In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 103-103
Abstract:
103 Background: Hormone receptor–positive breast cancer (HR+ BC) is the most common cause of BC-related death. Over half of metastatic recurrences occur ≥ 5 years (y) from diagnosis. Detection of minimal residual disease (MRD) via circulating tumor DNA (ctDNA) can identify cancer recurrence months to years in advance and may be an important tool to guide therapy. Little is known about ctDNA in the late adjuvant setting. We investigated ctDNA dynamics and clinical outcomes in pts ≥ 5 y from diagnosis of high-risk early-stage HR+ BC. Methods: Patients with high-risk HR+ BC (T3-4 or N2-3 or T1 with 3+ lymph nodes, or T2N1 [and Oncotype RS ≥ 26; grade 3; or Ki-67 ≥ 20%]) with no evidence of recurrence 5 y after diagnosis were prospectively identified and consented. Plasma samples were collected at time of consent and at routine visits every 6-12 mos. Whole-exome sequencing (WES) was performed on primary tumor tissue to identify somatic mutations and design for each patient a RaDaR assay, a tumor-informed liquid biopsy test to detect plasma ctDNA. Per current practice standards, pts did not undergo regular surveillance imaging. All pts were followed for development of local and/or distant metastatic recurrence, as determined by their clinical provider. Results: Of 103 pts enrolled, 85 had sufficient tumor tissue, and 83 pts had successful WES. Personalized RaDaR assays were designed targeting 12-51 variants (median, 36), and used to test 219 plasma samples from 83 pts. The number of plasma samples per patient ranged from 1-7 (median, 2). 57 pts (68.7%) had stage 3 disease, and most (75, 90.4%) received curative-intent chemotherapy. All pts received endocrine therapy (ET). 39 (47%) remained on adjuvant ET at time of last follow up. Of 44 pts who completed adjuvant ET, 41 (93.2%) received 〉 5 y of treatment. Time from diagnosis to first sample ranged from 4.9-20 y (median, 8.4 y). Median (range) follow up was 10.2 (6.7-22.3) y from diagnosis and 1.8 (0-3.6) y from first sample. 5 pts (6%) developed distant metastatic recurrence and 2 pts (2.4%) had locoregional recurrence. 4/83 (5%) pts were MRD+ at study entry and 8/83 (10%) pts were MRD+ at any time point. 5/5 (100%) pts with metastatic recurrence were MRD+, with ctDNA lead times up to 37.6 mos. ctDNA was detected at tumor fractions of 0.0027-26.84% (median, 0.396%). 2/8 (25%) MRD+ pts had not had clinical recurrence at latest follow up, one with no follow up since detection and one 15.4 mos from ctDNA detection (with ctDNA levels 0.045% and 26.84%). Conclusions: Here we report—to our knowledge—the first data on ctDNA detection in late adjuvant HR+ BC. 10% of pts had MRD at ≥ 5 y from diagnosis. ctDNA analysis identified MRD in all cases of distant recurrence. ctDNA was detected in 2 pts who have not yet experienced recurrence. Longer follow up is necessary for these pts at high risk. Additional studies will determine if ctDNA-guided intervention can alter clinical outcomes.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2022.40.16_suppl.103
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2022
detail.hit.zdb_id:
2005181-5