Wassim McHayleh, MD, MBA, FACP: Hello, and welcome to this Pharmacy Times® Practice Pearls program titled “Targeted Treatment of HR+/HER2- Breast Cancer.” My name is Wassim McHayleh, and I’m the clinical program director of breast oncology at AdventHealth Cancer Institute in Orlando, Florida. Joining me in this discussion is Dr Alisa Vinokurov, a clinical oncology pharmacist with AdventHealth Medical Group in Orlando as well. We’re going to talk about HR [hormone receptor]–positive, HER2-negative breast cancer with a focus on treatment strategies and future directions in the treatment. Let’s get started.

When we’re treating HR-positive, HER2-negative breast cancer, the first and most important thing is disease stage, as the treatment goals depend on the stage. If the patient has early stage disease, then treatment would consist of surgery in combination with radiation therapy plus or minus chemotherapy. The treatment choices depend on patient age.

In our discussion, we’re going to focus more on metastatic or stage IV breast cancer. Patient age and comorbid conditions play a very important role in the treatment, as older patients aren’t going to be candidates for certain therapies, and certain conditions don’t allow patients to receive particular treatments. Another important factor in deciding on the treatment is the molecular profile. For example, for a hormone-positive breast cancer, if they carry a PIK3CA mutation, they would be candidates for particular targeted therapies, such as Piqray [alpelisib].

Mutation testing or molecular testing for PIK3CA or ESR mutations in hormone-positive breast cancer should be ordered initially as soon as possible when treating metastatic disease. I wouldn’t proceed with testing for early stage disease, but for stage IV breast cancer, whenever I have tissue early in the treatment, I would send the testing. It allows me to draw the treatment plan ahead of time. For example, if there’s a PIK3CA mutation, that allows us to plan the appropriate treatment. Whether the patient carries an ESR mutation [also helps us] choose the appropriate hormone therapy.

As far as when and how these tests are performed, we usually perform them on tissue samples. Either we go back to the initial biopsy, whether it’s tissue from previous biopsy, or to a fresh biopsy at the time of recurrence or progression. It could be challenging to perform molecular testing on bone samples, especially because HR-positive, HER2-negative breast cancer could have only bone metastasis. This is a separate entity in which molecular testing could be challenging. In case of lack of tissue, we could always perform liquid biopsies, which aren’t going to be as thorough but will still help guide our treatment plan.

The clinical end points that are important when monitoring response to therapy, especially when we’re talking about metastatic disease, could be PFS [progression-free survival], overall survival, and overall response rate. It’s also important to monitor the safety profile of every treatment option. It also depends on the patient’s age, disease burden, and symptoms. For example, if a patient has an organ compromised with massive liver metastases or symptomatic disease, then you care very much about the overall response rate because that will provide disease control and relief.

For a patient who has small disease burden, you’re going to be more focused on their overall survival and progression-free survival. How can you slow the disease and make them live longer? Those decisions depend case by case on where you set your priorities. Alisa knows this in her practice in our clinic, and she sees how we make changes and don’t use the same treatment for 2 different patients. We personalize the treatment based on those particular goals.

Transcript edited for clarity.