the Research Project

The development of a blood test to predict if breast cancer will return

WE NEED BETTER AND MORE ROBUST SCREENING STRATEGIES TO PREDICT WHICH WOMEN WILL DEVELOP METASTATIC RECURRENCE

When breast cancer returns and spreads to other parts of the body, most commonly to the bones, liver, lung and/or brain, it is called metastatic breast cancer (MBC) or stage 4 breast cancer.

An estimated 20% to 30% of women diagnosed with early stage breast cancer will have a recurrence at a distant site in the body. 

We need better ways of predicting which women are at high risk of MBC.

The Details

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GREATER THAN 90% OF DEATHS DUE TO BREAST CANCER ARE A CONSEQUENCE OF METASTASIS

There is no cure for MBC and nearly all women will eventually die from it. One of the overarching problems is that we still do not know how to definitively predict who will develop metastatic recurrence and how to prevent it for any individual woman.

THERE ARE NO TESTS AT THE END OF THERAPY TO INDICATE WHETHER A PATIENT IS CURED OR WILL HAVE A METASTATIC RECURRENCE

At the end of therapy, there is no way to determine whether all the cancer has been completely eradicated from the body or whether it will spread to other parts of the body. That means there is no test to determine whether a patient has been cured of her breast cancer and whether or not it will return.

Tests like Mammaprint or Oncotype DX provide a recurrence risk score for certain women with breast cancer. However, those tests rely on breast tissue at the time of diagnosis.

Using current risk stratification criteria, there are patients deemed high-risk who do very well with standard therapy and never experience a recurrence and some patients with low-risk profiles who still die of breast cancer. There also remains a risk of recurrence in high-risk patients even after treating them with the most effective chemotherapy agents.

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WE NEED SENSITIVE AND AFFORDABLE SCREENING STRATEGIES TO IDENTIFY PATIENTS AT HIGH-RISK OF DEVELOPING LETHAL MBC BEFORE IT OCCURS.

We need novel tests for early stage breast cancer that can measure risk of metastatic recurrence at the end of therapy when tissue is no longer available.

Dr. Salhia’s lab is working on developing a blood test to determine which women with early stage breast cancer are at high-risk of developing metastatic recurrence at the end of a patient’s treatment when no tissue remains. They published their initial results in 2015 and have since been funded by the National Cancer Institute at the National Institute of Health to work on this study.

Tumors shed DNA into the blood stream. This type of DNA is known as circulating or cell-free DNA because it has been released from the inside of cells. Modern science can now identify both genetic and epigenetic tumor alterations in cell-free DNA. A blood test that can measure tumor-associated changes in cell-free DNA is also known as a liquid biopsy.

Dr. Salhia’s lab is specifically interested in developing a liquid biopsy that can measure tumor-associated DNA methylation. DNA methylation is an epigenetic modification and is the addition of a methyl chemical group to DNA, which has profound effects on gene expression.

Epigenetics (literally means “on top” of DNA) is the study of how chemical modifications to DNA and associated proteins can alter gene function without involving changes in DNA sequence.  

However, since the methyl chemical groups are tightly bound to DNA they can also serve as useful biomarkers. Biomarkers are biological markers which are measurable substances in an organism used to indicate a disease process, outcome, or therapeutic response. 

The DNA methylation liquid biopsy we are developing is intended to detect residual disease at the end of therapy. It is essentially a way to look for the needle in the haystack.  Residual disease has the potential to spread to other parts of the body and form a distant metastasis.  Identifying residual disease before it spreads can help lead to measures for preventing recurrence. 

If you are an eligible blood donor for this study we will use your sample to research if our DNA methylation liquid biopsy can detect residual disease and predict recurrence. The liquid biopsy will be called the CpG4C™ test.

IMPROVING TREATMENT STRATEGY AND PREVENTING RECURRENCE

Our research study is of major significance as it seeks to build upon a roadmap to improving treatment strategy as well as preventing metastatic recurrence in all subtypes of breast cancer for all women of all races.

We propose to validate a liquid biopsy as a prognostic marker of distant recurrence in the pre-metastatic setting following definitive therapy. In addition, this test can be developed as an end of therapy (surgical and medical) predictive biomarker for patients who could benefit from surgery after neoadjuvant therapy, and/or additional chemotherapy and surveillance.

Such a marker is a major advance and would serve as an adjunct to existing molecular tests such as Mammaprint and Oncotype DX.

HOW OUR STUDY COULD END BREAST CANCER

The expectation is that a liquid biopsy for recurrence will reduce breast cancer mortality by better distinguishing indolent from aggressive disease using a sensitive method to detect microscopic cells that still remain after the completion of aggressive and definitive therapy.

Furthermore, if we could segment the breast cancer population into low and high-risk groups, then screening individuals more routinely might lead to more cost-effective therapies, potentially produce fewer unnecessary interventions, and result in more aggressive and prophylactic treatments for those identified to be at high risk. 

This study will undoubtedly improve upon our current understanding of breast cancer and could potentially lead us towards novel therapeutic targets and prevention methods. 

Our study design, sample resources, expertise in breast oncology, together with our technical capabilities and know-how is expected to lead to a clinical test within the next 5 years. Our study will increase the likelihood of long-term progression-free survival for breast cancer patients world-wide.

We Need Your Help to
End Breast Cancer

We aim to prove we can eliminate breast cancer by improving the treatment strategy and prevent recurrence in all subtypes of breast cancer. You can be a part of the solution. We need blood samples from women who have stage IV breast cancer or from women who have completed therapy and have early stage breast cancer

We cannot beat breast cancer without you! By taking the survey and supporting our research, you are making a difference in countless lives.