Liquid biopsy a ‘great option’ in metastatic breast cancer
Click Here to Manage Email Alerts
Liquid biopsy — once just a promising technology — is now an important tool for selecting treatment for certain patients with breast cancer, according to Melissa McShane, MD.
In the realm of cancer, liquid biopsy is an umbrella term that applies to the isolation and analysis of circulating tumor-derived material, such as DNA or whole cells, from bodily fluids — primarily blood.
Currently, most tests involve next-generation sequencing of cell-free DNA (cfDNA) that is released from tumor DNA for mutational analysis. McShane, assistant professor in the department of hematology/oncology and associate program director of the hematology/oncology fellowship program at Fox Chase Cancer Center and Temple University Health System, said this information, particularly in metastatic breast cancer, can pinpoint optimal therapeutic options for a patient.
Healio spoke with McShane to gain more insight into how liquid biopsy is currently being used in clinical practice, which patients benefit most from the technology and how physicians hope to use it in the future in breast cancer.
Identifying optimal treatment
Although researchers are studying other potential areas of use for liquid biopsy, its most common application in breast cancer is helping to identify appropriate targeted therapies based on mutational analysis, especially in patients with metastatic breast cancer who have exhausted other treatment options, according to McShane.
For example, testing for the PIK3CA mutation, which is present in approximately 40% of all HR-positive breast cancers, is particularly useful in determining the next line of treatment for patients with metastatic disease. In 2019, along with approval of alpelisib (Piqray, Novartis) for HR-positive, HER2-negative, PIK3CA-mutated breast cancer that progressed during or after an endocrine-based regimen, the FDA approved a companion diagnostic test, therascreen PIK3CA RGQ PCR Kit (Qiagen), to detect the PIK3CA mutation in a tissue and/or a liquid biopsy.
“Traditionally, we would perform next-generation sequencing on tissue, but there are patients with bone-only disease or in whom a tissue biopsy would be difficult to attempt,” McShane said. “In these situations, liquid biopsy has actually been able to detect the PIK3CA mutation and we are able to use this information to select next line of treatment with alpelisib.. Being able to determine next line of therapy with only a blood draw is a game changer.”
Liquid biopsy also appears beneficial for studying targeted therapies in metastatic breast cancer, according to McShane. Specifically there are patients who have previously undergone germline testing and are found to be BRCA1- and BRCA2-negative but are then found to have BRCA1 or BRCA2 somatic mutations on liquid biopsy or tissue next generation sequencing. Use of poly (ADP-ribose) polymerase inhibitors in these patients is now being studied in clinical trials.
Additionally, McShane noted that researchers are using this mutational analysis to connect patients who have run out of treatment options to trials in which they could potentially receive promising investigational therapies.
“If you have a patient who has limited standard-of-care therapy options left and they are found to have a particular mutation, like an FGFR mutation, and you have a clinical trial evaluating an FGFR inhibitor, it provides this patient with an additional treatment option. They may be able to receive more targeted, directed therapy based on their specific mutational profile, which we can potentially discover on liquid biopsy,” McShane said.
Furthermore, liquid biopsy has the potential to improve treatment in certain patients with advanced breast cancer regardless of mutational analysis, according to McShane.
“With regard to patients with triple-negative breast cancer, there can be less treatment options because they don’t have the option for hormone directed or HER2 directed therapy. For these patients, their PD-L1 status and their tumor mutational burden is extremely important, since this determines whether they can receive immunotherapy,” McShane said.
“It can provide a convenient way to discover more directed therapies for patients with metastatic breast cancer who have undergone all other treatment options.”
A noninvasive option
Liquid biopsy is certainly promising with respect to treatment for patients with metastatic breast cancer, but on a more basic level, the blood-based option represents a viable and attractive alternative to the standard, more invasive tissue biopsy, according to McShane.
For certain patients, such as those in whom attempting a tissue biopsy would be difficult, the blood draw offers a simple solution.
“All patients who are diagnosed with metastatic disease would benefit from a tumor mutational analysis or next-generation sequencing from tissue or blood,” McShane said. “Patients who are best suited for liquid options are those who have areas of disease where obtaining a biopsy would be difficult, patients who are a bit older and whom you may be nervous about putting through a biopsy, or patients who are just more resistant to undergoing a procedure. It’s also beneficial when there is a delay in being able to obtain a biopsy, such as during a COVID-19 surge.”
Insurers now also appear to be recognizing the value of liquid biopsy, with more widespread use accompanying a significant increase in coverage since Guardant Health released the first commercially available test in 2014, according to a study published in the JNCCN — Journal of the National Comprehensive Cancer Network in 2020. Specifically, in July 2019, more than one-third of 73 private payer policies included in the analysis provided coverage of liquid biopsy compared with none in 2016. The study also found that four Medicare Administrative Contractors issued final local coverage determination policies for circulating tumor DNA (ctDNA)-based panel tests for non-small cell lung cancer for Guardant360 (Guardant Health) in 2018 and InVisionFirst (Inviata) in 2019.
Importantly, McShane noted, many companies who manufacture these tests also allow a tissue biopsy after negative liquid biopsy results without additional charge to a patient’s insurance to ensure accurate analysis.
“That’s a nice feature as well because we can try the noninvasive route and if that gives us our answer, great, but we have a backup if the more invasive route is necessary,” McShane said.
Looking ahead
Currently, physicians primarily utilize liquid biopsy in the metastatic setting, but researchers are evaluating other ways in which it may be beneficial for patients with breast cancer.
Continual evaluation of a patient’s disease, for instance, is of particular interest, according to McShane.
“We are seeing improvements in OS of our breast cancer patients as the field evolves and new drugs become available. We know that tumors can mutate, so for our patients who are living longer, repeating studies to evaluate for acquisition of new mutations or development of new mutations or a change in receptor status is really important as well,” McShane said.
Additionally, serial monitoring of treatment response using liquid biopsy may also have potential.
“If we check a liquid biopsy before treatment and at the time of progression, are we able to detect changes that would help determine the best next step in treatment for a patient? That is the way the field is going and would be of most benefit, especially because liquid biopsies, as blood draws, make getting this information on the patient extremely accessible,” McShane told Healio.
One study, for example, published in JCO Precision Oncology in 2020, analyzed the clinical value of the presence and changes in ctDNA to predict tumor response and prognosis in patients with breast cancer treated with neoadjuvant chemotherapy. Results indicated that ctDNA taken after two cycles of neoadjuvant chemotherapy was predictive of local tumor response after all cycles and was associated with both DFS and OS, especially in patients with ER-negative breast cancer.
Additionally, researchers are evaluating the potential of the Guardant Reveal liquid biopsy to predict recurrence after treatment in a variety of cancers, including breast cancer, in the ORACLE study, according to a press release from Guardant Health. The prospective, multicenter, observational study includes 1,000 patients with early-stage cancer and will follow them until distant recurrence or up to 5 years.
The potential also exists for liquid biopsy to become more valuable in other types of breast cancer, such as HER2-positive disease, where it currently plays less of a role.
“In the realm of HER2-positive disease, there are not as many mutations that we would specifically be evaluating for at this time. However, as we explore and better understand the HER2 resistance mechanisms, liquid biopsy may actually play a bigger role in HER2-directed therapy, such as predicting why a patient may be losing a response to trastuzumab (Herceptin, Genentech) or pertuzumab (Perjeta, Genentech) and why they may respond better to tucatinib (Tukysa, Seagen), for example,” McShane said.
McShane noted, however, that uncertainty still persists around the utility of performing liquid biopsies in certain situations with respect to monitoring.
“The question, and burden, is are we just doing all of this for redundant information or is there a time at which it is most useful? There are times that we get these biopsies and they don’t tell us anything, meaning that a patient didn’t have any tumor mutations or there aren’t any directed therapy options. So, you’re stuck with the question later on: Should I repeat the test?” McShane said.
The research in this area is ongoing, and once physicians have answers to these questions, use of liquid biopsy is likely to increase even more, according to McShane.
Despite these lingering concerns, the technology is important and certainly beneficial for many patients. “All of our patients with metastatic breast cancer should be getting next-generation sequencing, and if testing tissue is not feasible, liquid biopsy provides a great option for patients. We should really be considering performing it upfront with a majority of our metastatic patients,” McShane said.
References
- Douglas MP, et al. J Natl Compr Canc Netw. 2020;doi:10.6004/jnccn.2020.7542.
- Guardant Health. Guardant Health initiates ORACLE study to evaluate performance of Guardant Reveal blood test to predict recurrence across early-stage cancers. https://investors.guardanthealth.com/press-releases/press-releases/2021/Guardant-Health-Initiates-ORACLE-Study-to-Evaluate-Performance-of-Guardant-Reveal-Blood-Test-to-Predict-Recurrence-Across-Early-Stage-Cancers/default.aspx. Published Oct. 5, 2021. Accessed March 16, 2022.
- Li S, et al. JCO Precis Oncol. 2020;doi:10.1200/PO.19.00292.
Collapse
Healio Interview
Click Here to Manage Email Alerts