting. This drug can cause a fair amount of diarrhea, so most of us are using a dose escalation strategy over the first 2 weeks of therapy to start low with the neratinib dose and escalate over 2 weeks and use loperamide as needed to help mitigate that.

The treatment of early-stage disease may quickly change with studies like the CompassHER2-RD, ASTEFANIA, and DESTINY-Breast05 trials, all looking at novel agents in high-risk early-stage disease, including tucatinib, atezolizumab, and [trastuzumab deruxtecan] T-DXd respectively.

And I think that although we've seen a number of trials looking at whether we can reduce the amount of chemotherapy or omit chemotherapy in the neoadjuvant setting for HER2-positive disease, the standard of care remains taxane-based chemotherapy in the neoadjuvant setting, most commonly the TCHP regimen, although there is promising evidence supporting the use of paclitaxel with HP in the adjuvant setting, and some will use that in the neoadjuvant setting if a patient has comorbidities that would make the full TCHP regimen difficult or dangerous for a patient to receive.

In summary, the therapeutic strategies available for patients with early stage HER2-positive breast cancer are rapidly evolving. We currently have available several treatment strategies for patients and multiple trials that can help us fine tune how much therapy to use for a given patient. Increasingly, we are using the neoadjuvant setting to interrogate the sensitivity of a tumor to the systemic therapy that we're choosing. And in the most common scenario, we are avoiding anthrocyclines for most patients with this subtype of breast cancer. In the next 1 or 2 years, I think we're going to see results from many ongoing trials that may further finetune how we treat this disease. Thanks.

Source:

Hurvitz, S. Right Sizing Early HER2 Treatment. Presented at: Great Debates & Updates in Women’s Oncology. Sep 21-23, 2022. Virtual.