Abstract P1-02-01: Circulating tumor DNA analysis to predict relapse and overall survival in early breast cancer – Longer follow-up of a proof-of-principle study

Abstract

Abstract Background In a previous proof-of-principle study we demonstrated that detection of circulating tumour DNA (ctDNA) in the adjuvant setting, after completion of surgery and chemotherapy for early stage breast cancer, was associated with a high risk of early relapse. Here we present longer follow-up of the same series, to define the predictive power of ctDNA analysis for disease free survival, and assess the potential to predict overall survival. Methods We recruited a cohort of 55 women presenting with early stage, primary breast cancer, who were all scheduled to receive neo-adjuvant chemotherapy. The primary tumour was sequenced to identify somatic mutations, identifying at least one mutation in 43 patients. Mutations were tracked with digital PCR to identify ctDNA, in plasma samples taken either at a single post-surgical time point (2-6 weeks post-surgery) or with serial plasma samples taken every 6 months in the adjuvant setting. Results At a median 31.7 months follow-up, 42% (18/43) patients had relapsed. Detection of ctDNA at the single post-surgical time point was associated with poor disease free survival, HR=13.6 95%CI (4.5, 41.2) p<0.001, and overall survival HR=84.7 95%CI (9.8, 730.4) p<0.001. All patients with ctDNA detected in a single post-surgical time point relapsed and died in the follow-up period (7/7, 100% specificity), although the single post-surgery time point had modest 39% (7/18) sensitivity for relapse. Detection of ctDNA at any point in serial sampling was associated with poor disease free survival HR=25.7 95%CI (8.3, 79.8) p<0.001 and overall survival HR=47.1 95%CI (6.1, 366.1) p<0.001. All patients with ctDNA detected in a serial mutation tracking relapsed in the follow-up period (14/14, 100% specificity), with 78% (14/18) sensitivity for relapse. Sensitivity was limited by 3 cases of brain only relapse and one case of solitary ovarian relapse. Detection of ctDNA in serial sampling had a median lead-time of 8.1 months over clinical relapse. Conclusion Detection of ctDNA in the adjuvant setting has a high predictive power for future relapse and death from breast cancer. Therapeutic trials are required to determine whether mutation tracking identifies relapse sufficiently early to allow for further adjuvant therapy. Citation Format: Turner NC, Garcia-Murillas I, Chopra N, Beaney M, Kilburn L, Cutts R, Osin P, Nerurkar A, Schiavon G, Hrebien S, Bliss J, Dowsett M, Smith I. Circulating tumor DNA analysis to predict relapse and overall survival in early breast cancer – Longer follow-up of a proof-of-principle study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-02-01.