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

Introduction

Neoadjuvant therapy (NAT) is now standard for locally advanced or down-stageable human epidermal growth factor receptor 2 (HER2)-positive breast cancer (1). Achieving pathological complete response (pCR) consistently predicts superior long-term survival, validating pCR as a reliable surrogate endpoint (2,3). The phase III NeoSphere (4,5) and PEONY (6,7) established the cornerstone role of dual-targeted therapy (trastuzumab + pertuzumab) combined with taxanes, raising pCR rates and improving long-term outcomes. Anthracycline-containing regimens can further increase pCR, but excess cardiotoxicity limits their use. The TRAIN-2 (8) and TRYPHAENA (9,10) studies demonstrated that the anthracycline-free TCbHP regimen (taxane + carboplatin + trastuzumab + pertuzumab) is non-inferior for pCR and significantly reduces left-ventricular ejection-fraction decline. The KRISTINE (11) trial also showed TCbHP improved pCR versus T-DM1 + pertuzumab (55.7% vs. 44.4%), albeit with more haematologic toxicity and peripheral neuropathy. Consequently, TCbHP is endorsed as a preferred regimen in major guidelines, yet dose modifications and treatment interruptions driven by its high toxicity burden continue to compromise adherence.

In recent years, driven by the precision-oncology agenda, treatment de-escalation has become a central theme in HER2-positive breast cancer. In the metastatic setting, BCIRG-007 (12) showed that adding carboplatin to docetaxel plus trastuzumab did not improve the response rate or progression-free survival, HELEN-006 (13) demonstrated that weekly nab-paclitaxel combined with dual anti-HER2 therapy achieved a superior pCR rate compared with TCbHP (63.4% vs. 48.6%, P=0.002). The phase III neoCARHP trial (14), provided important evidence. This Chinese multicenter study enrolled 774 patients with stage II–III HER2-positive breast cancer who were randomly assigned to neoadjuvant TCbHP or THP. The results showed a pCR rate of 64.1% in the THP group and 65.9% in the TCbHP group (difference −1.8%; non-inferiority P=0.009), while the incidence of grade 3–4 adverse events was significantly lower with THP (20.7% vs. 34.6%). These findings challenge the necessity of adding carboplatin in HER2-positive breast cancer.

Long-term follow-up data from the KATHERINE trial confirmed that (15), among patients with residual invasive disease after NAT, adjuvant T-DM1 significantly improved overall survival [hazard ratio (HR) =0.66, 95% confidence interval (CI): 0.51–0.87, P=0.003] and invasive disease-free survival (DFS) (HR =0.54, 95% CI: 0.44–0.66) compared with trastuzumab, with an absolute gain of 4.7 percentage points in 7-year overall survival. This implies that even if pCR is not achieved with initial NAT, subsequent T-DM1-based adjuvant intensification can still substantially improve patient outcomes. Consequently, the survival value of the toxicity incurred by adding carboplatin to marginally increase pCR may no longer be as irreplaceable as previously thought.

However, current American Society of Clinical Oncology (ASCO) (1) and European Society for Medical Oncology (ESMO) (16) guidelines both recommend dual HER2 blockade combined with chemotherapy as the standard neoadjuvant strategy for HER2-positive breast cancer. Multiple European studies and consensus statements further favor carboplatin-containing, anthracycline-free dual-antibody regimens as one of the preferred options (17), while the carboplatin-sparing THP regimen still lacks clear stratified recommendations in these guidelines. In the 2024 Chinese Society of Clinical Oncology (CSCO) guidelines (18), both six-cycle TCbHP and THP are listed as category I recommendations. The guidelines state that TCbHP is the preferred neoadjuvant regimen, but THP may be considered for patients aged >60 years, those with low tumor burden, or those unable to tolerate platinum-containing combinations due to poor general condition. Thus, there remains a lack of consensus on whether and in which patients carboplatin can be safely omitted.

To our knowledge, head-to-head studies directly comparing the efficacy and long-term survival of TCbHP versus THP remain very limited. Accordingly, this study retrospectively compares the efficacy and long-term prognosis of TCbHP versus THP as NAT for HER2-positive breast cancer, providing real-world retrospective evidence for the neoCARHP trial and complementing its long-term survival outcomes. It also aims to identify patient subsets in whom carboplatin can be safely omitted, thereby offering evidence-based support for individualized de-escalation treatment decisions. We present this article in accordance with the STROBE reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0111/rc).

Methods

Study design and patients

This was a single-center retrospective cohort study, aimed at investigating the efficacy and prognosis of two neoadjuvant regimens, TCbHP and THP, in HER2-positive breast cancer. Patients were divided into the TCbHP group and the THP group according to the treatment regimen received. The primary outcome was the pCR rate, and the secondary outcomes were the 3-year EFS rate and the 3-year DFS rate. Additionally, exploratory subgroup analyses were conducted to identify patient populations that might derive greater benefit from the TCbHP regimen.

Patients with HER2-positive invasive breast cancer who received six cycles of TCbHP or THP NAT at Tianjin Medical University Cancer Institute and Hospital between January 2019 and December 2022 were included in this study. The number of cases in the area during the study period determined the sample size. The last follow-up was censored on 30 June 2025.

Inclusion criteria were as follows: (I) female and over 18 years of age; (II) pathologically diagnosed with HER2-positive invasive breast cancer via core needle biopsy; (III) clinical stage II–III disease; (IV) with indications of NAT and completed six cycles of TCbHP or THP treatment; (V) Eastern Cooperative Oncology Group (ECOG) performance status 0–1; (VI) a baseline left ventricular ejection fraction ≥50%. Exclusion criteria were as follows: (I) use of any neoadjuvant regimen other than TCbHP or THP; (II) incomplete clinical or pathological data; (III) local recurrence or distant metastasis at diagnosis; (IV) non-adherence to guideline-recommended surgery or adjuvant therapy; (V) second primary tumor or prior anticancer treatment; (VI) clinically significant comorbidities precluding protocol therapy. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Medical Ethics Committee of Tianjin Medical University Cancer Institute and Hospital (No. bc20262149) and individual consent for this retrospective analysis was waived.

Clinicopathological characteristics

The clinicopathological characteristics included in this study were age at diagnosis, menopausal status, clinical T stage, and lymph node status. Regarding age at diagnosis, based on relevant studies and clinical guidelines, we used 60 years as cutoff values for subgroup analyses (13,16).

Immunohistochemical (IHC) interpretation was based on the following criteria: (I) estrogen receptor (ER)/progesterone receptor (PR) status: nuclear staining in ≥1% of tumor cells was considered positive; <1% was negative. ER and/or PR positive was classified as hormone receptor (HR) positive; ER and PR negative is classified as HR negative; (II) HER2 status: HER2 positivity was defined as IHC 3+ or IHC 2+ with confirmatory gene amplification by fluorescence in situ hybridization (FISH); (III) Ki-67 expression: a threshold of 30% was applied, as recommended by the International Ki-67 in Breast Cancer Working Group (19). Tumors with Ki-67 ≥30% were categorized as having high proliferation, whereas those <30% were considered low.

Scheme of treatment

All enrolled patients received standard neoadjuvant regimens recommended by the CSCO guidelines: (I) six cycles of TCbHP; or (II) six cycles of THP. The taxanes administered included docetaxel, nab‑paclitaxel, and paclitaxel. Drug dosages and administration intervals strictly adhered to CSCO recommendations. Surgery was performed 3–4 weeks after completion of NAT. Breast surgery options included mastectomy or breast-conserving surgery, and axillary management included axillary lymph node dissection (ALND) or sentinel lymph node biopsy (SLNB). The final surgical approach was individualized according to tumor characteristics and patient preference. Patients achieving pCR completed one year of adjuvant trastuzumab + pertuzumab; those with residual disease received T-DM1 intensification.

Efficacy assessment and survival analysis

The primary endpoint was pCR, defined as the absence of residual invasive cancer in the primary breast tumor [ductal carcinoma in situ (DCIS) was permitted] and negative regional lymph nodes (ypT0/is ypN0). The secondary endpoints were DFS and event-free survival (EFS). DFS was defined as the time from the date of surgery (first date of no disease) to the first documentation of disease recurrence (local, regional, distant, or contralateral) or death from any cause. EFS was defined as the time from NAT starting to the first report of one of the following events: disease progression before surgery (any evidence of in situ contralateral disease was not be identified as progressive disease), disease recurrence (local, regional, distant, or contralateral) after surgery, or death from any cause.

Assessment of disease progression or recurrence events was performed using a combination of imaging and laboratory tests. Imaging surveillance included: (I) breast ultrasound and/or mammography: for evaluation of ipsilateral and contralateral breast; (II) chest computed tomography (CT): for detection of pulmonary and mediastinal recurrence; (III) abdominal ultrasound or CT: for assessment of liver metastasis and abdominal involvement; (IV) bone scan: performed only when clinically indicated (e.g., unexplained bone pain or elevated alkaline phosphatase); (V) magnetic resonance imaging (MRI) or positron emission tomography-computed tomography (PET‑CT): used at the discretion of the attending physician when routine imaging findings were equivocal or suspicious for recurrence. Laboratory assessment included routine blood tests (complete blood count, liver and renal function tests) and tumor markers [CA15‑3 and carcinoembryonic antigen (CEA)]. When feasible, suspected recurrence was confirmed by core needle biopsy or fine‑needle aspiration cytology. In the absence of pathological confirmation, recurrence was diagnosed based on unequivocal imaging findings (e.g., new or progressive lesions on CT, MRI, or PET‑CT) in conjunction with multidisciplinary review by at least two experienced clinicians. All imaging and pathology reports were independently reviewed by two investigators; any disagreement was resolved by consensus or adjudication by a third investigator.

Follow-up data were obtained through a combination of inpatient or outpatient medical records and telephone interviews. Information collected included survival status, dates and sites of recurrence or metastasis, date of death, and cause of death.

Statistical analysis

We first assessed the pattern of missing data. The proportion of missing values for each variable was less than 20%, and based on clinical knowledge, the data were assumed to be missing at random (MAR). To minimize information loss and control for potential bias, we performed multiple imputation for handling missing data. Baseline characteristics were summarized using descriptive statistics. Continuous variables were first tested for normality using the Shapiro-Wilk test. Normally distributed data were summarized by mean ± standard deviation (x¯±s); non-normally distributed data were summarized by median with interquartile range (IQR) [M (Q₁, Q₃)]. Whereas categorical variables were summarized by frequencies and percentages, and group differences were evaluated using the chi-square test or Fisher’s exact test.

A total of 253 and 174 patients received TCbHP and THP regimens, respectively. To minimize confounding, we performed 1:1 propensity-score matching (PSM). Propensity scores were estimated via logistic regression using age, menopausal status, HR status, HER2 status, clinical T stage, lymph node status, Ki-67 expression and Taxane. Nearest-neighbor matching without replacement was applied with a caliper of 0.05. Standardized mean differences (SMD) assessed pre- and post-match balance; an SMD <0.10 indicated good balance, and a Love plot was generated for visual inspection. After matching, 148 patient pairs were included in the final analysis.

In the matched cohort, the relationship between neoadjuvant regimen (TCbHP vs. THP) and pCR was examined using univariate and multivariate logistic regression with robust standard errors clustered on the matched-pair identifier; odds ratios (ORs) and 95% CIs were reported. Further pre-specified subgroup analyses were conducted to explore potential beneficiary populations of TCbHP, stratified by age, menopausal status, clinical T stage, lymph node status, HR status, HER2 status, Ki-67 expression and Taxane. Results were displayed as forest plots.

The median follow-up and its 95% CI were estimated by the reverse Kaplan-Meier method. DFS and EFS curves were constructed, and 3-year event rates were estimated using the Kaplan-Meier method. Between-group differences were evaluated using the log-rank test; HRs and 95% CIs were obtained from Cox proportional-hazards models with robust standard errors clustered on the matched-pair identifier, which were likewise applied in all subgroup analyses. All tests were two-sided, and P<0.05 was considered statistically significant. All analyses were conducted with R (version 4.4.3).

Results

Patient characteristics

Between January 2019 and December 2022, a total of 1,468 patients with newly diagnosed HER2-positive invasive breast cancer received NAT at our institution. After applying the predefined inclusion and exclusion criteria, 427 patients were ultimately included: 253 received the TCbHP regimen, and 174 received the THP regimen (Figure 1). Data were complete for all patients, and there was no loss to follow-up. The median ages were 48 years (IQR, 40–55 years) and 52 years (IQR, 44–60 years), respectively. Across the entire cohort, 220 patients (51.5%) were aged ≤50 years, 73 (17.1%) were aged >60 years, 298 (69.8%) were clinically stage T1–2, 348 (81.5%) had lymph node metastasis, 363 (85.0%) exhibited HER2 immunohistochemistry 3+, 226 (52.9%) were HR-positive, and 323 (75.6%) demonstrated Ki-67 >30%. Docetaxel was the most frequently used taxane, administered in 299 patients (70.0%), followed by nab‑paclitaxel in 107 (25.1%) and paclitaxel in 21 (4.9%). Baseline characteristic comparisons indicated statistically significant differences between the two groups in age, menstrual status, HR status and the types of taxanes used (Table 1).

Figure 1 Flowchart of patient enrollment. HER2, human epidermal growth factor receptor 2; TCbHP, taxane + carboplatin + trastuzumab + pertuzumab; THP, taxane + trastuzumab + pertuzumab.

To minimize potential confounding bias, 1:1 PSM was performed, yielding 148 matched pairs. After matching, the baseline characteristics of the two groups are shown in Table 2, and the standardized mean differences (SMD) for all variables were less than 0.1, indicating good balance. A Love plot was further constructed to visualize variable balance before and after PSM (Figure 2).

Figure 2 Standardized mean differences of variables before and after PSM. HER2, human epidermal growth factor receptor 2; HR, hormone receptor; PSM, propensity score matching; T, clinical T stage.

Efficacy evaluation

Among the overall cohort of 296 patients, 143 (48.3%) achieved pCR. The pCR rates were 53.4% (79/148) with TCbHP and 43.2% (64/148) with THP, yielding a borderline significant difference (OR =0.67; 95% CI: 0.42–1.05; P=0.08). Subgroup analyses showed higher pCR rates with TCbHP in most subgroups, except in the subgroups of patients aged >60 years, HER2 2+/FISH(+), and Ki-67 ≤30%. Statistically significant advantages were observed for TCbHP in patients aged ≤60 years (OR =0.56; 95% CI: 0.33–0.93; P=0.03), premenopausal status (OR =0.47; 95% CI: 0.24–0.91; P=0.03), and Ki-67 >30% (OR =0.48; 95% CI: 0.28–0.82; P=0.007). A borderline significant benefit trend was also noted in HR-negative patients (OR =0.53; 95% CI: 0.28–1.00; P=0.051). Formal interaction tests revealed a statistically significant interaction only between the two Ki-67 subgroups (P for interaction =0.02), indicating that the pCR benefit of TCbHP over THP may depend on Ki-67 expression levels, with greater benefit observed in patients with high Ki-67 expression (Figure 3).

Figure 3 Forest plot of pCR rates comparing TCbHP versus THP in the overall population and subgroups. CI, confidence interval; FISH, fluorescence in situ hybridization; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; OR, odds ratio; pCR, pathological complete response; T, clinical T stage; TCbHP, taxane + carboplatin + trastuzumab + pertuzumab; THP, taxane + trastuzumab + pertuzumab.

Further multivariate logistic regression analysis showed that (Table 3), after adjusting for confounding factors, the neoadjuvant regimen (TCbHP vs. THP) was not significantly associated with pCR (OR =0.685; 95% CI: 0.418–1.117; P=0.15). HR‑positive status (OR =0.437; 95% CI: 0.260–0.728; P=0.002) and HER2 2+/FISH(+) status (OR =0.188; 95% CI: 0.067–0.455; P=0.005) were identified as independent negative predictors of pCR. In contrast, age, menopausal status, clinical T stage, lymph node status, Ki‑67 expression level, and the type of taxane used showed no significant independent association with pCR (all P>0.05).

Survival outcomes

At the final follow-up, the median follow-up for survivors was 55 months (95% CI: 53–58) in the TCbHP group and 53 months (95% CI: 50–54) in the THP group; no disease-progression events were recorded in either group. In the TCbHP group, 7 of 148 patients (4.7%) experienced an EFS event, 71% within 36 months. Median time to recurrence was 32 months (IQR, 23–36 months). Sites were brain (4, 57.1%), bone (1, 14.3%), muscle (1, 14.3%), and liver (1, 14.3%). In the THP group, 9 of 148 patients (6.1%) had an EFS event, 66.7% within 36 months. Median time to recurrence was 35 months (IQR, 27–41 months). Sites were bone (3, 33.3%), chest wall (2, 22.2%), liver (2, 22.2%), brain (1, 11.1%), and synchronous liver and bone (1, 11.1%). 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 (HR =1.26; 95% CI: 0.47–3.40; P=0.64) (Figure 4).

Figure 4 Kaplan-Meier curves of event-free survival between treatment groups (TCbHP versus THP). CI, confidence interval; HR, hazard ratio; TCbHP, taxane + carboplatin + trastuzumab + pertuzumab; THP, taxane + trastuzumab + pertuzumab.

Subgroup analyses across all predefined strata (age, menopausal status, HR status, HER2 status, clinical T stage, lymph node status, Ki-67 expression, Taxane and pCR) showed no statistically significant difference in EFS between the TCbHP and THP groups (Figure 5). Formal interaction tests confirmed that none of these baseline factors significantly modified the treatment effect on EFS (all interaction P>0.05).

Figure 5 Forest plot of event-free survival comparing TCbHP versus THP in the overall population and subgroup. CI, confidence interval; FISH, fluorescence in situ hybridization; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; NA, not available; T, clinical T stage; TCbHP, taxane + carboplatin + trastuzumab + pertuzumab; THP, taxane + trastuzumab + pertuzumab.

Further analysis examined the association between pCR and DFS. Among the 143 patients who achieved pCR, 6 (4.2%) experienced a DFS event, compared with 10 (6.5%) of the 153 patients without pCR. Although the pCR group showed a numerically lower recurrence risk (HR =0.65; 95% CI: 0.23–1.78), the difference did not achieve statistical significance (P=0.40) (Figure 6). Subgroup exploration did not show a statistically significant DFS benefit associated with pCR in any subgroup. The estimated HRs were 0.50 (95% CI: 0.10–2.42; P=0.39) in HR‑positive patients and 0.65 (95% CI: 0.16–2.61; P=0.55) in the TCbHP arm, compared with 0.96 (95% CI: 0.21–4.29; P=0.96) in HR‑negative patients and 0.66 (95% CI: 0.15–2.95; P=0.59) in the THP arm (Figures 7,8).

Figure 6 Kaplan-Meier curves of disease-free survival by pathological response (pCR versus non-pCR). CI, confidence interval; HR, hazard ratio; pCR, pathological complete response.

Figure 7 Kaplan-Meier curves of disease-free survival by pathological response (pCR versus non-pCR) in the TCbHP (A) and THP (B) treatment subgroups. CI, confidence interval; HR, hazard ratio; pCR, pathological complete response; TCbHP, taxane + carboplatin + trastuzumab + pertuzumab; THP, taxane + trastuzumab + pertuzumab.

Figure 8 Kaplan-Meier curves of disease-free survival by response (pCR versus non-pCR) in the hormone receptor-negative (A) and hormone receptor-positive (B) subgroup. CI, confidence interval; HR, hazard ratio; pCR, pathological complete response; TCbHP, taxane + carboplatin + trastuzumab + pertuzumab; THP, taxane + trastuzumab + pertuzumab.

Discussion

In this propensity score‑matched cohort of patients with HER2‑positive breast cancer, the neoadjuvant TCbHP regimen showed a numerically higher pCR rate than THP (53.4% vs. 43.2%), but the difference was not statistically significant (P=0.08). The 3‑year EFS rates also did not differ significantly between the two groups (96.6% vs. 96.0%; HR =1.26, P=0.64). These findings suggest that, in an unselected overall population, the addition of carboplatin does not confer a clear benefit in pCR or short‑term survival.

Our observations are generally consistent with the recently published prospective neoCARHP trial (14). That study showed that THP was non‑inferior to TCbHP in terms of pCR (64.1% vs. 65.9%; non‑inferiority P=0.009), and the incidence of grade ≥3 adverse events was significantly lower in the THP group (20.7% vs. 34.6%). Furthermore, the HELEN-006 trial (13) also demonstrated that weekly nab‑paclitaxel combined with dual anti‑HER2 therapy achieved a significantly higher pCR rate than the TCbHP regimen (63.4% vs. 48.6%; P=0.002). Similarly, a single‑center series by Wu et al. (20) recorded pCR rates of 66% versus 53% for TCbHP and THP, respectively (P=0.07). As a real‑world data supplement, our study preliminarily explores the feasibility of safely omitting carboplatin in selected patients. Meanwhile, we provided supplementary 3‑year EFS survival data, offering a preliminary real‑world reference for the survival outcomes of the neoCARHP trial that are still pending.

Although the overall pCR rate did not differ significantly, prespecified subgroup analyses suggested that the pCR benefit of the TCbHP regimen was most pronounced in women aged ≤60 years, premenopausal patients, and those with Ki‑67 >30%, with a borderline benefit also observed in HR‑negative patients. Interaction testing revealed a statistically significant difference between Ki‑67 subgroups, suggesting that high Ki67 expression may be a potential biomarker of carboplatin benefit. In contrast, interaction tests for age and menopausal status did not reach statistical significance, indicating that these factors may be confounders or effect modifiers with limited impact; prospective studies are needed for further validation. Biologically, younger (21), HR-negative (22), highly proliferative tumors display greater genomic instability and a higher prevalence of homologous-recombination repair (HRR) defects; carboplatin-induced DNA cross-links are poorly repaired in this context, leading to synthetic lethality (23-25). None of the corresponding interaction tests, however, reached statistical significance, so these observations remain exploratory and should not yet dictate practice.

Regarding survival analysis, no significant difference in EFS was observed between TCbHP and THP, either in the overall population or across all subgroups (including age, menopausal status, HR status, HER2 status, clinical T stage, lymph node status, Ki‑67, etc.). Due to the limited number of EFS events, the short‑term survival results of this study are primarily descriptive, and the Cox regression analysis comparing EFS between the two regimens serves only as supportive evidence. Furthermore, the impact of pCR status on DFS did not reach statistical significance in this study (HR =0.65, P=0.40). This finding can be partly attributed to the small number of events, the relatively short follow‑up duration, and the dilution effect of post‑neoadjuvant adjuvant intensification therapy on initial pCR differences in current HER2positive breast cancer management (15).

Although BRCA1/2 mutations are well-established predictive biomarkers of platinum sensitivity in triple-negative breast cancer (25), their predictive value in HER2-positive breast cancer has not been fully validated. Current clinical guidelines do not recommend routine germline BRCA1/2 testing for patients with HER2-positive breast cancer (26), and such testing is not covered by national medical insurance, thus requiring out-of-pocket payment. Furthermore, a recent study reported that only approximately 6.6% of patients with HER2-positive breast cancer carry BRCA1/2 mutations (27). Given that the vast majority of patients in our cohort did not undergo BRCA testing, BRCA status was not included in our analysis. Nevertheless, it is theoretically possible that a subset of patients carrying BRCA mutations might exhibit differential responses to carboplatin-based therapy. Therefore, future prospective studies incorporating BRCA status assessment are warranted to further validate our findings.

Due to the retrospective nature of the study, we did not collect structured safety data; nevertheless, the excess toxicity of platinum is well documented. In KRISTINE (11), TCbHP was associated with higher rates of any-grade and grade ≥3 adverse events than T-DM1 + pertuzumab, including grade ≥3 neutropenia (25%), diarrhoea (15%) and febrile neutropenia (15%). Direct comparisons of TCbHP versus THP report any-grade toxicity in 99% versus 86.7% and grade ≥3 toxicity in 49.5% versus 12%; the most frequent grade ≥3 toxicities were leucopenia and neutropenia (23.3% each), while nausea affected half of patients (50.5%) (20). Precision oncology aims to preserve efficacy while minimizing harm and protecting quality of life. Taken together with our efficacy results, these safety data suggest that older patients with HR-positive, HER2-positive tumours and low proliferative indices could reasonably opt for carboplatin-free THP, thereby avoiding substantial haematologic and gastrointestinal toxicity without meaningful loss of pCR or long-term disease control.

Several limitations should be acknowledged. First, the single‑centre, retrospective design inherently limits causal inference. Although PSM was employed to balance baseline characteristics, we recognize that PSM cannot fully eliminate selection bias inherent in retrospective studies and may introduce bias through data loss from unmatched cases. Residual selection bias and unmeasured confounding cannot be fully excluded. Accordingly, our findings should be considered hypothesis‑generating and warrant confirmation in prospective randomized trials. Second, the modest sample size, median follow‑up <5 years, and low event rate reduce statistical power to detect small but clinically relevant survival differences; prospective, multicentre, larger‑scale trials are required to validate our findings. Third, it is theoretically possible that a subset of patients carrying BRCA mutations might exhibit differential responses to carboplatin‑based chemotherapy; however, due to the retrospective nature of the study and economic constraints, BRCA status was not incorporated into our analysis. Finally, treatment‑related adverse events were not systematically captured; while published data allow indirect toxicity comparisons, the absence of direct safety information within this cohort may impair precise clinical decision‑making.

Conclusions

This study shows that, in the neoadjuvant treatment of HER2-positive breast cancer, TCbHP and THP do not differ significantly in either pCR rate or 3-year EFS. Exploratory subgroup analyses suggested that TCbHP was associated with a higher pCR rate than THP in patients aged ≤60 years, premenopausal patients, and those with Ki‑67 >30%. However, formal interaction testing indicated that only Ki‑67 expression level significantly modified the treatment effect on pCR (P for interaction =0.02). These findings are hypothesis‑generating and require validation in prospective studies.

Acknowledgments

We acknowledge with appreciation the substantive contributions of all listed investigators.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0111/rc

Data Sharing Statement: Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0111/dss

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0111/prf

Funding: This work was supported by a grant from the National Natural Science Foundation Cultivation Project of Tianjin Medical University Cancer Institute and Hospital (No. 230210).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0111/coif). Z.S. reports that this work was supported by a grant from the National Natural Science Foundation Cultivation Project of Tianjin Medical University Cancer Institute and Hospital (No. 230210). The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Medical Ethics Committee of Tianjin Medical University Cancer Institute and Hospital (No. bc20262149) and individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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