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Biomarkers and Metastatic Breast Cancer

Now that you’ve gotten an overview of biomarkers (link 101) and how they are used in the diagnosis and treatment of breast cancer, we are going to dive into what this means in the context of metastatic breast cancer (MBC). YSC was lucky to bring together Dr. Reshma Mahtani and patient advocate Dr. Yolanda Jameau to discuss how biomarker testing can inform the field of MBC and what is coming up next.

As a refresher, what is biomarker testing?

For those of you new to the subject, biomarkers are defined as “a characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention, including therapeutic interventions,” according to the National Institutes of Health (NIH) Biomarker Working Group. Essentially, they are molecules that indicate either abnormal or normal body processes, which gives more information on how the specific breast cancer type should be treated. Biomarkers can be found in tumor tissue, blood tests or saliva, depending on the marker being looked at.

How is biomarker testing used in the diagnosis of breast cancer?

In breast cancer, the “big 3” biomarkers and those most commonly tested are: estrogen-receptor (ER), progesterone-receptor (PR) and the overamplification of the HER2 gene. The presence of these factors can be both prognostic (e.g. HER2+ breast cancer can be more aggressive, but there are targeted therapies available, like trastuzumab) as well as predictive (e.g. research shows how ER/PR+ breast cancer will likely respond well to hormonal therapy, like tamoxifen).

How is biomarker testing used in the diagnosis of metastatic breast cancer?

When a patient receives a diagnosis of metastatic breast cancer, their tumor is tested for expression of estrogen and progesterone receptors, as well as for overexpression of the HER2 protein. Even in cases of breast cancer recurrence, these biomarkers should be tested, since the characteristics of the tumor can change from the original breast cancer. The standard of care is first to confirm the metastatic diagnosis by biopsy (with assessment of ER/PR/HER2 status) and to figure out where the cancer has spread in the body with radiographic imaging. It is important to confirm these factors, so that the treatment is personalized to the current diagnosis.

Perhaps one of the subtypes where there has been the most progress with the use of a biomarker-directed treatment is HER2 positive breast cancer, which accounts for about 20% of all breast cancers. When first identified, HER2 positive breast cancer was felt to be one of the most aggressive subtypes and had poorer outcomes. This has changed dramatically with the introduction of several HER2 targeted therapies. Currently, there are eight different drugs available for HER2+ MBC and this has led to dramatic improvements in outcomes for these patients. Having more personalized choices, especially for patients living with MBC who may switch treatments multiple times, not only gives a more personalized experience, but reduces side effects like those that occur with ongoing chemotherapy.

There are new treatments in the MBC setting that can also be tailored to certain biomarkers. For example, in triple negative metastatic breast cancer, chemotherapy used to be the only treatment option. Now, if the PDL1 protein is overexpressed in the tumor and immune cells, the medical oncologist may suggest immunotherapy in combination with chemotherapy to help the immune system best recognize and fight those cancer cells.

Another example of a biomarker that can inform treatment decisions is the presence of a PIK3CA gene mutation, which is found in approximately 40% of ER+/HER2- breast cancer. Once this mutation is detected, a patient with ER+/HER2- metastatic breast cancer is a candidate for alpelisib (e.g. Piqray), which is an approved treatment given with hormonal therapy. This combination has been shown to prolong the time it takes for the cancer to progress compared to hormonal therapy alone.

What are some recent developments in biomarker testing and metastatic breast cancer?

The advancements in the field of biomarker testing have greatly benefited those diagnosed with early-stage and metastatic breast cancer. Research in precision oncology continues and shows great promise. There are more and more clinical trials looking at gene mutations and the possibility that other cancer drugs can be used in the breast cancer setting.

One of the most exciting developments is the increased ability to use circulating tumor DNA (ctDNA) testing. This is a blood test that can be used in patients with MBC and is very sensitive in picking up DNA fragments from cancer cells. If mutations in the tumor are evaluated using this technology, it can eliminate more invasive procedures like tumor biopsies. The hope is that this technology may also be used to monitor for recurrence in early stage patients.

We hope that you learned more about the field of biomarkers and how it’s impacting the future of metastatic breast cancer treatment. You can find other information on this topic through YSC’s Biomarker Series (link to main page) and explore YSC’s MBC education and support services.