Comparison of neoadjuvant TCbHP versus THP in HER2-positive breast cancer: a retrospective cohort study

Background: Although the Chinese Society of Clinical Oncology (CSCO) guidelines list both the TCbHP regimen (taxane + carboplatin + trastuzumab + pertuzumab) and the carboplatin-sparing THP regimen (taxane + trastuzumab + pertuzumab) as category I neoadjuvant recommendations for human epidermal growth factor receptor 2 (HER2)-positive breast cancer, TCbHP carries a significantly higher toxicity burden, and current guidelines do not clearly define which patients can safely omit platinum. Accordingly, this study aims to compare the efficacy and long-term outcomes of neoadjuvant TCbHP versus THP in HER2-positive breast cancer and to preliminarily identify patients who may safely forgo carboplatin.

Methods: This retrospective cohort study included patients with HER2-positive breast cancer who received neoadjuvant TCbHP or THP at Tianjin Medical University Cancer Institute and Hospital between January 2019 and December 2022. Inclusion criteria were age 18 years, clinical stage II-III disease, completion of six cycles of neoadjuvant therapy (NAT), and no prior anticancer treatment or distant metastasis at diagnosis. Baseline clinicopathological characteristics were extracted from electronic medical records. The primary endpoint was pathological complete response (pCR). Secondary endpoints were event-free survival (EFS) and disease-free survival (DFS). Follow-up was conducted via outpatient records and telephone interviews, with data censored on June 30, 2025.

Results: Of 427 screened patients, 148 matched pairs were generated by 1:1 propensity score matching using age, menopausal status, clinical T stage, lymph node status, HR status, HER2 status, Ki-67 and taxane. There was no significant difference in pCR rates between TCbHP and THP (53.4% vs. 43.2%, P=0.08). Exploratory subgroup analyses showed a significant benefit for the TCbHP regimen over the THP regimen in patients aged ≤60 years [odds ratio (OR) =0.56; 95% confidence interval (CI): 0.33–0.93; P=0.03], premenopausal patients (OR =0.47; 95% CI: 0.24–0.91; P=0.03), and those with Ki-67 >30% (OR =0.48; 95% CI: 0.28–0.82; P=0.007). But formal interaction tests revealed a statistically significant interaction only between the two Ki-67 subgroups (P for interaction =0.02). The estimated 3-year EFS rates were 96.6% (95% CI: 93.8–99.6%) in the TCbHP group and 96.0% (95% CI: 92.8–99.2%) in the THP group, with no significant difference between the two regimens [hazard ratio (HR) =1.26; 95% CI: 0.47–3.40; P=0.64].

Conclusions: No significant difference in efficacy or 3-year EFS was observed between TCbHP and THP. Exploratory subgroup analyses showed that TCbHP achieved a higher pCR rate than THP in patients aged ≤60 years, premenopausal patients, and those with Ki‑67 >30%. Furthermore, interaction tests suggested that patients with Ki‑67 >30% derived a greater benefit from the TCbHP regimen compared with those with Ki‑67 ≤30%.