Biomarkers May Guide Next Steps of Metastatic Breast Cancer Treatment

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If metastatic breast cancer no longer responds to a given therapy, finding out what targetable mutations a patient has may guide the next steps for treatment, an expert said.

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Metastatic breast cancer may become challenging to manage over time, highlighting the need for adaptive treatment strategies that integrate results from biomarker testing as the cancer develops resistance to therapies, an expert said.

Dr. Rebecca Shatsky, associate clinical professor of medicine and co-leader of the breast disease team at University of California San Diego, discussed what happens after a patient’s breast cancer no longer responds to initial hormone therapy, during a session of CURE® Educated Patient® Updates in Metastatic Breast Cancer.

It becomes important for cancer teams to monitor progression through imaging techniques such as CT scans, positron emission tomography (PET) scans and MRIs, she noted. Metastatic breast cancer can manifest in various ways, including new tumor growth and complications like fluid buildup in the lungs or abdomen, making timely detection crucial. Another modality used to make next treatment decisions is biomarker testing.

"When your hormone therapy stops working, we go and we get that biomarker testing again,” Shatsky said. “So basically, after your first breast cancer treatment stops working, … the guidelines now recommend that (your doctor should) do a liquid biopsy or (a circulating tumor) DNA test to look for specific mutations that are targetable, so those being ESR1."

A disease’s response to a given treatment is individualized in nature, and the time to progression (the time from diagnosis or the start of treatment until the disease worsens or spreads to other parts of the body) varies for each patient. Shatsky made an analogy between cancer resistance and bacteria developing resistance to antibiotics, emphasizing the importance of biomarker testing to identify new treatment possibilities.

"These are some of the things that we're looking for on that liquid biopsy when you have estrogen positive, HER2-negative breast cancer, and these are mutations that can happen in cancer genes,” Shatsky explained. “(These include the) PI3 kinase mutation, (which) we mentioned because the drug alpelisib (Piqray) targets the PI3 kinase alpha receptor."

There are other specific mutations, including ESR1, PI3 kinase and AKT, all of which may play a role in breast cancer cell growth and resistance. Shatsky noted the complexity of estrogen positive, HER2 negative-breast cancer and the diverse mutations that may occur.

"(Data are) saying 50% of people will develop ESR1 mutations,” Shatsky said. “Some data say 40%, some says 50%. … If you have the ESR1 mutation, then you're more likely to have a response from (Piqray) based on the clinical trials they did, so the FDA (Food and Drug Administration) has restricted that to patients that cancer does have that mutation."

Skatsky noted that Truqap (capivasertib) is another promising drug in this space. It has not yet been approved by the FDA, and the potential timeline for its approval is uncertain, Shatsky added. Clinical trials have demonstrated potential efficacy with Truqap in patients who have progressed on CDK4/6 inhibitors.

"When you have experienced progression on your CDK4/6 inhibitor, we can look for that PI3 kinase mutation,” Shatsky said. “And your doctor may have already done that before progression as well. You can do all of that testing at the time of diagnosis and at the (time of) progression. It doesn't have to be one or the other."

ESR1 mutations have been shown to be associated with resistance to hormonal therapies. Shatsky explained that these mutations often develop in response to aromatase inhibitors. Thus, it is important to test for ESR1 mutations before starting a new treatment, as it can provide context for personalized therapeutic approaches.

"If your cancer has (ESR1 mutations), compared to someone whose cancer does not, it means that it is a bit more resistant to those hormonal therapies and it can be associated with a little bit more rapid cell growth," she explained.

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