Feature

Blood test could predict risk for breast cancer recurrence

Peter Lee, MD
Peter P. Lee

Cytokine signaling responsiveness measured through a novel blood test may be a key determinant of intratumoral immunosuppressive potential and clinical outcome among patients with newly diagnosed breast cancer, according to study results published in Nature Immunology.

“This is the first success linking a solid tumor with blood biomarkers — an indicator of whether a patient will remain in remission,” Peter P. Lee, MD, chair of the department of immuno-oncology at City of Hope, said in a press release. “When patients are first diagnosed with cancer, it is important to identify those at higher risk for relapse for more aggressive treatments and monitoring. Staging and new tests based on genomic analysis of the tumor are currently available for risk stratification. A predictive blood test would be even more attractive but is not yet available. We are trying to change the status quo.”

Investigators pooled data on 40 patients with breast cancer followed for a median 4 years. They validated results in a separate cohort of 38 patients with breast cancer.

Results showed certain patients’ blood had altered signaling to two pro- and two anti-inflammatory cytokines in regulatory T cells. The researchers used these data to create a cytokine signaling index to allow for data to be processed through an algorithm that outputs a number to indicate future risk for disease recurrence.

HemOnc Today spoke with Lee about the need for a test such as this, how he and colleagues conducted the study, what they found, and what must be confirmed in future research.

Question: Why is a new test needed for this patient population?

Answer: After patients newly diagnosed with cancer undergo surgery with or without additional treatment, such as radiation or chemotherapy, they go into a period of waiting with a lot of anxiety and fear of their cancer coming back. There has always been significant interest in a test that could stratify patients at diagnosis. A few tumor tests are available, such as the diagnostic test Oncotype DX (Genomic Health), which estimates the likelihood for disease recurrence among patients with early-stage breast cancer. Based on the recurrence score, physicians can select patients who need to be monitored more carefully or treated more aggressively. There has not been an effective blood test like this.

Q: How did you conduct the study?

A: My group has been interested in studying the immune system of patients with breast cancer for a long time. During the past 10 years or so, we have been looking at its function. Immune cells are like soldiers in an army; they need to communicate constantly. Most of the communication occurs via secreted molecules, known as cytokines, and a lot of people measure these cytokines. We took it one step further and measured the cytokines as well as the ability of the receiving cell to respond to the cytokine.

Q: What did you find ?

A: We found that the signaling pattern is different among patients with breast cancer compared with healthy controls, but we found differences even within patients. Patients who went on to relapse had abnormal signaling patterns, whereas those who did not relapse had a relatively normal preserved signaling pattern compared with healthy controls. Based upon this knowledge, we applied the same test and thresholds to a validation cohort of patients with breast cancer to see if our findings held up, and they did. Additionally, the validation cohort perfectly predicted outcomes and confirmed our findings.

Q: What is next for research?

A: Although our results are exciting, in order for them to be applicable to patients in clinic going forward, we need to conduct a prospective study that includes more patients and follows them for a number of years. This would be a much larger study and would require more time and more funding that I am hoping we can receive support for.

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

A: Many research groups have measured cytokines, but what makes our study unique is that we measured the ability of immune cells to respond to cytokines. Some may ask how this blood test compares with circulating tumor DNA. We are measuring the host immune response, so we are looking at the other side of the equation. We are focused on the host immune system’s ability to prevent cancer cells from coming back. Potentially, because our test and circulating tumor DNA are looking at two different sides of the equation, these two tests could be combined for an even more specific prediction. – by Jennifer Southall

Reference:

Wang L, et al. Nat Immunol. 2019; doi:10.1038/s41590-019-0429-7.

For more information:

Peter P. Lee, MD , can be reached at City of Hope Comprehensive Cancer Center, 1500 Duarte Road, Duarte, CA 91010; email: plee@coh.org.

Disclosure: Lee reports no relevant financial disclosures.

Peter Lee, MD
Peter P. Lee

Cytokine signaling responsiveness measured through a novel blood test may be a key determinant of intratumoral immunosuppressive potential and clinical outcome among patients with newly diagnosed breast cancer, according to study results published in Nature Immunology.

“This is the first success linking a solid tumor with blood biomarkers — an indicator of whether a patient will remain in remission,” Peter P. Lee, MD, chair of the department of immuno-oncology at City of Hope, said in a press release. “When patients are first diagnosed with cancer, it is important to identify those at higher risk for relapse for more aggressive treatments and monitoring. Staging and new tests based on genomic analysis of the tumor are currently available for risk stratification. A predictive blood test would be even more attractive but is not yet available. We are trying to change the status quo.”

Investigators pooled data on 40 patients with breast cancer followed for a median 4 years. They validated results in a separate cohort of 38 patients with breast cancer.

Results showed certain patients’ blood had altered signaling to two pro- and two anti-inflammatory cytokines in regulatory T cells. The researchers used these data to create a cytokine signaling index to allow for data to be processed through an algorithm that outputs a number to indicate future risk for disease recurrence.

HemOnc Today spoke with Lee about the need for a test such as this, how he and colleagues conducted the study, what they found, and what must be confirmed in future research.

Question: Why is a new test needed for this patient population?

Answer: After patients newly diagnosed with cancer undergo surgery with or without additional treatment, such as radiation or chemotherapy, they go into a period of waiting with a lot of anxiety and fear of their cancer coming back. There has always been significant interest in a test that could stratify patients at diagnosis. A few tumor tests are available, such as the diagnostic test Oncotype DX (Genomic Health), which estimates the likelihood for disease recurrence among patients with early-stage breast cancer. Based on the recurrence score, physicians can select patients who need to be monitored more carefully or treated more aggressively. There has not been an effective blood test like this.

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Q: How did you conduct the study?

A: My group has been interested in studying the immune system of patients with breast cancer for a long time. During the past 10 years or so, we have been looking at its function. Immune cells are like soldiers in an army; they need to communicate constantly. Most of the communication occurs via secreted molecules, known as cytokines, and a lot of people measure these cytokines. We took it one step further and measured the cytokines as well as the ability of the receiving cell to respond to the cytokine.

Q: What did you find ?

A: We found that the signaling pattern is different among patients with breast cancer compared with healthy controls, but we found differences even within patients. Patients who went on to relapse had abnormal signaling patterns, whereas those who did not relapse had a relatively normal preserved signaling pattern compared with healthy controls. Based upon this knowledge, we applied the same test and thresholds to a validation cohort of patients with breast cancer to see if our findings held up, and they did. Additionally, the validation cohort perfectly predicted outcomes and confirmed our findings.

Q: What is next for research?

A: Although our results are exciting, in order for them to be applicable to patients in clinic going forward, we need to conduct a prospective study that includes more patients and follows them for a number of years. This would be a much larger study and would require more time and more funding that I am hoping we can receive support for.

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

A: Many research groups have measured cytokines, but what makes our study unique is that we measured the ability of immune cells to respond to cytokines. Some may ask how this blood test compares with circulating tumor DNA. We are measuring the host immune response, so we are looking at the other side of the equation. We are focused on the host immune system’s ability to prevent cancer cells from coming back. Potentially, because our test and circulating tumor DNA are looking at two different sides of the equation, these two tests could be combined for an even more specific prediction. – by Jennifer Southall

Reference:

Wang L, et al. Nat Immunol. 2019; doi:10.1038/s41590-019-0429-7.

For more information:

Peter P. Lee, MD , can be reached at City of Hope Comprehensive Cancer Center, 1500 Duarte Road, Duarte, CA 91010; email: plee@coh.org.

Disclosure: Lee reports no relevant financial disclosures.