Purpose: To comparing the survival in different strategies, preoperative systemic treatment (PST) versus upfront surgery (US) in patients of HER2-positive early breast cancer in real-world.Methods: Eligible patients from 2012 to 2015 were classified as PST or US group prospectively, according to the real upfront treatment. The primary endpoint is disease-free survival (DFS), the second endpoint is overall survival (OS). All the outcomes were examined in unadjusted model, propensity score matching (PSM) model, and inverse probability of treatment weighting (IPTW) model. Results: Finally, 1067 eligible patients (215 in PST group, 852 in US group) were included into analysis (Table 1). In unweighted analysis, the cumulative DFS of PST group was significantly lower than US group (78.1% vs 87.7%, P<0.001), especially for those did not reach pathological complete response after PST. After adjusting the parameters, in PSM model (matching at 1:1 ratio), the DFS of PST group was significantly higher than the DFS of US group (HR, 0.57s2, 95%CI, 0.371~0.881, P, 0.012). In IPTW model, there was no significant difference of DFS between two groups (HR, 0.946, 95%CI, 0.763~1.172, P, 0.609). For OS, there were no significant difference between two groups in all three models. Conclusions: The patients in PST group have worse DFS than those in US group, mainly because of the unbalancing stage and biological risk. By real-world statistic method, after adjusting and making parameters comparable, the DFS of PST group is non-inferiority to the DFS of US group in IPTW model and even superior to US group in PSM model.

*Proportions and medians are weighted using IPTW, all covariates included in the propensity analysis. Abbreviations: PSM, propensity score matching, IPTW, inverse probability of treatment weighting, PST, preoperative systemic treatment, US, upfront surgery, SMD, standardized mean difference, ER, estrogen receptor, PR, progesterone receptor.In IPTW model, the DFS rate of the PST group was 81.3% versus 80.8% of the US group, and the OS rate of the PST group was 92.1% versus 90.3% (Figure 2E, 2F), both having no significantly differences (Table 4). In further stratified analysis (Figure 3E, 3F), as in PSM model, the DFS and OS rate of the patients without pCR after PST (73.1%, 88.4%) were worse than those with pCR (96.6%, 99.3%) and US group (80.8%, 90.3%), respectively.

Table 1. The clinicopathologic characteristics of two groups in PSM and IPTW models

CharacteristicsNumber of casesUnweighted primary samplePSM modelIPTW model*
PST group (215)US group (852)SMDPST group (145)US group (145)SMDPST group (765)US group (1021)SMD
N (%)N (%)N (%)N (%)N (%)N (%)
Age (years, medium, 95%CI) 50, 39~61 50, 33~64 0.05 50, 40~65 49, 34~62 0.10 49, 39~67 50, 31~64 0.03 
Stage T 458 8 (3.7) 450 (52.8) 0.701 8(3.7) 10 (6.9) 0.032 80 (10.5) 450 (44.1) 0.467  
 529 157 (73.0) 372 (43.7)  118 (81.4) 116 (80.0)  635 (83.0) 458 (44.9)   
 80 50 (23.3) 30 (3.5)  19 (13.1) 19 (13.1)  50 (6.5) 113 (11.1)   
Stage N 571 37 (17.2) 534 (62.7) 1.048 37 (17.2) 32 (22.1) 0.081 310 (40.5) 538 (52.7) 0.246  
 596 178 (82.8) 318 (37.3)  108 (81.4) 113 (77.9)  455 (59.5) 483 (47.3)   
Grade 1 and 2 522 92 (42.8) 430 (50.5) 0.154 77 (53.1) 89 (61.4) 0.168 345 (45.1) 493 (48.3) 0.064  
 545 123 (57.2) 422 (49.5)  68 (46.9) 56 (38.6)  420 (54.9) 528 (51.7)   
ER Negative 536 142 (66.0) 394 (46.2) 0.407 87 (60.0) 68 (46.9) 0.265 386 (50.5) 513 (50.2) 0.004  
 Positive 531 73 (34.0) 458 (53.8)  58 (40.0) 77 (53.1)  379 (49.5) 508 (49.8)   
PR Negative 649 171 (79.5) 478 (56.1) 0.418 108 (74.5) 113 (77.9) 0.081 499 (65.2) 625 (61.2) 0.083  
 Positive 418 44 (20.5) 374 (43.9)  37 (25.5) 32 (22.1)  266 (34.8) 396 (38.8)   
CharacteristicsNumber of casesUnweighted primary samplePSM modelIPTW model*
PST group (215)US group (852)SMDPST group (145)US group (145)SMDPST group (765)US group (1021)SMD
N (%)N (%)N (%)N (%)N (%)N (%)
Age (years, medium, 95%CI) 50, 39~61 50, 33~64 0.05 50, 40~65 49, 34~62 0.10 49, 39~67 50, 31~64 0.03 
Stage T 458 8 (3.7) 450 (52.8) 0.701 8(3.7) 10 (6.9) 0.032 80 (10.5) 450 (44.1) 0.467  
 529 157 (73.0) 372 (43.7)  118 (81.4) 116 (80.0)  635 (83.0) 458 (44.9)   
 80 50 (23.3) 30 (3.5)  19 (13.1) 19 (13.1)  50 (6.5) 113 (11.1)   
Stage N 571 37 (17.2) 534 (62.7) 1.048 37 (17.2) 32 (22.1) 0.081 310 (40.5) 538 (52.7) 0.246  
 596 178 (82.8) 318 (37.3)  108 (81.4) 113 (77.9)  455 (59.5) 483 (47.3)   
Grade 1 and 2 522 92 (42.8) 430 (50.5) 0.154 77 (53.1) 89 (61.4) 0.168 345 (45.1) 493 (48.3) 0.064  
 545 123 (57.2) 422 (49.5)  68 (46.9) 56 (38.6)  420 (54.9) 528 (51.7)   
ER Negative 536 142 (66.0) 394 (46.2) 0.407 87 (60.0) 68 (46.9) 0.265 386 (50.5) 513 (50.2) 0.004  
 Positive 531 73 (34.0) 458 (53.8)  58 (40.0) 77 (53.1)  379 (49.5) 508 (49.8)   
PR Negative 649 171 (79.5) 478 (56.1) 0.418 108 (74.5) 113 (77.9) 0.081 499 (65.2) 625 (61.2) 0.083  
 Positive 418 44 (20.5) 374 (43.9)  37 (25.5) 32 (22.1)  266 (34.8) 396 (38.8)   

Citation Format: Yang Hongjian, Xingfei Yu, Chen Wang, Zheng Yabing, Hu Jiejie, Xiying Shao, Liming Sheng, Juan Lin, Yuqin Ding, Haojun Xuan, Lijie Gong, Weiliang Feng, Chengdong Qin, Daobao Chen, Yang Yu. Preoperative systemic therapy versus upfront surgery in HER2-positive early breast cancer: A prospective nested case-control study in the real world [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-52.