Whether anthracyclines are essential in the neoadjuvant chemotherapy of HER2-positive breast cancer remains a long-debated question. The BCIRG-006 study suggested that anthracycline-containing and anthracycline-free regimens yielded numerically comparable survival outcomes, while the anthracycline-free TCbH regimen demonstrated a lower incidence of congestive heart failure and cardiac dysfunction. However, direct head-to-head comparisons between the two strategies are still limited. At the recent 19th St. Gallen Breast Cancer Conference (SGBCC 2025), Prof. Zhaoqing Fan and colleagues of Beijing Cancer Hospital presented a multicenter retrospective study evaluating the efficacy and safety of dual-targeted neoadjuvant therapy with or without anthracyclines in HER2-positive breast cancer. Oncology Frontier invited Professor Fan to interpret the findings.

Oncology Frontier: At this year’s SGBCC, you presented a study on anthracycline-free neoadjuvant therapy in early-stage HER2-positive breast cancer. Could you summarize the study and its findings?

Prof. Zhaoqing Fan:In collaboration with Professor Tao Wang’s team from the Fifth Medical Center of the PLA General Hospital, we conducted a multicenter retrospective study comparing two neoadjuvant strategies in patients with HER2-positive breast cancer. The two treatment arms were:

• EC-T regimen: Epirubicin and cyclophosphamide followed by docetaxel, combined with trastuzumab and pertuzumab.
• TCb regimen: Docetaxel and carboplatin, also combined with trastuzumab and pertuzumab.

The primary endpoint was pathological complete response (pCR) rate; secondary endpoints included event-free survival (EFS) and safety.

A total of 499 patients were enrolled, with 60% receiving the anthracycline-containing EC-T regimen and 40% receiving the anthracycline-free TCb regimen. The pCR rates were comparable between the two groups: 60.7% in the EC-T group versus 63.7% in the TCb group (P = 0.519). Similarly, three-year EFS showed no significant difference (HR 0.665, 95% CI: 0.186–2.382; P = 0.53), with EFS rates of 98.6% and 98.4%, respectively.

In terms of safety, neutropenia was the most commonly observed adverse event. Notably, 11% of patients in the EC-T group experienced neutropenia despite prophylactic G-CSF use, compared with 31% in the TCb group, which did not use G-CSF prophylactically. Febrile neutropenia occurred in 2% of EC-T patients and 6.4% of TCb patients.

Oncology Frontier: What is the clinical relevance of this study, and do you foresee future prospective trials to validate the findings?

Prof. Zhaoqing Fan:The debate over whether to omit anthracyclines in HER2-positive breast cancer treatment is longstanding. The earlier BCIRG-006 trial randomized 3,222 patients into three groups: AC-T (control), AC-TH (anthracycline-containing), and TCbH (anthracycline-free). Although this trial did not directly compare AC-TH and TCbH, the 10-year data presented at the San Antonio Breast Cancer Symposium showed similar outcomes: 10-year disease-free survival (DFS) rates of 74.6% and 73%, and 10-year overall survival (OS) rates of 85.9% and 83.3%, respectively.

Because the study was not powered to directly compare these two arms, its results were not statistically validated and remain unpublished in peer-reviewed literature. Consequently, strong evidence supporting the anthracycline-free strategy is still lacking, which limits its application in clinical guidelines.

In the era of intensified HER2-targeted therapy, there is increasing pressure to reduce chemotherapy-related toxicity. However, prospective head-to-head trials comparing these regimens are unlikely to be conducted in the future. Therefore, real-world data, like our current study, become especially important. We plan to expand this effort into a large-scale real-world study to better evaluate the efficacy and safety of anthracycline-free regimens in dual-targeted settings.

Oncology Frontier: Based on your study and clinical experience, what potential strategies exist for anthracycline-free systemic treatment in early HER2-positive breast cancer?

Prof. Zhaoqing Fan:Our findings suggest that both treatment regimens EC-T and TCb yield comparable pCR and EFS outcomes, making them both viable options. Clinicians should individualize treatment plans based on patient-specific characteristics.

Although anthracyclines may cause cardiotoxicity, these adverse effects are typically manageable. That said, the relatively short follow-up period in our study remains a limitation, and longer-term data—especially on cardiac safety—are needed to fully evaluate these regimens.

Looking ahead, for patients with small tumors, anthracycline-free regimens can be considered, supported by studies such as APT, wPH, and TCH. Additionally, research is underway exploring the use of targeted therapies, antibody-drug conjugates (ADCs), and even endocrine therapy in triple-positive breast cancers to further reduce reliance on chemotherapy.

Furthermore, early predictors such as PET-CT imaging may help identify patients who could avoid chemotherapy altogether. In the future, gene expression profiling may also aid in predicting response to HER2-targeted therapies, thereby enabling more patients to safely receive tailored treatments while minimizing unnecessary toxicity.

About Prof. Zhaoqing Fan

• PhD, Associate Professor, Chief Physician, and Master’s Supervisor
• Deputy Director, Breast Cancer Prevention and Treatment Center, Peking University Cancer Hospital
• Standing Committee Member, Breast Cancer Committee, Chinese Anti-Cancer Association
• Standing Committee Member, Breast Surgery Committee, Chinese Medical Doctor Association
• Chair, Multidisciplinary Breast Cancer Treatment Group, Chinese Medical Education Association
• Standing Committee Member, Breast Disease Committee, China International Exchange and Promotive Association for Medical and Health Care
• Vice President, Beijing Anti-Cancer Association