Using Knowledge to Steer Treatment Decisions in Metastatic Breast Cancer

Patients with estrogen receptor-positive (ER+), HER2-negative metastatic breast cancer may feel more empowered and prepared with the help of their care team, especially when making decisions about their treatments and throughout the journey itself, an expert said.

Dr. Jennifer M. Matro, medical oncologist and associate professor of medicine at UC San Diego Health, discussed the benefits of close monitoring from the care team, testing for a resistance mutation and knowing what questions to ask during a session of CURE® Educated Patient® Updates in Metastatic Breast Cancer.

Matro discussed this topic through a fictional patient named Jane, whose story represents many patients she sees in her practice. In particular, Jane has ER-positive, HER2-negative metastatic breast cancer that was initially diagnosed in 2022 and is considered de novo, meaning that this was her very first cancer diagnosis. Jane underwent hormone therapy and a CDK4/6 inhibitor, which Matro expressed a preference for an aromatase inhibitor.

"I think most of us would offer an aromatase inhibitor along with a CDK4/6 inhibitor just because it's a pill; it's easier to take than having to come in once a month for a fulvestrant (Faslodex) injection," she explained.

After 22 months of successful response, Jane's oncologist informed her that the current treatment was ineffective, prompting a recommendation for circulating tumor DNA (ctDNA) testing. Through this testing, care teams can analyze a blood sample to determine the status of a patient’s cancer. By studying ctDNA, clinicians may be able to identify specific genetic mutations in cancer cells, monitor a treatment’s effectiveness and track changes in the tumor over time without the need for biopsies, for example.

"We want to know if the cancer has developed a resistance mutation,” Matro said. “We can do the circulating tumor blood test to determine that." Specific mutations like ESR1 and PIK3CA are targeted, with Dr. Matro explaining, "If it turns out that [Jane] has an ESR1 mutation after having been on an aromatase inhibitor, there is a specific medication for that."

Matro mentioned that Jane went to speak with her care team with questions including the following:

• What is the extent of my disease progression?
• Could I have developed a resistance mutation?
• How common are ESR1 mutations? And when can they develop?
• What are the next steps after progressing on this treatment?
• When should I undergo a blood test for the cancer’s ESR1 mutation status?
• Have you tested for my ESR1 status before? And should we test again?

Matro noted that the importance of biomarker testing is stressed during this conversation, especially as Jane spent almost two years on an aromatase inhibitor, increasing the likelihood of developing a mutation.

Upon testing, Jane was confirmed to have developed an ESR1 mutation. Matro describes the testing process, stating, "The sample (is) a blood test (with) special tubes. You can't just go to a lab and say, ‘Do the circulating tumor DNA test.’" Jane's biomarker blood test results revealed the mutation, leading to the identification of a new treatment option – Orserdu (elacestrant).

Matro compares the decision to treat with either Faslodex or Orserdu, highlighting that Orserdu is more effective and easier to take in pill form. She presents data from the EMERALD trial, emphasizing the benefits of Orserdu in patients with ESR1 mutations, leading to Food and Drug Administration authorization for those with this specific mutation.

Findings from the EMERALD trial demonstrated superiority via median progression-free survival (the time after treatment when a patient has cancer without disease worsening) with Orserdu over standard hormone medications. Matro acknowledged the general trend that longer durations of the first treatment often lead to longer durations of the next treatment. She notes that Orserdu outperformed other hormone therapies, even in cases where the prior treatment duration was shorter.

Matro addressed the side effects of Orserdu, and the importance of understanding and managing them. She encourages patients, like Jane, to be informed about potential side effects and to have contact information for their clinic and nurse, in addition to a list of relevant medications on hand.

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