PROGNOSTIC VALUE OF CIRCULATION TUMOR DNA DOSING IN PATIENTS IN NEOADJUVANT BREAST NEOPLASIA (GI-RO-CTDNA)

Background: Pathologic Complete Response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer is strongly associated with a favorable prognosis. We evaluated whether there is a correlation between serum levels of circulating tumor DNA (ctDNA) during neoadjuvant therapy with obtaining pCR and detection of residual disease after treatment. Patients and Methods: ctDNA was isolated from 310 plasma samples of 27 patients diagnosed with localized and/or locally advanced breast cancer treated with standard NAC alone or combined with immunotherapy and/or anti-HER 2- targeted therapy when indicated. Blood was collected at pretreatment, every 15 days during treatment and before surgery. Results: Eight (29%) of the 27 patients presented pCR, 4 triple negative (50%, 3 HER2+ (37%) and 1 (13%) luminal B. We observed that throughout the neoadjuvant treatment in the seventh collection the ctDNA levels were significantly higher in patients who did not presented pCR in relation to those who achieved it, p-value = 0.014.62.5% of patients who presented pCR in the surgical specimen also had a complete radiological response, with a significant correlation, p-value = 0.02492. Although we did not find statistical significance, we did note that patients who presented pCR had a tendency towards an initial increase in their ctDNA levels after the first cycle of chemotherapy. The finding of increased ctDNA levels soon after the initiation of anti-Her2 therapy in Her2-positive patients, even during neoadjuvant treatment, seems to indicate that it would be possible that the increase in ctDNA soon after an effective therapy could indicate tumor sensitivity by increasing death cell and the release of ctDNA into the circulation. Conclusions: ctDNA dosage in the third month (seventh collection) of neoadjuvant treatment is inversely correlated with the achievement of tumor pCR and that studies with a larger number of patients will serve to clarify whether there is prognostic or predictive value of an initial increase in concentrations of ctDNA after neoadjuvant treatment that was often seen especially in pacients’s presented pCR.