Analysis of eddicacy of HER2-enriched subtype to Trastuzumab combined with Lapatinib in treatment of early breast cancer

Abstract

Objective To analyze the therapeutic effects of adjuvant therapy with the human epidermal growth factor receptor 2 (HER2) double-blocker Trastuzumab and Lapatinib on the differential expression of different molecular subtypes of breast cancer, especially for the HER2 overexpression. Methods A prospective study was conducted to select 227 patients with early-stage HER2-positive breast cancer who were not treated in the Yulin First Hospital from January 2014 to March 2017. The average age was 55 years old, rang from 22 to 67 years old. All patients received a double blocker treatment for consecutive 18 weeks [oral Lapatinib 1 000 mg/(time·d) and injection Trastuzumab (first 8 mg/kg, later 6 mg/kg, Intravenous drip, once every 3 weeks)]. Among them, postmenopausal patients took Letrozole 2.5 mg/d, and premenopausal patients took Tamoxifen 20 mg/d. If a serious adverse reaction occurs during the administration, the amount of Lapatinib was reduced to 750 mg/(time·d). The test can continue after the adverse reaction had dropped to level 1 and below, up to 14 days. Safety tests were performed on the first day of each cycle, and biopsy was performed on the 14th day for the detection of initial gene expression changes, and the effect of the reaction was initially judged by ultrasound at 6th week. According to the Response Evaluation Criteria in Solid Tumors 1.1 of the solid tumor, if the tumor volume becomes large, it was determined that the treatment was ineffective. Ineffective patients were given an intravenous infusion of 80 mg/m2 Paclitaxel per week. The dose of lapatinib was reduced to 750 mg/(time·d) and the remaining 12 courses were continued. Normal patients underwent surgery within 1 to 3 weeks of the completion of the last course of treatment. Ineffective patients underwent surgery within 2 to 3 weeks after the end of the procedure, and the last safety examination was followed up 30 days after surgery. Clinical variables, complete response rates, and adverse events were observed in patients with different molecular subtypes. Measurement data were expressed as median (interquartile range) [M(P25, P75)], Wilcoxon rank sum test was used for comparison between groups; Chi-square test was used for compare the count data between groups. Results Of the 227 patients, 207 (91.19%) completed the entire treatment process. After treatment, compared with the initial molecular subtypes, 63 (41.72%) of the 151 patients with HER2 overexpression had complete remission, while only 10 of the 76 other subtypes (13.16%) were completely relapsed. Remission, the difference between the two groups was statistically significant (χ2=17.62, P<0.001); after 14 days of treatment, most of the tumor types were converted to normal breast-like type, and the patients who became normal breast-like type were completely, the response rate was 50.00% (56/112), which was much higher than the complete response rate of other patients [14.78% (17/115), χ2=30.66, P<0.001]. Of the initial 151 HER2 overexpressing patients, 115 (76.16%) patients switched to other subtypes, of which 84 (73.04%) converted to normal breast-like and 51 (60.71%) for complete remission. Most of the adverse reactions were concentrated in grades 1 to 2. Among them, liver function abnormalities, diarrhea, skin rashes, and hand-foot syndrome were the main factors. Conclusion In HER2-positive early breast cancer, adjuvant therapy with the HER2 double-blocker Trastuzumab and Lapatinib is more effective in patients with HER2 overexpression and can be used to determine the intrinsic molecular subtype of breast cancer, with its potential utilization value. Key words: Breast neoplasms; Genotype; Trastuzumab; Lapatinib