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Let's Talk Metastatic Breast Cancer: What Does the Future Hold?

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Published on December 29, 2020

Exciting Advances in Metastatic Breast Cancer Treatment

Metastatic breast cancer research is in an exciting phase with multiple forthcoming treatments. Yet the question remains: What do these advances mean for patients living with metastatic disease? In this final installment of "Let’s Talk Metastatic Breast Cancer,” immunotherapy specialist Dr. Andreopoulou, MD, of Weill-Cornell Medicine shares information on the exciting frontiers of research, new clinical trials and the future of MBC treatment. Follow along as we look forward to 2021 and beyond. 

This program is sponsored by Seattle Genetics. This organization has no editorial control. It is produced by Patient Power, and Patient Power is solely responsible for program content.


Transcript | Let's Talk Metastatic Breast Cancer: What Does the Future Hold?

How is Metastatic Breast Cancer Treatment Changing?

Dr. Andreopoulou: What really has changed recently is a shift in the mindset of how we address the disease, realizing that the disease is not static, there is a dynamic evolution, so it is our focus to capture the disease, get a snapshot at each point of its clinical evolution, and target any changes at any point of disease progression accordingly.

This is what we basically perceive as precision medicine, and this is where technology is, liquid biopsy comes to provide us with the most appropriate tools. Imagine, it is not really possible obtaining biopsies from our patients at every single point when the disease is progressing to get information in order to optimize treatment care and match the disease biology with what is the best available therapy. So liquid biopsies are now revolutionizing this area, optimizing treatment in that aspect.

As... I have to admit and say that sequencing of treatment in metastatic setting remains still controversial. We do have in our basket a number of cytotoxic treatments, but still, there are some biologic treatments approved, but there are so many other treatments in clinical development. So, having a real-time picture of the disease status at each point enables medical oncologists, especially in academic settings, to channel our patients in appropriate clinical studies that match the disease biology. And I think that's a new opportunity.

What is A Liquid Biopsy?

It's basically a simple blood test where at the lab, we're looking to detect circulating tumor cells or elements of the tumor cells that will basically be proof of the concept of disseminated disease. It is an easier way to detect. There are data on circulated tumor cells and other biologic elements of cancer cells. It just not established as yet as a robust indicator of metastatic disease.

Notably, data from our laboratories at Weill Cornell Medicine have been demonstrating the importance of epigenetics as a key regulator in breast cancer progression. So, this pre-clinical data show that pharmacologic or genetic inhibition of the catalyst EZH2 is important to prevent invasion and metastases and gives a new opportunity for bringing a new biologic treatment into the clinical testing. Data from our laboratories at Weill Cornell demonstrate that the pharmacologic or genetic inhibition of the catalyst EZH2 impairs the process of distant metastases, proving that epigenetics is a key player in the progress of breast cancer.

Recurrent metastatic disease might go undetected for a considerable time. Always, of course, reflecting the biology of the disease. That brings the question to us clinicians, and we're always challenged in the clinic when we see patients on follow up who were treated previously for early-stage breast cancer, and there is no clinical evidence of disease. We're always challenged with the question, is there anything we can do to detect breast cancer recurrence before our patients come to us with symptoms? So, this is a very exciting area of investigation.

What Does the Future Hold for Metastatic Breast Cancer Patients?

Again, technology is our major ally here, providing us more recently with tools as circulating tumor cells, or the exosomes, or DNA as potential indicators of recurrent metastatic disease. And this is very important because intervening earlier, we do have better chances of addressing the disease, even in a metastatic setting, on more of a curative intent. And again, the disease is dynamic and is evolving, and this gives us a wider spectrum to intervene and interact further invasion, further metastases. And optimize conditions to treat breast cancer as a chronic disease. So, we're investing a lot. These are very early stages to draw firm conclusions that we do have a way beyond conventional imaging or routine blood work that we do to detect the disease early, but I think that these initial steps will lead to tools that will allow us to detect the disease at very early points.

Metformin is an anti-diabetic drug, extensively used with millions of prescriptions every year. Retrospective data suggests effectiveness in breast cancer medicine with optimization of outcomes. Data from the neoadjuvant setting are supporting of Metformin in terms of reducing the risk of breast cancer. That's huge, especially for diabetic patients. For non-diabetic patients, the role of Metformin remains to be addressed. It is a proof-of-principles since sugars are promoting growth of cancer cells, and we also know that insulin acts as a growth factor. So, there is a rationale to support the use of Metformin.

The M32 study is going to give us the main answer to this question for the integration of Metformin since Metformin is combined with what is the standard of care therapy, which is the endocrine therapy. And here, another point that I want to make is that the aromatase inhibitors might be inducing diabetes. So, the role of Metformin, it's not only to reduce the risk of breast cancer through direct effect on the sugar control, diabetes control, and insulin metabolism but also indirectly... Referring to the induced hyperglycemias, and also indirectly by controlling the effect of the standard anti-endocrine therapies in the glucose metabolism.

So, in terms of the hunger hormone ghrelin and unacylated ghrelin, there are pre-clinical data, [inaudible] data that are suggesting that even low doses of unacylated ghrelin, they stop tumor growth across different tumor types. And it remains now to bring this to clinical testing with a clinical study, where we will translate what we see in the laboratory into the clinic. There is a major focus for developing an investigator-initiated study, again exploring here a new avenue of what metabolism is as a player in the complex process of the orchestra of the cancer disease. 

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