Liquid biopsies are being described as revolutionary for their promises for the future treatment of breast cancer.
Tissue Biopsy Problems
Currently, a surgical tissue biopsy remains the gold standard. However, there are several problems with a tissue biopsy.
It’s challenging to get a biopsy from some areas of the body, like the lungs.
The turnaround of biopsy results can take about ten days and sometimes more.
Cancer cells continue to change their shape as long as they’re functioning, which means a tissue biopsy is only a snapshot in time.
By the time chemotherapy is given, that tumor probably requires new analysis.
Only one biopsy is given per patient.
This means as much as 1 in 5 patients receive the wrong medication.
As much as 70 per cent of BC are found by the patient and not by a biopsy.
Tissue biopsies are also expensive.
The principle behind a liquid biopsy is based on the presence of a tumor shedding bits of itself that float into the blood stream.
The tumor shedding leaves one organ, let’s say the breast, and enters the bloodstream to find another organ normally, the lymph nodes, bones, liver, lungs and brain.
A liquid biopsy is a simple and non-invasive alternative to surgical biopsies which enables doctors to discover a range of information about a tumour through a simple blood sample. Traces of the cancer’s DNA in the blood can give clues about which treatments are most likely to work for that patient.
So, if you receive a negative result, your doctor will likely order a tissue biopsy to confirm that the results are correct. According to an article published in April 2020 in Cure, some studies have shown the sensitivity of liquid biopsies range from 60 percent to 85 percent
There are three ways in which tumor shedding occurs.
Circulating Tumor Cells (CTC): CTCs are cancer cells that split away from a tumor and circulate in the bloodstream. They can sometimes exit the bloodstream and enter other organs, growing into new, metastatic tumors. This tumor shedding in the blood can be measured to determine if a patient has cancer. The more shedding found in the blood, the higher the likelihood of the patient having late-stage cancer. As a result, CTC-based tests can have lower specificity in early-stage settings.
Circulating Tumor DNA (ctDNA): ctDNA is DNA that circulates in the bloodstream and derives from cancerous cells and tumors. As tumors grow, cancerous cells die and are replaced by new ones. The dead cells get broken down, and their contents, including DNA. These are released into the bloodstream. Like CTCs, ctDNA can be measured in a patient sample to determine if a patient has cancer. ctDNA is known for its higher sensitivity relative to alternative biomarkers.
Exosomes:Exosomes are extracellular vesicles.
What’s a vesicle?
Vesicles are tiny sacs that transport material within or outside the cell.
Exosomes are responsible for cell-to-cell communication and the transmission of diseases. Exosomes are particularly useful as a basis for liquid biopsy, as they are secreted (as in discharged) by living cells rather than by dead ones. As a result, exosome-based assays offer a more comprehensive real-time window into the patient’s health and have higher sensitivity. They also provide logistical benefits because exosomes are highly stable and easy to obtain and distinguish.
Why is this a good thing?
In oncology, the liquid sample is analyzed specifically to find mutations for cancer.
An examination of these bits of tumor floating around in the blood stream potentially provides for more information than a tissue biopsy does. It is particularly helpful for metastatic cancer because it can tell us where the cancer is going. It means LB could help us to stay one step ahead of cancer growth. Baring in mind 90 per cent of BC patients die of metastatic BC this could indeed be revolutionary.
The whole treatment journey could be personalized.
Overall sensitivity for the test was 51.5%, with a steady improvement in detection across cancer stages:
17% at stage I,
40% at stage II,
77% at stage III, and
90% at stage IV
“Cancer is not a static disease. As the disease progresses, molecular characteristics change over time, and these changes are important to understand how the disease responds to treatment as well as how resistance develops,”
“That makes it really important for a clinician to have real-time access to these metrics.”
With a simple blood test
Liquid biopsies provide the possibility of a quicker and more accurate early-stage cancer detection across a wider range of cancer types.
Using current standards like surgical tissue biopsy, only about 25% of cancers are detected via screening. The remaining 75% are detected when the patient is symptomatic and from a black perspective, normally in later stages.
This is, at least in part, why BC has become the number 1 cancer impacting women across the world.
Plus, liquid biopsies could well be beneficial for detecting cancers that currently do not have proven screening methods, so they currently require invasive tissue biopsies.
Advantages of Liquid Biopsy
Liquid biopsies utilize genetic sequencing for many purposes in oncology.
It’s quicker to do and cheaper with a shorter turnaround. A biopsy of metastatic sites costs around $16,000, and Angle (a liquid biopsy company), in their trials, so for research purposes, said the single-use test costs around $100.
Tissue biopsies take about ten days and more. LB promises to be much quicker than this.
Often it was difficult to get enough information from the surgical biopsy and really depended upon the area of the body.
Tissue biopsy could not typically capture the genomic landscape of the entire tumor.
Now more information can be taken from fewer cells.
LB is safer and more convenient
LB can be repeated as is needed without harm.
LB can also be taken via saliva, urine and the spinal tap.
Research has sequenced sections of DNA and found markers associated with types of cancer, such as the protein HER2 in breast cancer (Shtivelman).
Another area where liquid biopsies excel is when a tumor has metastasized, meaning it has spread to multiple sites in the body (Parnell). It is not practical or often possible to collect tissue from each tumor for analysis. Thus, liquid biopsies are more advantageous for providing an overview of the mutations present in each of the tumor sites or when tumors are in an unreachable area where tissue cannot be collected in the traditional way.
More than anything, if you have the DNA sequence of your tumor to match with pharmaceutical medication, a new level of personalized treatment emerges. This explains why it is set to be a billion-dollar industry.
Disadvantages of Liquid Biopsy
A lot is still not known.
Sensitivity is not reliable in the stages below stage 4 cancer:
17% at stage I,
40% at stage II,
77% at stage III, and
90% at stage IV
The Food and Drug Administration (FDA) has expanded the approved uses for a blood test, which can help doctors pick the best treatments for some people with cancer but not all.
LB is complementary to TB and not a replacement.
TB remains the gold standard so-called because the quality of the tissue subject to examination is better for it is solid tissue.
There is better sensitivity for assessing amplification in TB than liquid biopsy
Tissue biopsies are fully utilized when a known tumor’s location is confirmed and available for extraction.
Liquid biopsies are at best limited to being used for screening, identifying mutations in metastatic cancer, and tracking changes in mutations for treatment
The sample may not represent mutations that actually are present in a tumor.
Tissue biopsies are irreplaceable in identifying the nature of tumors.
According to the company Biochain
Research demonstrates that neither biopsy method is capable of sampling an entire tumor and revealing complete details of all present mutations. This is a setback for both diagnosis and treatment, which tend to be based on the mutations.
In general practice, this would determine precision treatment by drugs, but only 9 out of 36 recommended drugs were concordant, or 25%. Another similar study tracking specific genetic mutations found consistent results in only 17% of cases (Chae, et al.) Oncotarget, Vol. 7, No. 40, 2016
At the moment, liquid and tissue biopsies function as two distinct tests with different methods and functions. Using both biopsy methods may prove to be costly and time-consuming. More research and advancement are necessary to conclusively select a superior biopsy.
When deciding which biopsy to use, the most likely deciding factor is which phase of the process a patient is in: screening, diagnosis, treatment, remission, or relapse. From there, the best decision can be made.
Thermography has greater sensitivity as a breast screening tool.