Preoperative Dose-dense Chemotherapy Or Postoperative Chemotherapy For Operative Triple Negative Or HER2-positive Breast Cancer:A Randomized Study

Purpose:The study aims to investigate the survival of using preoperative versus postoperative chemotherapy in patient with Triple Negative Breast Cancer(TNBC)or HER2-positive Operable Breast Cancer,and explore an optimal treatment model for TNBC and HER2-positive operable Breast Cancer.Method:It’s a prospective,single-center,randomized controlled phase II clinical study.Patients with core needle biopsy confirmed pathological diagnosis of stage T1-3N0-2M0 Triple Negative or HER2-positive Breast Cancer were 1:1 randomized to preoperative group or postoperative group.TNBC patients in preoperative group receive paclitaxel(175mg/m2,day1)plus carboplatin(Area Uder the Curve=4,day2)every two weeks for 6 cycles.HER2-positive patients in preoperative group receive the same regimens as for TNBC plus trastuzumab 4mg/kg loading dose followed by 2mg/kg in combination for every week,followed by an additional 6mg/kg every 3 weeks for 1 year.Patients in postoperative group receive standard chemotherapy regimens according to risk of recurrence.The primary endpoint was Relapse-free survival(RFS)for preoperative and postoperative group.The secondary endpoints included overall survival(OS),pathological complete response(pCR)rate,association between pCR and RFS or OS and safety.Result:Between November,2013 and April,2018,For TNBC,a total of 150 cases were planned and 107 were actually enrolled(53 preoperative and 54 postoperative)with a median age of 46years(range 25-75 years).The median follow-up time was 27.1 months.The median RFS has not been reached.4 patients developed local recurrence or distant metastasis in preoperative group and 12 in postoperative goup.3-year RFS were higher in preoperative group(89.3%vs 73.8%),but no significant difference were observed(p=0.19).Among 44 patients who received surgery,16 patients obtained pCR,with a pCR rate of 36.4%.Patients who achieved pCR were free of rucurrence.The most common adverse events in preoperative group was neutropenia,Grade 3/4 incidence rate was 44.7%.Other events included ALT/AST elevation(53.2%)and Peripheral eurotoxicity(30.4%).For HER2-positive Breast Cancer,a total of 80 cases were planned and 67 were actually enrolled(33 preoperative and 34 postoperative)with a median age of 49 years(range 20-73 years).The median follow-up time was 25.1 months.The median RFS has not been reached.2 patients developed local recurrence or distant metastasis in preoperative and 2 in postoperative.3-year RFS were similar in preoperative group(88.9%vs 89.7%,p=0.902).Among 31 patients who received surgery,11 patients obtained pCR,with a pCR rate of 35.5%,Patients who achieved pCR were free of rucurrence.The most common adverse events in preoperative group was neutropenia,Grade 3/4 incidence rate was 39.4%.Other events included ALT/AST elevation(46.9%)and Peripheral neurotoxicity(46.8%).Conclusion:This priliminary results show the recurrence was significantly less in preoperative group than in postoperative group,3-year RFS in preoperative group were higher than in postoperative group,there may be a tendency to benefit in preoperative group.Due to the few number recurrence in HER2 positive breast cancer,3-year RFS were similar in two group in HER2-positive.patients who achieved pCR were free of recurence,suggested pCR predict favorable prognosis.Dose-dense regimens in neoadjuvant setting were well tolerance.It is still necessary to continue to recruit patients and follow up to draw a clear conclusion.