Expert Highlights Promise of Liquid Biopsies in Breast Cancer

Joseph A. Sparano, MD

Joseph A. Sparano, MD

The role of liquid biopsies continues to evolve in the treatment of cancer. Invasive procedures, such as solid tumor biopsies, that can also be expensive and inconvenient, can be avoided with the use of liquid biopsies.

“A liquid biopsy panel could look for a range of different mutations that could tell you whether you are going to respond to drug A, B, C, or D, based on mutation A, B, C, and D,” said Joseph A. Sparano, MD.

However, liquid biopsies are still not being used as much as solid tumor biopsies in the field of breast cancer as they are in other areas such as lung cancer. This is due to the lack of effective treatments that require liquid biopsies. According to Sparano, this is likely to change as research continues to move forward.

In an interview withTargeted Oncology, Sparano, associate director for clinical research at the Albert Einstein Cancer Center, Montefiore Medical Center, discussed his presentation at the 2018 San Antonio Breast Cancer Symposium (SABCS) where he explained the current role of liquid biopsies in the breast cancer space and how this will evolve over time.

TARGETED ONCOLOGY:What is the current role of liquid biopsies in the breast cancer space?

Sparano:Right now, liquid biopsies are not being used as extensively in breast cancer as they are in other solid tumors, mainly because of the lack of clinical utility. That’s because we don’t really have many effective therapies that require that we do a liquid biopsy-type procedure in order to get the information that we need to make a decision, but I expect that with more time and with more discovery of novel targets, we will reach that point.

TARGETED ONCOLOGY:What advances have recently been made in this area of research?

Sparano:I think one of the most exciting developments this year at SABCS and one of the most practice-changing reports was the report of the KATHERINE trial in patients with HER2-positive locally advanced breast cancer who received neoadjuvant chemotherapy plus anti-HER2 therapy and had residual disease at the time of surgery. In that trial, patients were randomized to receive the immunoconjugate ado-trastuzumab emtansine (T-DM1; Kadcyla) versus standard trastuzumab (Herceptin). It was shown that the use of T-DM1 for a year was associated with about a 50% reduction in the risk of having a recurrence. The primary trial endpoint was met.

It was too early to evaluate the impact on survival, but there was a trend in the right direction. I think that’s a very encouraging finding. It has immediate impact on practice. It also indicates we might have reached a tipping point supporting the use of response to therapy, response to neoadjuvant therapy, chemotherapy, or chemo-immunotherapy, or a lack of response as a pharmacodynamic biomarker that can be used to identify patients likely to benefit from additional systemic therapy, adjuvant therapy given after neoadjuvant therapy. Now we have T-DM1 in HER2+ breast cancer, and we know from prior studies that capecitabine, for example, can also be effective in this setting in patients with residual triple-negative breast cancer (TNBC) after neoadjuvant therapy.

Again, I think we have reached a tipping point where we can now act on the information provided by response to therapy, which is a pharmacodynamic biomarker.

TARGETED ONCOLOGY:Are there any ongoing clinical trials evaluating the use of liquid biopsies in breast cancer?

Sparano:There are clinical trials ongoing in breast cancer evaluating the use of liquid biopsies, 1 being a trial being done in the UK for patients with TNBC, evaluating the role of pembrolizumab (Keytruda) in patients who are circulating tumor DNA—positive after local and systemic therapy. There are others ongoing, but that is one I think is the farthest along.

TARGETED ONCOLOGY:What are some existing challenges that need to be addressed?

Sparano:I think the clinical utility of these technologies could be improved by either a broader application of study and the identification of more effective therapies that are linked to a specific biomarker. I use the example of HER2 mutations and response to anti-HER2-directed therapies in a HER2-negative population, and that’s only 1 example. The problem is, we don’t have many examples of that, so I could envision in the future, a liquid biopsy panel could look for a range of different mutations that could tell you whether you are going to respond to drug A, B, C, or D, based on mutation A, B, C, and D. The greater the sum of those opportunities or alterations and therapies, the more likely the assay is going to be useful in directing patients to the right therapy.

The other major application would be in surveillance of patients who are at high risk of recurrence, then using that biomarker to direct an intervention or direct a therapy to see if it can prevent the development of metastasis. The FDA has now recognized metastasis-free survival as a regulatory endpoint that could support the approval of a drug.

TARGETED ONCOLOGY:Where do you hope this research goes in the next 5 to 10 years?

Sparano:I hope to see in the future we may be able to rely more on liquid biopsy procedures to replace, to the extent possible, solid tumor biopsies, which can be invasive, associated with complications, [and are] expensive and inconvenient. I think that really represents a very promising application of this technology.

TARGETED ONCOLOGY:Is there anything else you would like to highlight from your talk?

Sparano:The main takeaway point is the promise of these technologies in breast cancer. We haven’t leveraged these technologies nearly as well as some of our colleagues in other disciplines, especially in the field of lung cancer, but I think we are just at the cusp of being able to do something with that. I do think there is potential to greatly transform how we manage early and advanced stage breast cancer in the next 5 to 10 years.