Biomarkers Guide Treatment for Metastatic Breast Cancer

Understanding the biomarkers present in metastatic breast cancer can help patients and their care teams make educated decisions on treatment options, an expert said.

Dr. Shannon Puhalla discussed different aspects about metastatic breast cancer including biomarkers, treatment options and advice for patients at the CURE® Educated Patient® Updates in Metastatic Breast Cancer event in Pittsburgh.

Puhalla, who moderated the in-person event, is an oncologist at the UPMC Hillman Cancer Center at UPMC Magee-Womens Hospital in Pittsburgh, senior associate medical director of oncology at the National Surgical Adjuvant Breast and Bowel Project and assistant professor of medicine at University of Pittsburgh.

The discussion primarily focused on ER-positive, HER2-negative metastatic breast cancer, “one of our most common types of metastatic breast cancer,” Puhalla said in an interview with CURE.

She explained that metastatic breast cancer, also known as stage 4 disease, is a disease that spreads via the bloodstream to other places beyond the breast and local axillary lymph nodes. The most common locations for metastasis include the liver, lungs, brain and bones, although this can occur anywhere outside of the breast or local axillary lymph nodes.

Puhalla mentioned that during the event, she presented a slide on the progress made in this space regarding treatment, especially in the past 40 years.

“From 1970 to 2010 … so 40 years, basically, there were three new drugs for ER-positive metastatic disease,” Puhalla told CURE. “But in the time since 2010 up until the present, there’s been 10 new drugs. So, to see that pace of progress — and we’ve seen it in the clinic — but I think to see that highlighted as that timeline really brought home how we’ve made such progress particularly in this group of patients through research.”

She attributed the drug development process for the advancements made in metastatic breast cancer treatment over the past 10 years, which placed a specific emphasis on genomic targeted therapy such as PIK3CA, ESR1 and a new group of patients considered HER2-low.

“[It’s] not just lumping ER-positive, HER2-negative [disease], but also including these other genomic predictors and targeted therapies,” Puhalla said.

Identifying Biomarkers in Metastatic Breast Cancer

Puhalla noted that there are several biomarkers in metastatic breast cancer that can not only classify the disease but also identify targets for treatment. Originally, biomarkers were thought of as estrogen receptor, progesterone receptor and HER2.

“These are biomarkers that we've had now for 20 years in terms of our classifications,” Puhalla explained. “But basically, this helps us to know what type of breast cancer in particular.”

Genomic targets are mutations present in tumor DNA that can be used as targets for treatment. These are assessed either through tissue-based testing via tumor samples or blood-based testing, which are also known as liquid biopsies.

Tumors and their microenvironment (the cells, molecules and structures that support and surround a tumor cell) can change over time, highlighting the importance of liquid biopsies to analyze tumors over time.

“[The target] definitely can change over time,” Puhalla said. “And I think that’s something that we’ve seen particularly with the ESR mutation story, that is a treatment-emergent mutations that absolutely changes over time. So definitely if you have other mutations, like PIK3CA, which are more driver mutations, typically you either have it from the beginning (at diagnosis) or you don’t.”

Available Treatment Options and Sequencing

Even with an “explosion of new therapies” for ER-positive, HER2-negative metastatic breast cancer, as Puhalla described it, the question arises of the best sequence to give these therapies.

Hormone therapy is typically considered first-line therapy for patients with ER-positive, HER2-negative metastatic breast cancer, Puhalla explained, although there are some data that demonstrate that this can also be given as second-line therapy with endocrine therapy in the first-line setting.

There are several options for treatment beyond the first-line setting, Puhalla said.

“Whether we're looking at someone who, say, for instance, has a BRCA gene mutation, maybe you're going to look at PARP inhibitors,” Puhalla explained. “[For] someone who has a PIK3CA mutation, you may be looking at medicines like capivasertib (Truqap) or alpelisib (Piqray). If someone has an ESR mutation, maybe looking at elacestrant (Orserdu).”

Other options may include second-line CDK4/6 inhibitors for patients whose disease progressed on first-line therapy, she added.

Puhalla concluded that not only is it important to understand the available treatment options, but also to know that certain therapies can either preclude or encourage other options down the line.

“With metastatic disease, it's a balance between treatment efficacy and quality of life, and really trying to understand how someone can best optimize their quality of life, No. 1, by keeping their cancer in control, but also No. 2, by looking at the different side effects,” she said. “And maybe you have three or four different options in the second line, but maybe one option has [fewer] side effects, or [with] one option, you may not lose your hair. So there's different things that really help to determine [what is best for the patient], especially when you have relatively equal options in subsequent lines of therapy.”

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