This kind of testing can also use next-generation sequencing to computer-analyze hundreds of genes and show if a cancer has developed gene mutations that could help it resist certain drugs. “The only way to know that is through molecular testing, yet it’s underutilized,” Dr. Teplinsky says. “Reasons include cost and insurance complexity, clinician and workflow barriers, limited awareness among patients—health literacy plays a role—and structural inequities that leave minority, older, and low-income patients tested least.”
Molecular testing can be done at the time of an initial biopsy, later using tissue from that same biopsy or another biopsy, or via a blood test called a liquid biopsy. “I would urge people with metastatic breast cancer to make sure they’re periodically asking questions like, ‘Have I had molecular testing, and do we need to repeat it? Do I need a liquid biopsy, and when would be the right time for me to do that?’” says Dr. Teplinsky.
Novel Endocrine Therapies
About four out of five breast cancers are hormone-receptor positive (HR+), meaning that the hormones estrogen and/or progesterone help fuel their growth. Initial treatment usually centers around hormone therapy—treatments that starve the cancer of the hormones it needs to grow. “Generally we give a class of medications called aromatase inhibitors, which block estrogen production,” Dr. Teplinsky says. However, as many as 36% of people in ongoing treatment for HR+ metastatic breast cancer eventually develop an ESR1 gene mutation that makes cancer cells resistant to certain drugs. This means the aromatase inhibitors may ultimately stop working. That’s one reason researchers are focused on finding different ways to treat hormone receptor-positive breast cancer, with breakthroughs happening in an area known as novel endocrine therapies.
The most noteworthy of these developments is the introduction of oral SERDs (selective estrogen receptor degraders). “Instead of blocking actual estrogen, SERDs block and degrade the estrogen receptors [on cancer cells],” Dr. Teplinsky explains. “If estrogen’s floating around and there’s no receptor for it to attach to, the cancer cell dies because there’s no way for the ‘food’ to enter it.” While an older SERD called fulvestrant was available as a monthly intramuscular injection, the new oral SERDs elacestrant and imlunestrant come in convenient pill form, and more SERDs and other novel endocrine therapies are in the pipeline. Often, oral SERDs are paired with targeted therapies like CDK4/6 inhibitors to enhance efficacy. “We now have more options for hormone receptor-positive breast cancer when our first-line or second-line treatment options don’t work,” Dr. Teplinsky says. “It allows us to stay in that hormone-blocking treatment phase rather than moving to chemotherapy.”
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