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. 2022 Jun;148(6):1543-1550.
doi: 10.1007/s00432-022-03990-7. Epub 2022 Apr 9.

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

E La Rocca #  1   2 , M C De Santis  1   2 , M Silvestri #  3 , E Ortolan  3 , M Valenti  3 , S Folli  1   4 , F G de Braud  1   5   6 , G V Bianchi  1   5 , G P Scaperrotta  1   7 , G Apolone  8 , M G Daidone  8 , V Cappelletti  3 , G Pruneri #  1   6   9 , S Di Cosimo #  10
Affiliations

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

E La Rocca et al. J Cancer Res Clin Oncol. 2022 Jun.

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.

Keywords: Breast cancer; Circulating tumor DNA; Follow-up; Imaging.

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Conflict of interest statement

ELR, MCD, MS, EO, MV, SF, GVB, GS, GA, MGD, and VC: none; FGdB: speakers bureau honoraria from BMS, Eli Lilly, Roche, Amgen, AstraZeneca, Gentili, Fondazione Menarini, Novartis, MSD, Ignyta, Bayer, Noema SRL, ACCMED, DEPHAFORUM SRL, Nadirex, Roche, Biotechspert Ltd., PriME Oncology, Pfizer, consultant/advisory board fees from BMS, Tiziana Life Sciences, Celgene, Novartis, Servier, Phanm Research Associated, Daiichi Sankyo, Ignyta, Amgen, Pfizer, Roche, Teogarms, and Pierre Fabre; GP: honoraria from Roche, GSK, Genomic Health, and Hybrid Genetic; SDC: consulting fees from Pierre-Fabre, IQVIA.

Figures

Fig. 1
Fig. 1
a Histograms show the number and percentage of non-recommended imaging services by type; b Box plots report the number of non-recommended imaging services according to patient age and tumor stage
Fig. 2
Fig. 2
Bar plot reports the number of follow-up procedures for each patient as negative (pale brown), suspected for malignancy (orange), or diagnostic of recurrence (bordeaux). The heatmap columns report the results of ctDNA assessment for each patient of the study cohort before surgery and at intervals of 4–6 months (T1, T2, Tn) during follow-up as detectable (red), undetectable (blue), or missing (white). Breast cancer event occurrence (black) or absence (grey) is reported as a bar on the bottom of the figure. To be noted: patient #10 had a second primary breast cancer at prophylactic contralateral mastectomy; patient #21 died for causes unrelated to cancer and its treatment; patients #1, #2, #8 and #30 lack ctDNA information due to wild type primary tumors; patients #5 and #31–33 are not reported due to non-evaluable primary tumor mutational profile
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