Researchers have discovered that it may be possible to detect and treat dormant tumor cells in breast cancer survivors, according to new findings presented by DeMichele et al at the European Society for Medical Oncology (ESMO) Congress 2023 (Abstract 244MO). The results may have offered a proof-of-concept for the strategy of preventing breast cancer recurrence.
Background
Although breast cancer survival rates continue to improve as a result of advances in detection and treatment, when the disease recurs, it is incurable. Currently, there is no way to predict which patients are most likely to experience breast cancer recurrence, and for the 30% of patients who relapse, continuous and indefinite treatment is the only option for attempting to slow the cancer’s growth.
“Recurrence is a lifelong issue and problem for breast cancer survivors because it can happen decades after their initial treatment,” explained senior study author Angela DeMichele, MD, MSCE, FASCO, the Alan and Jill Miller Professor in Breast Cancer Excellence and Co-Director of the 2-PREVENT Breast Cancer Translational Center of Excellence at the Abramson Cancer Center at the University of Pennsylvania.
Angela DeMichele, MD, MSCE, FASCO
After breast cancer treatment, dormant tumor cells—also referred to as measurable residual disease—may survive and reactive years or decades later in some patients. Once the cells begin to expand and circulate in the bloodstream, they can cause the spread of metastatic breast cancer. Patients who have measurable residual disease may be more likely to experience breast cancer recurrence and decreased overall survival.
“The dormant/latency phase is an opportune window to intervene because we’ve found that these dormant cells are sensitive to drugs that don’t work against actively growing cancer cells,” revealed co–study author Lewis Chodosh, MD, PhD, Chair of Cancer Biology and Co-Director of the 2-PREVENT Breast Cancer Translational Center of Excellence at the Abramson Cancer Center at the University of Pennsylvania. “Contrary to current thinking, drugs that are not effective against metastatic disease may be highly effective when used during the dormant phase of disease,” he added.
Study Methods and Results
In the phase II CLEVER study (ClinicalTrials.gov identifier NCT03032406)—results of which were presented at the ESMO Congress 2023—the researchers examined the efficacy of several U.S. Food and Drug Administration–approved drugs in patients who were previously treated for breast cancer and found to have measurable residual disease despite being otherwise considered cancer-free. All of the breast cancer survivors involved in the study completed their cancer treatment within the 5 years prior to study enrollment, and nearly 50% of them had triple-negative breast cancer—which historically has a 30% rate of recurrence within 5 years.
The researchers demonstrated that they were able to successfully clear dormant tumor cells from over 80% of the patients across all three study arms.
After a follow-up of 4 years, the researchers discovered that none of the breast cancer survivors had cancer recurrence. To date, only 3.9% (n = 2/51) of the patients have experienced breast cancer recurrence.
In a previous study—published by Abravanel et al in The Journal of Clinical Investigation—the researchers identified the pathways that may allow dormant tumor cells to survive for decades and showed in preclinical studies that drugs targeting those pathways could eliminate dormant tumor cells.
Next Steps
Researchers at the Perelman School of Medicine and Abramson Cancer Center at the University of Pennsylvania recently received a $10 million grant from the Department of Defense to find and target dormant tumor cells prior to breast cancer recurrence.
The researchers expect the grant funding to support the continued monitoring of more than 200 patients who enrolled in the CLEVER study as well as in three separate studies. They also hope to develop a more sensitive test for dormant tumor cells, identify the optimal testing strategy for measurable residual disease, determine the long-term benefits of the study treatments, and uncover how dormant cancer cells may evade the immune system. The researchers will use patient-reported outcome surveys to better understand the patients’ perspectives on this type of active surveillance approach—including the psychological and emotional ramifications for breast cancer survivors.
“This grant will allow us to extend the research we’ve already started and continue to answer questions about what happens to [patients] years down the line. We want to get away from ‘watchful waiting’ and move toward ‘active surveillance’ by learning how we can intervene to prevent relapse of breast cancer,” Dr. DeMichele highlighted.
Two additional clinical trials are currently ongoing to confirm and extend the results of the CLEVER study: the phase II ABBY trial (NCT04523857) and the phase II PALAVY trial (NCT04841148).
“We have a lot more work to do to prove that this approach can prevent breast cancer recurrence, but these results are encouraging and show that it’s feasible to safely detect and therapeutically target dormant disseminated tumor cells,” underscored Dr. DeMichele. “With the help of this grant funding, we want to be able to get to a point where we can effectively test patients for dormant cells after treatment and either reassure them that they’re likely cured, because they don’t have dormant [tumor] cells, or if they do have [the] cells, provide them with an effective treatment to stop their cancer from returning,” she concluded.
Disclosure: For full disclosures of the study authors, visit cslide.ctimeetingtech.com/esmo2023.
