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Blood Test Provides Important Prognostic Information for Metastatic Triple Negative Breast Cancer Patients
Research by BCRF investigators shows that tumor DNA collected by liquid biopsy can identify patients at risk of poor outcome.
Using only a blood test, researchers have identified a biomarker that can predict prognosis in patients with metastatic triple negative breast cancer (mTNBC). The study, published in the Journal of Clinical Oncology, also identified unique genetic alterations in cancer-associated genes in mTNBC compared to primary TNBC (pTNBC).
Both the study’s findings and the method used to discover them are significant. Using a minimally invasive blood test, known as a liquid biopsy, scientists were able to analyze cell free DNA (cfDNA) to identify which mTNBC patients were at a high risk of dying from their disease. Cell-free DNA (cfDNA) is released into the blood by both normal and tumor cells. Liquid biopsy is essentially a sample of blood, from which cfDNA, circulating tumor cells, and other cellular components can be isolated and studied.
The study, was led by BCRF investigators Nancy Lin, Eric Winer and colleagues at Dana Farber Cancer Institute, Harvard Medical School, Massachusetts Institute of Technology, and Ohio State University. The researchers used stored blood from 164 patients enrolled in several clinical trials, as well as the EMBRACE metastatic cohort study to determine the fraction of tumor cfDNA (tumor fraction) and conducted genomic analyses of these samples.
What does this study mean for metastatic triple negative breast cancer patients?
Metastatic triple negative breast cancer remains one of the most difficult breast cancer subtypes to treat. Commenting on the impact of the findings, Dr. Nancy Lin notes that while it’s too early to use the latest findings in practice, they open the door to hopeful possibilities.
"This study paves the way for additional work to determine whether dynamic changes in cfDNA might provide a very early marker of response or lack of response to treatment, and guide treatment decisions in real time that could save or extend the lives of metastatic patients,” Lin says.
Another key discovery is the finding that using tumor cfDNA from liquid biopsies was just as accurate at identifying genetic alterations as a physical tumor biopsy, adding strength to the clinical utility of liquid biopsy.
“The study demonstrates the feasibility of studying tumor evolution over time using blood biopsies in metastatic breast cancer. The hope is that this will provide clues to drug resistance that can be exploited in future drug development,” Lin adds.
Summary of the key findings
- cfDNA represents a viable, accurate and minimally invasive alternative to tumor biopsy for genetic analysis. Tumor biopsy (either by needle or scalpel) is required to obtain tumor tissue for pathologic or genetic analysis. In metastatic cancer, tumor biopsy is often not practical due to accessibility or size of the tumor. Although biopsies are generally safe, they are an invasive procedure that can adversely affect the health of the patient, both physically and emotionally. Liquid biopsy has emerged as a promising alternative to tumor biopsies. There is considerable hope that clinical validation of liquid biopsy will provide a non-invasive means of real-time monitoring and even screening of breast cancer. The current study showed that using the tumor cfDNA from liquid biopsy was just as accurate at identifying genetic alterations as a physical biopsy.
- Tumor fraction of cfDNA was associated with poor outcomes. Tumor fraction, determined using a specialized algorithm, represents the proportion of cfDNA that could be attributed to the tumor. In this case, the tumor fraction is a surrogate, or biomarker of tumor size or presence. Only tumor fraction measurements of 3 percent or more are considered to be reliable tumor measurements based on the algorithm used. In this case, patients with high tumor fractions were those that measured at least 10 percent. The study showed that patients with a cfDNA tumor fraction greater than 10 percent had significantly shorter survival time than patients with tumor fractions less than 10 percent.
- mTNBC has specific genetic alterations that may provide clues to metastasis and drug resistance. Not all tumor genetic alterations occur as mutations in genes. In some cases, tumors will stop making certain genes–those that suppress tumor growth–while making more of the genes that promote tumor growth. Dr. Lin and her colleagues found that patients with a high tumor fraction were more likely to have extra copies of tumor promoting genes called NOTCH2, AKT2 and AKT3 than the original, primary tumor.
Triple negative breast cancer (TNBC) represents 10-15 percent of breast cancers and is an aggressive form of the disease with a high likelihood of becoming metastatic (spreading to new tissue). It is the most common type of breast cancer in people with mutations in the BRCA1 and BCRA2 genes and disproportionately affects women of African descent. Since TNBC lacks the known targetable markers estrogen/progesterone receptors and HER2, chemotherapy is currently the only treatment available for patients with TNBC.
Triple negative breast cancer research remains a priority at BCRF. In 2017 BCRF invested over $16 million in studies to understand TNBC, identify new potential drug targets and combinations treatment approaches, and to conduct clinical trials that are benefiting patients today.