Early stage breast cancer follow-up in real-world clinical practice: the added value of cell free circulating tumor DNA

Abstract

Purpose Physical examinations and annual mammography (minimal follow-up) are as effective as laboratory/imaging tests (intensive follow-up) in detecting breast cancer (BC) recurrence. This statement is now challenged by the availability of new diagnostic tools for asymptomatic cases. Herein, we analyzed current practices and circulating tumor DNA (ctDNA) in monitoring high-risk BC patients treated with curative intent in a comprehensive cancer center. Patients and methods Forty-two consecutive triple negative BC patients undergoing neoadjuvant therapy and surgery were prospectively enrolled. Data from plasma samples and surveillance procedures were analyzed to report the diagnostic pattern of relapsed cases, i.e., by symptoms, follow-up procedures and ctDNA. Results Besides minimal follow-up, 97% and 79% of patients had at least 1 non-recommended imaging and laboratory tests for surveillance purposes. During a median follow-up of 5.1(IQR, 4.1–5.9) years, 13 events occurred (1 contralateral BC, 1 loco-regional recurrence, 10 metastases, and 1 death). Five recurrent cases were diagnosed by intensive follow-up, 5 by symptoms, and 2 incidentally. ctDNA antedated disseminated disease in all evaluable cases excepted two with bone-only and single liver metastases. The mean time from ctDNA detection to suspicious findings at follow-up imaging was 3.81(SD, 2.68), and to definitive recurrence diagnosis 8(SD, 2.98) months. ctDNA was undetectable in the absence of disease and in two suspected cases not subsequently confirmed. Conclusions Some relapses are still symptomatic despite the extensive use of intensive follow-up. ctDNA is a specific test, sensitive enough to detect recurrence before other methods, suitable for clarifying equivocal imaging, and exploitable for salvage therapy in asymptomatic BC survivors.

Circulating tumor DNA: from discovery to clinical application in breast cancer

“…They found that in nearly all evaluated cases (with the exception of a few cases involving bone or liver metastases), ctDNA became detectable before any signs of disease spread. Moreover, the average time from ctDNA detection to the identification of suspicious findings on follow-up imaging was approximately 3.81 months, with a mean time to a definitive recurrence diagnosis of 8 months ( 116 ). Similarly, another study involving serial ctDNA testing in patients with early-stage breast cancer who had undergone neoadjuvant chemotherapy (post/preoperative) showed that the detection of ctDNA during follow-up was strongly associated with disease recurrence.…”

Association of ctDNA detection and recurrence assessment in patients with neoadjuvant treatment

“…In the sensitivity analysis, the resulting trends remained the same as those in the above analysis after removing the five low-quality comparisons, as shown in Figure S1. 15,18,21,24,32 (HR: 5.42, 95% CI: 3.34-8.75, p < 0.001, I 2 = 51%) The NOS scores of 23 included literatures ranged from 5 to 9. Funnel plots were chosen to estimate publication bias in this study and no obvious bias was observed.…”