Biomarker Testing Is Essential in HR-Positive Metastatic Breast Cancer

Patients with hormone receptor (HR)-positive metastatic breast cancer can expect to undergo biomarker testing multiple times throughout their treatment experience to ensure that they are getting the best therapy for their individual disease, according to Dr. Jennifer Matro.

“Metastatic breast cancer of all subtypes presents challenges because each cancer and each patient are unique,” Matro said in her presentation at CURE®’s Educated Patient® Metastatic Breast Cancer Summit.

Matro is the clinical service chief, co-leader of the Breast Disease team and associate clinical professor of Medicine at the University of San Diego in California. At the summit, she discussed updates in HR-positive metastatic breast cancer, which can include estrogen receptor (ER)-positive and progesterone receptor (PR)-positive disease.

Biomarkers Help Determine Initial Treatments

At the initial time of diagnosis, Matro explained, patients can expect to undergo testing for the existence of certain hormones (estrogen and progesterone) in their cancer, as well as for certain proteins or genetic changes — commonly referred to as biomarkers — such as HER2.

“[Biomarkers] can be useful to show what treatment is likely to work for your cancer. They can also show what treatment is unlikely to work for your cancer,” Matro said. “We can find them by testing both blood and [tumor] tissue.”

Upfront biomarker testing typically looks for BRCA or BRAF mutations, NTRK fusions, PIK3CA fusions or DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) status, which occurs when cells’ replication function does not work properly.

Typically, the first line of therapy for ER-positive, HER2-negative metastatic breast cancer includes a drug that blocks or eliminates the estrogen driving the cancer, as well as a targeted medication that works by specifically targeting one of the biomarkers that was revealed during initial biomarker testing.

“Most of the time, we’re combining these hormone therapies with CDK4/6 inhibitors — (Ibrance [Palbociclib]), (Kisqali [ribociclib]) or (Verzenio [abemaciclib]).”

Clinicians and patients should consider multiple aspects before deciding on which CDK4/6 inhibitor is best for the patient, including previous breast cancer treatments, if any; menopausal status; side effects associated with the treatments; and how the medication is taken.

“And unfortunately, in the United States, health insurance does dictate. If we have equivalent drugs, sometimes insurance will tell us that we have to use one over another,” Matro said.

When Metastatic Breast Cancer Progresses on Frontline Therapy

“Cancers develop drug resistance over time that the cells learn to adapt, and essentially tolerate or grow through the therapy,” Matro said.

After the start of treatment, metastatic breast cancer cells can develop genetic mutations that make them resistant to certain therapies. These mutations include PIK3CA, AKT, PTEN and ESR1. However, there are now treatment options that exist in this space that can bypass the genetic mutation and continue to kill off cancer cells.

If patients test positive for PIK3CA, AKT or PTEN, the next treatment options can include Vijoice (alpelisib) and Faslodex (fulvestrant) or Truqap (capivasertib) and Faslodex, Matro explained. Conversely, if, upon progression, the disease tests positive for an ESR1 mutation, the next best treatment option may be Orserdu (elacestrant).

Finally, Matro explained that if patients do not test positive for any mutations after disease progression, the typical treatment is Faslodex plus a different CDK4/6 inhibitor or Afinitor (everolimus).

“One of the advances in breast cancer, in general, has been that we've, in many cases, turned this into a chronic disease where you're on in medicine for a while until the cancer adapts, and then we switch to something different to control it, hopefully for a long period of time.”

Editor's note: This program was made possible with support from Daiichi Sankyo Inc.

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