Clinical significance of circulating tumor DNA testing for neoadjuvant chemotherapy in HER-2-negative stage Ⅱ/Ⅲ breast cancer
Objective To investigate the clinical significance of detecting circulating tumor DNA(ctDNA)in human epidermal growth factor receptor(HER)-2 negative(-)breast cancer patients undergoing neoadjuvant chemotherapy(NACT).Methods From March 2018 to March 2023,156 patients with stage Ⅱ/Ⅲ breast cancer with HER-2(-)were prospectively enrolled,including 72 patients with triple-negative breast cancer(TNBC)and 84 patients with hormone receptor(HR)(+)HER-2(-).All patients received standard NACT followed by surgery.The level and positive expression of ctDNA before NACT treatment(T0),3 weeks after treatment(T1),12 weeks after treatment(T2)and on the day of surgery(T3)were detected by second-generation sequencing.ctDNA differences between groups and time points were compared,and the relationship between ctDNA and treatment response and prognosis was analyzed.Results There were significant differences in pathological grade,pathological complete response(pCR)rate and residual cancer burden(RCB)grade between TNBC patients and HR(+)HER-2(-)patients(P＜0.05).In the TNBC group,the ctDNA mean tumor molecule(MTM)and ctDNA positive rates of patients with T1,T2 and T3 time-point pCR and non-pCR,and the ctDNA positive rates of patients with different RCB grades were statistically significant(P＜0.05).The median distant relapse-free survival(DRFS)of the whole group was 1208.50 days(range:137-2190 days),and 25.64％of the patients had distant metastasis.The results of univariate Cox proportional regression analysis showed that T stage,pCR,RCB grade and positive ctDNA at T0-T3 were the factors influencing DRFS in breast cancer patients(P＜0.05).Multivariate Cox proportional regression analysis showed that ctDNA positivity at T3 was an independent factor affecting DRFS of breast cancer patients(P＜0.05).The DRFS of patients who received pCR and T3 time point ctDNA negative were longer than those of patients with non-pCR and T3 time point ctDNA negative or non-pCR and T3 time point ctDNA positive(P＜0.05).The DRFS of RCB 0-1 patients with negative ctDNA at T3 were longer than those of RCB 2-3 patients with negative ctDNA at T3 or RCB 2-3 patients with positive ctDNA at T3(P＜0.05).Conclusion Monitoring the dynamics of ctDNA in operable HER-2(-)stage Ⅱ/Ⅲ breast cancer patients prior to NACT treatment is feasible and helps clinicians evaluate NACT treatment response and prognosis.
Breast cancerHuman epidermal growth factor receptor-2(HER-2)Neoadjuvant chemotherapy(NACT)Circulating tumor DNA(ctDNA)
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