Testing for Tumor Mutations: Liquid Biopsy Versus Traditional Biopsy


Liquid biopsies, virtually unknown even a year or two ago, are becoming common tools in precision diagnostics for cancer. Here, I will try to explain some of the more important differences between liquid and “traditional” tumor biopsies.

Biopsies of solid tumors (e.g., lung, breast, or brain tumors) involve surgically removing a small part of a tumor and sending it to pathology lab. In the last few years, doctors have also started to send some tumor samples to special service labs that analyze tumor DNA for the presence of cancer-related mutations.

By definition, regular biopsies can be intrusive and are sometimes associated with side effects, such as bleeding or infection. However, they provide some really essential information; i.e., the histology and grade of the tumor and other tumor characteristics necessary to determine the best choice of treatment. For lung cancer, for example, a biopsy determines the type of tumor—adenocarcinoma, squamous cancer, small-cell lung cancer, or another, less common type. For breast cancer, a routine test will determine if the tumor expresses estrogen, progesterone receptors, and a protein called HER2. These tests are critically important in guiding treatment choices. If mutational analysis of cancer-related genes is also performed (which doesn’t always happen, unfortunately), it may guide treatment with targeted drugs. Continue reading…


One Patient, Two Cancer DNA Tests, Two Different Results

Excerpt:

“A couple years ago, Sibel Blau, an oncologist outside of Seattle, was working with the company Guardant Health to test their novel ‘liquid biopsies’ in patients. The idea behind liquid biopsies is both elegant and promising. A doctor takes a blood sample from a patient, and then Guardant looks for tumor DNA floating in the blood, allowing doctors to identify the tumor’s unique mutations and offer a personalized drug regimen—all without an invasive tissue biopsy. Blau was excited to be on board.

“When that study wrapped up, Blau still had Guardant test kits left over, so she offered some to her patients at no cost to them. At this point, Blau was routinely ordering DNA sequencing of traditional tissue biopsies, so some patients got both tests. The tissue DNA test from Foundation Medicine was “routine” in her practice, but even that test had only become available in 2012. The field of cancer DNA has been changing fast.”

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If you’re wondering whether this story applies to your own cancer case or a loved one’s, we invite you to use our ASK Cancer Commons service.


Liquid Biopsies for Identification of EGFR Mutations and Prediction of Recurrence

Excerpt:

“Three manuscripts published in the recent issue of the Journal of Thoracic Oncology, the official journal of the International Association for the Study of Lung Cancer (IASLC), explored the versatility of liquid biopsies by identifying EGFR mutations using circulating tumor DNA (ctDNA) in urine and plasma and examining circulating tumor cells (CTCs) in plasma to predict the risk of lung cancer recurrence after surgical resection. Collectively, these findings illustrate the potential and reach of liquid biopsies in both identifying patients suitable for targeted treatment as well as predicting cancer recurrence.

“Lung cancer is the most common type of cancer with the highest cancer-related mortality worldwide. Non-small cell lung cancer (NSCLC) accounts for roughly 85% of lung cancer and most patients present with advanced disease at diagnosis. Surgical resection is the preferred treatment option for patients with medically operable tumors. However, disease recurrence occurs in approximately 50% of cases. Patients with advanced disease are often not candidates for surgical resection and commonly harbor driver mutations that can be targeted by drugs. A major challenge for assessing driver mutations, such as epidermal growth factor receptor (EGFR) mutations, in advanced disease is the scarcity of suitable biopsy tissue for molecular testing. A minimally invasive alternative to invasive tissue biopsy is the use of liquid biopsy, which analyzes ctDNA or CTCs in a liquid biological sample (i.e. urine, blood, or serum).”

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Do you have questions about this story? Let us know in a comment below. If you’re wondering whether this story applies to your own cancer case or a loved one’s, we invite you to use our Ask Cancer Commons service.


Blood Test Gives Early Warning of Melanoma Relapse

“A blood test can detect changes in tumor DNA, potentially helping doctors detect melanoma relapse far earlier, according to a study in England.

“Scientists at Cancer Research UK found the blood test detects mutations in circulating tumor DNA indicating potential drug resistance or relapse, which would allow treatment to start earlier and increase the chance for a patient’s survival.

“Although the study was small, and scientists say the test’s accuracy needs to be tested in a much larger trial before it is used in clinics, any possibility of improving how cancer is tracked will improve treatment.”


Case for Testing Cancer in Blood Builds, One Study at a Time

“Two new studies published on Wednesday of patients with breast and prostate cancers add to growing evidence that detecting bits of cancer DNA circulating in the blood can guide patient treatment.

“Enthusiasm is building for ‘liquid biopsies,’ which offer a non-invasive alternative to standard tissue biopsies and are expected to be a multibillion-dollar market.

“But a key question remains: Do they really work?

“The stakes are high. At least 38 companies are working on liquid biopsies for cancer, according to analysts at investment bank PiperJaffray, who think the U.S. market alone could eventually reach $29 billion a year.”


A Blood Test for Early Detection of Breast Cancer Metastasis

“The chances of being cured of breast cancer have increased in recent decades, however if the tumour has metastasised, the disease remains essentially incurable. One reason for this could be that the metastases are detected late, after they have grown enough to cause symptoms or be seen on a radiological scan. If they could be found sooner, it might be possible to treat the new tumours. Research findings from Lund University in Sweden now provide new hope for a way of detecting metastases significantly earlier than is currently possible.

“The discovery was made by a research team led by Lao Saal, M.D. Ph.D, and is based on what is known as cell-free circulating DNA – small fragments of genetic material from different cells which circulate in the blood. It is normal to have low amounts of such DNA material in the blood, but in the case of diseases such as cancer, these amounts can increase. Furthermore, in cancer patients, the circulating DNA contains the genetic mutations which are specific to the tumor.

“Lao Saal and his colleagues used previously gathered material from a breast cancer study which has been underway in Lund since 2002. The material contained samples from surgically removed tumours from patients with non-metastatic disease as well as blood samples taken from the patients at regular intervals during the years in which they were followed up.”


New Blood Tests, Liquid Biopsies, May Transform Cancer Care

“A new type of blood test is starting to transform cancer treatment, sparing some patients the surgical and needle biopsies long needed to guide their care.

“The tests, called liquid biopsies, capture cancer cells or DNA that tumors shed into the blood, instead of taking tissue from the tumor itself. A lot is still unknown about the value of these tests, but many doctors think they are a big advance that could make personalized medicine possible for far more people.

“They give the first noninvasive way to repeatedly sample a cancer so doctors can profile its genes, target drugs to mutations, tell quickly whether treatment is working, and adjust it as the cancer evolves.

“Two years ago, these tests were rarely used except in research. Now, several are sold, more than a dozen are in development, and some doctors are using them in routine care.”


DNA Blood Test Detects Lung Cancer Mutations

“Cancer DNA circulating in the bloodstream of lung cancer patients can provide doctors with vital mutation information that can help optimise treatment when tumour tissue is not available, an international group of researchers has reported at the European Lung Cancer Conference (ELCC) in Geneva, Switzerland.

“The results have important implications for the use of cancer therapies that target specific cancer mutations, explains Dr Martin Reck from the Department of Thoracic Oncology at Lung Clinic Grosshansdorf, Germany, who presented the findings at the conference.

“Testing for the presence of these mutations in the tumour itself is not always possible, however studies have suggested that DNA from the tumour that circulates in the bloodstream of patients may provide similar information.

“The large international ASSESS study aimed to compare the ability of blood testing to detect EGFR mutations with the more standard method of testing the tumour itself.

” ‘We were really asking a question on behalf of patients,’ Reck said: ‘Is there a valid test that can identify an EGFR mutation and give me the opportunity for superior treatment, even if my lung tumour is not accessible for bronchoscopy or CT-guided biopsy? And, are the results of this blood test in agreement with the results of the “gold-standard” tissue test?’ “


A Blood-Based Test for EGFR Mutations in NSCLC Is Being Developed

“Clovis Oncology is evaluating a blood-based assay to detect EGFR mutations in circulating tumor DNA in non-small cell lung cancer patients as a way to better identify candidates for treatment with rociletinib (CO-1686), its investigational EGFR inhibitor, a Clovis scientist said this week.

“During a talk at the Cambridge Healthtech Institute Molecular Medicine Tri-Conference held here, Chris Karlovich, principal scientist for molecular diagnostics at Clovis, said that his company is comparing the performance of Sysmex Inostics’ BEAMing assay service to that of Qiagen’s TheraScreen EGFR PCR test in a subset of patients from the company’s “third-generation inhibitor of mutant EGFR lung cancer” (TIGER) clinical trial for rociletinib.

“The goal, Karlovich said, is to overcome some of the limitations of tissue-based PCR testing in identifying EGFR mutations, particularly the T790M resistance mutation, which can be used to identify patients who have become resistant to EGFR-directed therapy and thus are candidates for second- or later-line treatment with rociletinib. In addition, Karlovich said, blood-based assays like BEAMing could potentially be used to more easily monitor response to the drug.

“Rociletinib was designed to selectively target initial activating EGFR mutations and the T790M resistance mutation, while sparing wild-type EGFR at anticipated therapeutic doses, with an improved toxicity profile, according to Clovis’ website.”