Novel blood assay has potential to detect, predict breast cancer spread

Researchers at Christiana Care Health System’s Helen F. Graham Cancer Center and Research Institute and scientists from Genomic Profiling LLC developed a new blood assay that they believe could significantly improve the ability to detect breast cancer and predict whether the cancer has the potential to spread.

“This simple blood test, used in combination with mammography, can be a transformative tool in the fight against breast cancer,” Jennifer Sims-Mourtada, PhD, director of translational breast cancer research at Center for Translational Cancer Research at Graham Cancer Center, who developed the test along with scientists from Genome Profiling LLC (GenPro), said in a press release. “Using this test could minimize overdiagnosis and treatment while potentially providing significant savings in health care-related costs. Studies have shown that mammograms alone are not optimal for diagnosing all types of breast cancer.”

The novel assay differs from others in that it focuses on identifying an epigenetic biomarker within circulating blood cells’ DNA that are part of the body’s immune system.

Jennifer Sims-Mourtada, PhD, director of translational breast cancer research at Helen F. Graham Cancer Center & Research Institute, and Adam Marsh, PhD, cofounder of Genome Profiling LLC, developed an assay designed to detect breast cancer and predict whether it has the potential to spread.

Christiana Care and GenPro have filed a provisional patent application with the U.S. Patent and Trademark Office as the first step in the process toward clinical trials as well as FDA approval for this novel blood-screening assay.

“Right now, there is no truly effective method for routine monitoring of patients to follow in response to treatment for breast cancer and for possible recurrence of cancer,” Sims-Mourtada said in the release. “Using the assay we have developed, in conjunction with routine monitoring, enables us to follow changes in the immune response to detect an increase in tumor cells over time. This test can allow for much earlier detection of recurrence or metastatic disease before it is visible with standard imaging and enable much earlier treatment.”

HemOnc Today spoke with Sims-Mourtada about how this assay was developed, whether it has the potential to truly distinguish between invasive breast cancers and those that may never spread or pose a threat, and the need for an effective tool that can do just that.

 

Question: How was the assay discovered?

Answer: I am an immunologist by training and, within the past couple of decades, we have learned a lot about interactions with the immune system and cancer. We know cancer changes the immune system and we can see different stages of how the immune cells react to a cancer. I wanted to see if we could use this to follow the stage of a cancer. We know that one way that cancers can affect the immune system is what we call epigenetic modification — modification that changes the DNA so that different genes are expressed in the immune cells. I wanted to see if we could follow these changes to see if a cancer is early enough where the immune system is capable of controlling the cancer or if it is a later-stage cancer where it has modified the immune system so that it cannot attack or get rid of it — the stage where we see that cancers become invasive. To do this, I collaborated with Adam Marsh, PhD, who owns the start-up company Genome Profiling LLC. He developed a sensitive way to look at all populations of cells that have changes in their epigenetic profiles within the context of much larger populations. We were able to use his algorithm to identify changes in the blood of women with invasive cancers vs. those who do not have any cancer. This work was initially funded by a grant from the state of Delaware, which gave us the seed money to conduct our initial studies.

Q: What exactly does the test do?

A: This test is designed to be a companion to mammography to provide physicians with more information about potential breast lesions. The goal is to predict which lesions are likely to be or become invasive so patients can receive proper treatment, whereas those who have lesions that show a more benign pattern can be spared the physical, economic and psychological costs of biopsy and treatment. Because this is a blood-based test, patients that do not show an invasive pattern can be followed longitudinally with repeated tests to monitor for any changes that may signal progression from benign to invasive disease.

 

Q: Can you provide a preliminary sense for how efficacious the test is?

A: We are at the very early stage of research. We just recently sent in our second cohort validation study and we were able to stratify women who have no evidence of cancer, women who have ductal carcinoma in situ stage 0 noninvasive breast cancer and those who have invasive breast cancer with high significance (P = .0001). We have also completed our first blinded cohort where we are seeing about 70% to 75% accuracy, which is excellent at this stage with our small sample size of about 75 patients. We feel that to have this degree of accuracy with such a small subset is truly very promising.

 

Q: Does the test have the potential to truly distinguish between invasive breast cancers and those that may never spread or pose a threat?

A: Based upon our preliminary data, it does look very promising. To improve this, we will have to conduct longitudinal studies where we can see if we are able to detect someone with an early-stage cancer that has the potential to progress. We are looking into piggybacking on some other clinical trials where they are providing different treatments to women with early-stage breast cancers. One treatment involves surgical resection without any further treatment. By piggybacking on these trials, we hope we will be able to pick out the women who will progress with these types of cancers. Right now, our data are very exciting.

 

Q: What is the timeline for how this will move forward?

A: We are at the early stages and have just completed our first study. What we want to do next is develop a plate-based assay that is relatively inexpensive and standardized so we can test it in multicenter trials. This will be our clinical test. We are looking for collaborators and funding that will allow us to conduct large-scale clinical trials. Because this is going to be a companion diagnostic, meaning we will use this assay in combination with mammography, patients will still receive standard of care. This makes our regulatory burden a lot less than what it would be for some of the other diagnostics. We are hoping to get to market in about 5 years and have everything fully approved.

 

Q: Can you talk a bout the balance between enthusiasm for this assay’s potential and the realism that research is in the beginning stages?

A: We need to conduct a lot of testing to validate these initial findings, which is the case with any research study. Research takes a long time, especially when dealing with a diagnostic that could potentially affect every woman in the world. We want to make sure we get it right. This is why we need to conduct large-scale studies to truly show that this blood test is capable of detecting invasive cancer and not only to use as a screening tool, but also to follow women once they have had the cancer to see if there is cancer recurrence.

 

Q: Is there anything else that you would like to mention?

A: Since we have started mammographic screening back in the 1990s, we have detected many early-stage breast cancers. The question has always been whether these will progress to invasive cancers and affect the survival of women. We know that only between 30% and 50% of stage 0 breast cancers will ever progress. Yet we do not know specifically which ones will progress, so we treat everyone the same. This is estimated to be about $4 billion per year in health care costs for women who receive treatment but do not need it. Hopefully this assay will allow us to differentiate which cancers truly need treatment, and there will be a huge health care cost savings and a psychological savings cost where we can pick out those cancers that will not amount to anything. – by Jennifer Southall

 

For more information:

Jennifer Sims-Mourtada, PhD, can be reached at Christiana Care Health System, 4755 Ogletown Stanton Road, Newark, DE 19718; email: jsimsmourtada@christianacare.org.

Disclosure: Sims-Mourtada reports no relevant financial disclosures.

Researchers at Christiana Care Health System’s Helen F. Graham Cancer Center and Research Institute and scientists from Genomic Profiling LLC developed a new blood assay that they believe could significantly improve the ability to detect breast cancer and predict whether the cancer has the potential to spread.

“This simple blood test, used in combination with mammography, can be a transformative tool in the fight against breast cancer,” Jennifer Sims-Mourtada, PhD, director of translational breast cancer research at Center for Translational Cancer Research at Graham Cancer Center, who developed the test along with scientists from Genome Profiling LLC (GenPro), said in a press release. “Using this test could minimize overdiagnosis and treatment while potentially providing significant savings in health care-related costs. Studies have shown that mammograms alone are not optimal for diagnosing all types of breast cancer.”

The novel assay differs from others in that it focuses on identifying an epigenetic biomarker within circulating blood cells’ DNA that are part of the body’s immune system.

Jennifer Sims-Mourtada, PhD, director of translational breast cancer research at Helen F. Graham Cancer Center & Research Institute, and Adam Marsh, PhD, cofounder of Genome Profiling LLC, developed an assay designed to detect breast cancer and predict whether it has the potential to spread.

Christiana Care and GenPro have filed a provisional patent application with the U.S. Patent and Trademark Office as the first step in the process toward clinical trials as well as FDA approval for this novel blood-screening assay.

“Right now, there is no truly effective method for routine monitoring of patients to follow in response to treatment for breast cancer and for possible recurrence of cancer,” Sims-Mourtada said in the release. “Using the assay we have developed, in conjunction with routine monitoring, enables us to follow changes in the immune response to detect an increase in tumor cells over time. This test can allow for much earlier detection of recurrence or metastatic disease before it is visible with standard imaging and enable much earlier treatment.”

HemOnc Today spoke with Sims-Mourtada about how this assay was developed, whether it has the potential to truly distinguish between invasive breast cancers and those that may never spread or pose a threat, and the need for an effective tool that can do just that.

 

Question: How was the assay discovered?

Answer: I am an immunologist by training and, within the past couple of decades, we have learned a lot about interactions with the immune system and cancer. We know cancer changes the immune system and we can see different stages of how the immune cells react to a cancer. I wanted to see if we could use this to follow the stage of a cancer. We know that one way that cancers can affect the immune system is what we call epigenetic modification — modification that changes the DNA so that different genes are expressed in the immune cells. I wanted to see if we could follow these changes to see if a cancer is early enough where the immune system is capable of controlling the cancer or if it is a later-stage cancer where it has modified the immune system so that it cannot attack or get rid of it — the stage where we see that cancers become invasive. To do this, I collaborated with Adam Marsh, PhD, who owns the start-up company Genome Profiling LLC. He developed a sensitive way to look at all populations of cells that have changes in their epigenetic profiles within the context of much larger populations. We were able to use his algorithm to identify changes in the blood of women with invasive cancers vs. those who do not have any cancer. This work was initially funded by a grant from the state of Delaware, which gave us the seed money to conduct our initial studies.

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Q: What exactly does the test do?

A: This test is designed to be a companion to mammography to provide physicians with more information about potential breast lesions. The goal is to predict which lesions are likely to be or become invasive so patients can receive proper treatment, whereas those who have lesions that show a more benign pattern can be spared the physical, economic and psychological costs of biopsy and treatment. Because this is a blood-based test, patients that do not show an invasive pattern can be followed longitudinally with repeated tests to monitor for any changes that may signal progression from benign to invasive disease.

 

Q: Can you provide a preliminary sense for how efficacious the test is?

A: We are at the very early stage of research. We just recently sent in our second cohort validation study and we were able to stratify women who have no evidence of cancer, women who have ductal carcinoma in situ stage 0 noninvasive breast cancer and those who have invasive breast cancer with high significance (P = .0001). We have also completed our first blinded cohort where we are seeing about 70% to 75% accuracy, which is excellent at this stage with our small sample size of about 75 patients. We feel that to have this degree of accuracy with such a small subset is truly very promising.

 

Q: Does the test have the potential to truly distinguish between invasive breast cancers and those that may never spread or pose a threat?

A: Based upon our preliminary data, it does look very promising. To improve this, we will have to conduct longitudinal studies where we can see if we are able to detect someone with an early-stage cancer that has the potential to progress. We are looking into piggybacking on some other clinical trials where they are providing different treatments to women with early-stage breast cancers. One treatment involves surgical resection without any further treatment. By piggybacking on these trials, we hope we will be able to pick out the women who will progress with these types of cancers. Right now, our data are very exciting.

 

Q: What is the timeline for how this will move forward?

A: We are at the early stages and have just completed our first study. What we want to do next is develop a plate-based assay that is relatively inexpensive and standardized so we can test it in multicenter trials. This will be our clinical test. We are looking for collaborators and funding that will allow us to conduct large-scale clinical trials. Because this is going to be a companion diagnostic, meaning we will use this assay in combination with mammography, patients will still receive standard of care. This makes our regulatory burden a lot less than what it would be for some of the other diagnostics. We are hoping to get to market in about 5 years and have everything fully approved.

 

Q: Can you talk a bout the balance between enthusiasm for this assay’s potential and the realism that research is in the beginning stages?

A: We need to conduct a lot of testing to validate these initial findings, which is the case with any research study. Research takes a long time, especially when dealing with a diagnostic that could potentially affect every woman in the world. We want to make sure we get it right. This is why we need to conduct large-scale studies to truly show that this blood test is capable of detecting invasive cancer and not only to use as a screening tool, but also to follow women once they have had the cancer to see if there is cancer recurrence.

 

Q: Is there anything else that you would like to mention?

A: Since we have started mammographic screening back in the 1990s, we have detected many early-stage breast cancers. The question has always been whether these will progress to invasive cancers and affect the survival of women. We know that only between 30% and 50% of stage 0 breast cancers will ever progress. Yet we do not know specifically which ones will progress, so we treat everyone the same. This is estimated to be about $4 billion per year in health care costs for women who receive treatment but do not need it. Hopefully this assay will allow us to differentiate which cancers truly need treatment, and there will be a huge health care cost savings and a psychological savings cost where we can pick out those cancers that will not amount to anything. – by Jennifer Southall

 

For more information:

Jennifer Sims-Mourtada, PhD, can be reached at Christiana Care Health System, 4755 Ogletown Stanton Road, Newark, DE 19718; email: jsimsmourtada@christianacare.org.

Disclosure: Sims-Mourtada reports no relevant financial disclosures.