Abstract P2-01-05: Impact of post-treatment ctDNA and residual cancer burden (RCB) on outcomes in patients with triple-negative breast cancer (TNBC) and residual disease
Authors: Priyanka Sharma, Shane R Stecklein, Bruce F Kimler, Rachel Yoder, Kelsey Schwensen, Joshua M Staley, Qamar J Khan, Anne P O'Dea, Lauren E Nye, Manana Elia, Jaimie Heldstab, Trisha Home, Stephen Hyter, Kamilla Isakova, Harsh B Pathak, Andrew K Godwin
Journal: Cancer Research (2022)

Abstract Introduction: Residual disease (RD) after neoadjuvant chemotherapy (NACT) is associated with high risk of recurrence in TNBC. RCB classification is prognostic in patients with RD. Recent studies show that post-NACT circulating cell-free tumor DNA (ctDNA) also provides prognostic information in patients with RD. Most TNBC patients with RD receive adjuvant therapy after surgery (chemotherapy and/or radiation), thus ctDNA status at completion of all adjuvant therapy (end of treatment, EOT) may be a better indicator of long-term prognosis. Furthermore, the impact of EOT ctDNA status on prognosis in context of RCB is of interest. Utilizing data from a prospective registry, the objective of this study was to investigate the impact of EOT ctDNA status and RCB class on outcomes in TNBC patients with RD. We hypothesized that RCB and EOT ctDNA status may provide complementary prognostic information. Methods: Study population included TNBC patients with RD post-NACT and available EOT plasma samples who were enrolled in an IRB-approved multisite prospective registry between 2011 and 2018. EOT samples were collected after completion (1-6 months) of all curative treatment (local and systemic). ctDNA was isolated and subjected to next generation sequencing (QIAseq 275-gene Human Comprehensive Cancer Panel on an Illumina NextSeq 550). Samples demonstrating pathogenic/likely pathogenic variant(s) with 3-40% allelic frequencies were considered ctDNA positive. Variants with allelic frequencies ≥40% were included in ctDNA positive status only if not present in ClinVar8/dbSNP9 as a known germline variant. The impact of EOT ctDNA status and RCB on event-free survival (EFS) and overall survival (OS) were estimated according to the Kaplan-Meier method and compared among groups by log-rank test, followed by Cox regression analysis. Results: For 47 TNBC patients with RD and available EOT plasma sample, the median age was 47 years, and 43% had node-positive disease at diagnosis. RCB class distribution was as follows: RCB I=28%, RCB II=49%, RCB III=15%, RCB unknown=8%. 45% of patients received adjuvant chemotherapy (59% with RCB II-III received adjuvant chemotherapy), and 68% received adjuvant radiation. EOT ctDNA was positive in 34% (16/47) of patients and was associated with higher T stage (p=0.012), TNM stage (p=0.033) and trend toward higher RCB class (p=0.078). ctDNA positivity rates in RCB I, II and III classes were 23%, 30% and 71%, respectively. Among all patients, 3-year EFS and OS were 71% and 73%, respectively. Table 1 provides 3-year EFS and OS by ctDNA status in all patients and by RCB class. ctDNA positive status was associated with inferior EFS and OS. Conclusion: EOT ctDNA positivity was noted in one-third of TNBC patients with residual disease and was highly prognostic, with almost half of patients with ctDNA positivity suffering an EFS event by 3 years. Patients with RCB III had very poor outcome (3-year EFS ≤20%) regardless of ctDNA status. However, in RCB classes I/II, ctDNA provided further prognostic utility, as ctDNA negative patients with RCB I/II had excellent outcomes (3-year EFS &amp;gt;90%). These findings should be confirmed in other studies and provide insights into the role of ctDNA for patient stratification/selection in residual disease adjuvant therapy intensification trials for TNBC. 3-year EFS3-year OSAll patients: ctDNA positive vs ctDNA negative56% vs 78%, HR 3.02 (95% CI: 1.01-9.01), p=0.03856% vs 82%, HR 3.05 (95% CI: 1.02-9.13), p=0.037RCB I/II: ctDNA positive vs ctDNA negative73% vs 92%, HR 4.38, p=0.07873% vs 92%, HR 3.03, p=0.159RCB III: ctDNA positive vs ctDNA negative0% vs 20%, HR 1.67, p=0.5610% vs 20%, HR 1.30, p=0.765 Citation Format: Priyanka Sharma, Shane R Stecklein, Bruce F Kimler, Rachel Yoder, Kelsey Schwensen, Joshua M Staley, Qamar J Khan, Anne P O'Dea, Lauren E Nye, Manana Elia, Jaimie Heldstab, Trisha Home, Stephen Hyter, Kamilla Isakova, Harsh B Pathak, Andrew K Godwin. Impact of post-treatment ctDNA and residual cancer burden (RCB) on outcomes in patients with triple-negative breast cancer (TNBC) and residual disease [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-01-05.