Abstract discussant, Angela DeMichele, MD, MSCE, the Alan and Jill Miller Professor in Breast Cancer Excellence at the Perelman School of Medicine of the University of Pennsylvania, Philadelphia, complimented the study design and conduct of the ABC trial while exploring several possible explanations for the negative finding.
Angela DeMichele, MD, MSCE
“Investigators enrolled the right study population, given the underlying mechanism of action of the intervention, and patients received adequate study drug with minimal contamination,” said Dr. DeMichele. “Nonetheless, the trial was stopped early for futility. The direction and magnitude highly preclude the possibility that there would have been a benefit with more follow-up.”
According to Dr. DeMichele, given these results, aspirin should not be used to prevent breast cancer recurrence. Although it was not statistically significant, there is also the possibility that use of aspirin may increase breast cancer recurrence, she said. For those situations in which there are other options, decisions about the use of aspirin for other indications should include an individualized risk-benefit discussion between physicians and patients.
Although high levels of circulating inflammatory markers such as C-reactive protein and serum amyloid are associated with an increase in recurrence risk and a decrease in disease-free and overall survival in patients with hormone receptor–positive disease, Dr. DeMichele noted that targeting one component of inflammation alone may not be sufficient to prevent recurrence.
“Targeting one aspect of a very complex and redundant system is just not enough to reverse an effect,” she explained. “The translational studies from the ABC trial will be key to help us identify new approaches to trying to intervene in this situation.”
An Opportunity to Learn
According to Dr. DeMichele, clinicians will also learn from several ongoing, mechanistic window-of-opportunity trials of aspirin that are exploring various translational endpoints while combining aspirin with other agents such as checkpoint inhibitors.
“I think this study is very important to our field overall,” said Dr. DeMichele. “It underscores the need for prospective randomized trials that are essential to isolate the effects of interventions identified in observational studies.”
Finally, Dr. DeMichele emphasized the clinical value of negative trials. “Particularly when there has been meticulous biospecimen collection such as in the ABC trial, these analyses will be very helpful to us in gaining knowledge about the role of inflammation in recurrence and other interventions regardless of this trial’s outcome,” she concluded.
DISCLOSURE: Dr. DeMichele has received institutional research funding from Pfizer, Genentech, Calithera Biosciences, and Novartis.
