Danielle Roman, PharmD, Allegheny Health Network, Pittsburgh, Pennsylvania, discussed the evolving management of hormone receptor–positive, HER2-positive metastatic breast cancer, at the 2025 Journal of the Advanced Practitioner in Oncology (JADPRO) meeting in National Harbor, Maryland.

Dr Roman highlighted novel strategies integrating endocrine therapy, HER2-targeted agents, and emerging CDK4/6 inhibitors such as palbociclib and abemaciclib, supported by key trials including DESTINY-Breast09 and PATINA. 

Transcript:

Hello, my name is Danielle Roman. I'm an oncology clinical pharmacist at Allegheny Health Network in Pittsburgh, Pennsylvania. I presented at JADPRO Live along with my colleague Kaitlyn Reeder, who is a physician's assistant at Allegheny Health Network in Pittsburgh.

We presented on the topic of hormone-receptor positive, HER2-positive metastatic breast cancer, what we also call our “triple-positive” breast cancer population. We discussed some of the novel therapies and multidisciplinary strategies that are in place to manage these patients. Some of the early discussion we had during the conference was looking at the incidence of this subtype and I think one of the important things to point out is, of our patient population that is HER2-positive, about 50% of those patients are also hormone receptor-positive, so really a pretty significant patient population with this particular breast cancer subtype and survival here is somewhat limited, particularly as we look at that patient population with metastatic or distant disease, the 5-year survival here is just under 50%, definitely showing some work that needs to be done in order to improve survival for these patients.

We did an overview of the HER2 receptor. The fact that it is over expressed or amplified in about 20% of patients with breast cancer and it has typically been associated or considered a poor prognostic feature, but now that we have therapies targeting HER2, that has really revolutionized this area and improved outcomes for these patients dramatically. We reviewed a bit of the testing for HER2 done historically through immunohistochemistry, or IHC, and then reflexing to in situ hybridization, or ISH, if needed in select patients and we reviewed how to determine HER2 positivity versus negativity. 

Again, our focus was really on those HER2-positive patient populations. We also went through some of the overview of treatment here and as we consider that these patients are hormone receptor-positive and HER2-positive, they're often candidates for a number of different therapies including endocrine therapies, our targeted therapies in the form of HER2 targeted therapies. But we now have some data also in using the CDK4/6 inhibitor class in select patients and then also a role for chemotherapy here.

We went through the different types of HER2 targeting therapies. We have our monoclonal antibodies, we have our tyrosine kinase inhibitors as well as our antibody drug conjugates, in particular, this class has really revolutionized treatment here with patients with HER2-positive disease. We also discussed just an overall treatment algorithm and the fact that there are options for the treatment of these patients. 

The historic standard has been chemotherapy in combination with HER2-targeted therapy. This is typically given for a certain duration of cycles, really the kind of induction cycles that is usually somewhere around 6 to 8 cycles of the chemotherapy. For patients that have reached a good response, chemotherapy is often discontinued at this point and patients may continue on with their HER2-targeting maintenance therapy and often endocrine therapy is added at this point because we are not giving the endocrine therapy concurrent with chemotherapy in the vast majority of situations.

The other option here is using endocrine therapy in combination with HER2-targeted therapies. This is particularly in a patient population where maybe you are looking to stay away from chemotherapy. These are patients that maybe have poor performance status or comorbidities that preclude the use of chemotherapy as this option is really not seen as a current standard of care, but certainly there is data to support doing this and may be considered in a subset of patients.

Finally, an option that is typically not employed, but that would be sort of our third option, which is endocrine therapy alone. Really limited application here, but maybe a consideration for select patients with low disease burden or contraindications to giving HER2 targeted therapies, such as those patients with CHF.

We also reviewed some of the core clinical trials that have changed this field recently. One of those is the DESTINY-Breast09 trial. That has challenged our historic standard chemotherapy, HER2 targeting therapy approach in that first line setting. This was a trial that looked at antibody drug conjugate trastuzumab deruxtecan, either alone or in combination with pertuzumab and compared it to the historic standard of THP, an improvement in median progression-free survival compared to the TDxd, or trastuzumab deruxtecan plus pertuzumab, when compared to historic standard of care. The TDxd-alone arm results have not been reported yet, but I think this is a promising approach that we may start to see integrated into practice soon.

We also discussed some of the limited data that supports the CDK4/6 inhibitor class here. This would be the recently reported PATINA trial.This is looking at the addition of palbociclib to endocrine therapy and HER2-targeted therapy for patients in the metastatic setting. After they have received their induction chemotherapy, that has been completed and patients are progressing onto maintenance therapy, an improvement in median progression-free survival with the addition of palbociclib here. This is the first major inclusion of the CDK4/6 inhibitor class for those patients with HER2-positive disease.

We briefly discussed the monarchER trial, which is also looking at a CDK4/6 inhibitor abemaciclib. This was looked at in combination with endocrine therapy and trastuzumab and did find here an improvement in median progression-free survival with the addition of abemaciclib.

We also did a brief review of adverse effect profile as we know this is a really important part of our strategy to keep our patients on therapy. We reviewed some of this core HER2-targeting therapy, adverse effects that may be seen such as cardiotoxicity, and we discussed ways of monitoring for this and managing, really just want to highlight here that is generally a reversible cardiac toxicity and patients generally are managed appropriately for heart failure and oftentimes are able to continue on therapy with appropriate medication management. 

We also discussed diarrhea as an adverse effect that we can see, particularly with the HER2-targeting tyrosine kinase inhibitors such as neratinib or lapatinib, tucatinib. We discussed some of the management strategies here with just general management of diarrhea as well as our antidiarrheal strategies and also we can see a diarrhea with pertuzumab, so we discussed this adverse effect as well. Finally, we did a brief overview of palbociclib adverse effects and really covered here, the major one being neutropenia, and a discussion of how we can manage that.

Source:

Roman D, Reeder K. Novel Therapies and Multidisciplinary Strategies in Metastatic Triple-Positive Breast Cancer. Oral Presentation. Presented at the 2025 Journal of the Advanced Practitioner in Oncology Meeting. October 23-26, 2025; National Harbor, Maryland.