Abstract 53P
Background
Older women (≥70yo) with ER+ breast cancer (BC), through shared decision making with their surgical and medical oncologists, are increasingly opting to forego upfront surgery in favor of primary endocrine therapy (ET). While the risk of BC-related mortality is ∼3% for these patients, progressive disease may occur in ∼20% of patients, indicating the importance of surveillance for tumor growth leading to local complications and potential inoperability. We assessed whether serial ctDNA testing can facilitate real-time treatment monitoring to inform on which patients may be safely treated with ET alone and which patients may need additional therapy.
Methods
This prospective observational study (NCT05914792) used a clinically-validated, personalized, tumor-informed multiplex PCR assay (SignateraTM) to monitor changes in ctDNA levels in pts on primary ET. Blood samples were collected every 3-6mo during follow up. Patient-reported outcomes (PROs) (NFBSI-16 and study-specific questions) were collected at each blood draw.
Results
We enrolled 36 patients to date (median age: 86 years, range: 75-94). Most patients (61%) had stage II/III BC and 22% had nodal involvement. Of 25 patients who had a pre-treatment draw, 36% were ctDNA+. All patients who cleared ctDNA by the second draw (median time to second draw: 6mo) had sustained responses to ET (stable disease or partial response), whereas patients who did not clear ctDNA all experienced tumor progression (progression-free interval, p < 0.0001). All 16 patients with pre-treatment ctDNA-negativity remained ctDNA- on subsequent blood draws. Over 90% of patients indicated that they were not anxious about their ctDNA results and the majority thought ctDNA testing helped inform their treatment plan.
Conclusions
This study enrolled older patients, in whom “right-sizing” surgery and systemic therapies is of paramount importance for optimizing outcomes and quality of life. Persistent ctDNA positivity was associated with progressive disease. Patients felt that ctDNA testing helped inform their care. Follow up will continue to 3-5 years; correlative studies involving caregiver reported outcomes, whole exome sequencing, and spatial gene and protein expression are ongoing.
Clinical trial identification
NCT05914792.
Legal entity responsible for the study
University of Pittsburgh IRB (21100091).
Funding
Shear Family Foundation, National Cancer Institute (NIH, USA).
Disclosure
T. Tin, C. Bridges, E. Kalashnikova, A.A. Rodriguez, M.C. Liu: Financial Interests, Personal, Full or part-time Employment, Employee at Natera with stock or option to own stock: Natera. All other authors have declared no conflicts of interest.