Q&A: Prioritizing QOL Important to Treating HR+, HER2- Metastatic Breast Cancer

Testing with liquid biopsies can help determine how to treat HR+, HER2- breast cancer.

The second-line treatment of mutated hormone receptor (HR)-positive, HER2-negative metastatic breast cancer can become more complex when considering the potential of mutated cancer.

John Novak, PA-C, of the University of Colorado Medicine, led a Community Case Forum with Oncology Nursing News regarding how to address treatment for patients with HR-positive, HER2-negative metastatic breast cancer.

What was the focus of discussion at the forum?

Novak: The overall premise of the forum…was the evolving second-line treatment landscape, and hormone receptor-positive, HER2-negative, metastatic breast cancer. Basically, we focused on how to approach that patient who progresses on first-line endocrine therapy…. And something that's really important is, our people, our providers, doing molecular profiling or molecular testing to determine if the patient has a new or acquired mutation that we can potentially target. Two really important targets that are acquired when this type of breast cancer is exposed to endocrine therapy is ESR1 and PI3KCA and the treatments are a little bit different.

The focus…No. 1, is testing being done?… And No. 2, if they have an ESR1 mutation, how would you treat that patient? And elacestrant (Orserdu) is an oral selective estrogen receptor degrader that…is indicated for patients who…develop an ESR1 mutation. Then kind of the second thought process was, “OK, if someone has a co-mutation, if a patient has a co-mutation, ESR1 mutation and a PI3KCA mutation, which target would you focus on?”… Because the treatments are a little bit different. So the patient who has a PI3KCA mutation, per se, would be treated with fulvestrant (Faslodex), which is an injectable SERD, plus alpelisib (Piqray), which is a drug that targets PI3KCA.

How do you decide whether to focus on targeting ESR1 or PI3KCA mutations in treatment?

Novak: One of the big factors is tolerability, or the [adverse] effect profile. I think everyone was in agreement that elacestrant is a much better-tolerated medication or treatment overall compared to the PI3KCA inhibitor…. The other factor is that you know elacestrant is an oral drug that you take every day, whereas the other 2 regimens require a patient to come into the clinic every 4 weeks to get an injection in addition to the oral medication that targets PI3KCA.

What should providers know when making treatment decisions about HR-positive, HER2-negative breast cancer with potential mutations?

Novak: The biggest takeaway is doing the appropriate molecular testing or molecular profiling, which is a liquid biopsy, to see if a patient has developed one of these acquired mutations, because that is going to have a huge impact on how we treat that patient. So that would be the most important takeaway, that providers are doing testing with every progression.

The second big takeaway is [adverse] effect profile and what everyone was in agreement [about was] if a patient has a targetable mutation, it's much better to go with the treatment that targets that than use something like, say, chemotherapy, or some of the ADCs [antibody-drug conjugates], which have greater toxicities, even though they may be more effective, like the (ADC).… They have a lot more [adverse] effects,…the efficacy data is amazing, but it's also a much harder treatment to tolerate.

Why is prioritizing AE profiles important when treating patients with HR-positive breast cancer?

Novak: The treatment of hormone receptor-positive metastatic breast cancer—it's a different beast. It responds very well to anti-estrogen therapies. It's less aggressive, so it's more of a marathon than a sprint. We want to get as much mileage as possible out of the targeted therapies, before going onto something more aggressive, such as IV chemotherapy or an [ADC].

… Patients who are on first-line treatment, say, with fulvestrant and a CDK4/6 inhibitor, oftentimes they're going to be on that medication for 3 to 5 years without progressing. And so they're kind of used to being on a treatment that has minimal [adverse] effects. There are several good options that we can [use to] target what's driving the growth of the cancer, but also minimizes these [adverse] effects and maintain quality of life, because quality of life is paramount.

This transcript has been edited for clarity and conciseness.