Abstract P2-11-26: The prognostic role of circulating tumor DNA after neoadjuvant chemotherapy in triple negative breast cancer with residual tumor
Authors: Roseshter Talia , Klemantovich Anna , Cavallone Luca , Aguilar-Mahecha Adriana , Lafleur Josiane , Elebute Oluwadara O. , Jenna Sarah , Boileau Jean-Francois , Pelmus Manuela , Basik Mark , Lan Cathy 
Published: March 2023

Abstract
Background The presence of residual tumour at surgery (non-pathological complete response or non-pCR) occurs in about half of TNBCs treated with neoadjuvant chemotherapy (NAC) and signals chemoresistance and poor prognosis. Although further adjuvant chemotherapy (Capecitabine/Xeloda) results in improved survival in patients with non-pCR, only about 15% of such patients do benefit. Circulating tumor DNA (ctDNA) is a plasma-based biomarker that can be used to reveal real-time data about the disease and treatment progression. We have previously shown that detection of ctDNA after NAC signals poor prognosis. To validate and extend our previous results using an academic hospital-based tumor bespoke assay, we performed ctDNA measurements in non-pCR TNBC patients at the pre-operative, post-operative, 3 and 6-month time points. Methods Whole exome sequencing (WES) was performed on residual tumors from 34 TNBC patients to identify tumour-specific mutations (5/patient). Digital droplet PCR (ddPCR) assays were developed for these mutations and performed as per our previous work. Patients with at least one detectable mutation were considered ctDNA positive for a given time point. The detection of ctDNA was correlated with relapse-free survival (RFS). Results The overall RFS was 44%, with 56 % of patients received adjuvant Xeloda. Detection of ctDNA at the end of NAC (T1) correlated with poor prognosis of RFS (n = 33, p-value = 0.009, HR = 0.29 (95% CI = 0.12 to 0.74)). Detection of ctDNA after surgery (T2) and while on Xeloda (T3) showed no significant prognostic value for RFS. However, ctDNA detection at the 6-month time point, after Xeloda treatment (T4), showed stronger prognostic value for RFS (n = 17, p-value = 0.004, HR = 0.12 (95% CI = 0.03 to 0.51)). When measuring changes in ctDNA detectability from T1 to T4, 4 patients initially positive became ctDNA negative after the 6-month interval, and only 1 of these 4 had a relapse, compared with 10 of 11 that remained positive at the 6-month time point (p = 0.01, Chi-squared test). 3 of the 4 patients that cleared their ctDNA had received Xeloda. In addition, 2 patients initially negative became ctDNA positive at the 6-month time point (T4) and both relapsed, compared with only 1 of 5 that remained negative at 6 months (p = 0.035, Chi-squared test). For patients who received adjuvant Xeloda ctDNA positivity at T1 was associated with a worse RFS (p-value = 0.028, HR = 3.3884 (95% CI = 1.160 to 13.00)). Conclusion ctDNA testing using ddPCR in an academic hospital-based context at the post-NAC time point as well as at 6 months after surgery identifies an excellent prognostic group in TNBC patients with non-pCR and changes in ctDNA during the adjuvant period have prognostic value. This personalized approach to treatment management is ready for prospective testing in patients who have undergone NAC and require additional chemotherapy.
Citation Format: Talia Roseshter, Anna Klemantovich, Luca Cavallone, Adriana Aguilar-Mahecha, Josiane Lafleur, Oluwadara O. Elebute, Sarah Jenna, Jean-Francois Boileau, Manuela Pelmus, Mark Basik, Cathy Lan. The prognostic role of circulating tumor DNA after neoadjuvant chemotherapy in triple negative breast cancer with residual tumor [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-26.