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. 2025 Jul 22;6:21. doi: 10.21037/tbcr-25-34

Chinese expert consensus on clinical diagnosis and treatment of breast cancer targeting HER2

Jianbin Li 1, Yueping Liu 2, Shu Wang 3, Shusen Wang 4, Shaohua Zhang 1, Man Li 5, Jin Yang 6, Xueli Mo 7, Min Yan 8, Cuizhi Geng 2, Feng Jin 9, Yongmei Yin 10, Jiong Wu 11, Erwei Song 12,✉, Zefei Jiang 1,✉; Chinese Society of Clinical Oncology Breast Cancer Committee
PMCID: PMC12314674  PMID: 40756961

Abstract

Background

Human epidermal growth factor receptor 2 (HER2) is an important driver gene and prognostic indicator of breast cancer and also a key predictor of HER2-targeted therapies. Both the low expression and the positive expression of the HER2 protein are clinically significant for disease treatment and prognosis.

Methods

(I) Establishment of expert group: the expert group consists of experts from departments such as medical oncology, breast surgery, and pathology; (II) literature search: mainly conducted in English databases (such as PubMed, Embase, and Cochrane Library) with a search cutoff date of June 1, 2025; (III) assessment of evidence quality and recommendation strength: evidence quality and recommendation opinions are graded based on the evidence category and recommendation level of the Chinese Society of Clinical Oncology (CSCO) guidelines.

Results

The emerging anti-HER2 drugs have greatly changed the diagnosis and treatment modalities of breast cancer and dramatically improved the prognosis of patients with HER2 expression in breast cancer. To optimize the treatment, an update of expert consensus on breast cancer with HER2 expression was made to adjust the different recommendation levels from early stage to metastatic stage. In this consensus, we also talk about the importance of clinical research, real-world evidence, biosimilars and so on.

Conclusions

The overarching goal of this consensus is to deliver individualized treatment strategies that not only prolong survival but also enhance quality of life, ensuring HER2-positive breast cancer patients receive the most advanced, patient-centered care available.

Keywords: Human epidermal growth factor receptor 2 (HER2), breast cancer, consensus, low expression

Highlight box.

Key recommendations

• This consensus endorses human epidermal growth factor receptor 2 (HER2) testing standards aligned with international guidelines while emphasizing region-specific strategies: preferential use of domestically approved agents based on local accessibility, tailored regimens for resource-limited areas, and integrated real-world evidence from Chinese cohorts.

What was recommended and what is new?

• Building on existing evidence supporting trastuzumab deruxtecan (T-DXd) for HER2-positive/low expression, the consensus introduces refined recommendations for sequential therapy in heavily pretreated patients. New additions include guidance on balancing drug reimbursement policies with optimal care and prioritizing research gaps in Chinese populations.

What is the implication, and what should change now?

• These recommendations urge clinicians to individualize HER2-targeted therapy considering regional resource disparities and domestic drug availability. We highlight the need for enhanced liquid biopsy integration in monitoring and call for expanded real-world data collection to refine future guidelines, ensuring alignment with China’s epidemiological and healthcare landscape.

Introduction

Human epidermal growth factor receptor 2 (HER2) is an important driver gene and prognostic indicator in breast cancer. It is also a main predictive indicator for anti-HER2 drug therapy. Trastuzumab has changed the diagnosis and treatment model of breast cancer. It has improved the prognosis of patients with HER2-positive breast cancer and is an important breakthrough in targeted therapy for tumors. In recent years, the successful launch of anti-HER2 drugs such as monoclonal antibodies (trastuzumab and pertuzumab), tyrosine kinase inhibitors (TKIs), and antibody-drug conjugates (ADCs) has achieved remarkable results in anti-HER2 treatment for breast cancer.

However, due to the significant differences in research and medical insurance strategies of anti-HER2 drugs between China and foreign countries (1), there are also differences in clinical practice. To better regulate the clinical treatment of breast cancer with HER2 expression, the experts of the Chinese Society of Clinical Oncology Breast Cancer (CSCO BC) Committee has updated the consensus after expert discussions, takes the consensus published in 2023 (2), the newly published CSCO BC guidelines (3), and the recent research progress into account.

Methods

Professor Zefei Jiang, President-elect of the Chinese Society of Clinical Oncology (CSCO), took the lead in formulating an expert consensus on HER2 breast cancer. On the 20 February 2025, the consensus expert group held a meeting to define the consensus on the diagnosis and treatment of HER2 from the diagnosis, neoadjuvant, adjuvant, treatment after metastasis, low expression of HER2, biosimilars, and so on. Finally, the CSCO expert consensus on the diagnosis and treatment of HER2 was formed through discussion and summary of several online meetings.

Results and discussion

Standardization of HER2 testing

Anti-HER2 targeted therapy is now fundamental for treating HER2-positive breast cancer at all stages. Accurately detecting and assessing HER2 protein expression and gene amplification is critical for guiding treatment and predicting prognosis. HER2 testing should be routine for all primary invasive breast cancers. Given the spatiotemporal heterogeneity of HER2 expression, which can cause inconsistent results across different samples (e.g., core needle biopsies vs. surgical specimens, primary vs. metastatic lesions, pre- and post-neoadjuvant therapy), early breast cancer patients should have post-surgical HER2 testing. Whenever possible, recurrent and metastatic lesions should also be tested. Additionally, post-neoadjuvant therapy residual tumors should undergo HER2 retesting.

HER2 detection must be performed in a quality-assured pathology laboratory, using standardized immunohistochemistry (IHC) or in situ hybridization (ISH). Proper tissue sampling, timely fixation in 4% neutral formalin, and adherence to standard protocols are essential. For bone metastasis specimens, separate hard and soft tissue regions during processing. Hard bone tissue should be decalcified with EDTA to minimize impact on HER2 testing. HER2 positivity is defined as IHC 3+ and/or fluorescence in situ hybridization (FISH) positivity. For IHC 2+ results, ISH-based HER2 gene amplification testing is required. Current ISH methods include FISH, chromogenic ISH (CISH), and silver ISH (SISH). If IHC results are 1+ or 0, HER2 status is considered negative.

ISH can also determine HER2 positivity, with dual-probe ISH interpretation as follows: (I) HER2/CEP17 ratio ≥2.0 and average HER2 copies/cell ≥4.0 → HER2-positive. (II) HER2/CEP17 ratio <2.0 and average HER2 copies/cell <4.0 → HER2-negative. (III) HER2/CEP17 ratio <2.0 but average HER2 copies/cell ≥6.0 → increase cell count; if unchanged, report as FISH-positive. (IV) HER2/CEP17 ratio <2.0 and average HER2 copies/cell 4.0–5.9 → recount signals in ≥20 nuclei. If unchanged, note in the FISH report that IHC results are needed for HER2 status determination (IHC 3+ → positive; IHC 0, 1+, or 2+ → negative). (V) HER2/CEP17 ratio ≥2.0 but average HER2 copies/cell <4.0 → increase cell count; if unchanged, report as FISH-negative. Note in the report that there is insufficient evidence for the benefit of anti-HER2 therapy in these patients and more data are needed.

Given that patients with low or ultralow HER2 expression may benefit from novel ADCs, experts recommend clearly defining these subgroups. “HER2-low” is defined as IHC 1+ or IHC 2+/non-amplified by ISH. “HER2-ultralow” is defined as IHC 0 with ≤10% of invasive cancer cells showing weak, incomplete membranous staining. Reporting should specify “HER2 IHC 0 (with membranous staining)”. Due to the clinical significance of HER2 expression levels, it is recommended to include external staining controls with different gradients in each staining run, and facilities with the capability should include 0, 1+, 2+, and 3+ controls.

Neoadjuvant therapy for HER2-positive breast cancer

Trastuzumab-based regimens are now standard for early-stage HER2-positive breast cancer. Effective neoadjuvant therapy can lead to higher pathological complete response (pCR) rates, which correlates with improved disease-free survival (DFS) and overall survival (OS) for patients.

The NeoSphere study (4) showed that adding pertuzumab to trastuzumab and chemotherapy improves pCR rates. The PEONY study (5) validated these findings in Asian populations and confirmed the long-term efficacy of dual-targeted therapy with trastuzumab and pertuzumab in the adjuvant setting. The KRISTINE study (5) demonstrated the efficacy and safety of the TCbHP (docetaxel, carboplatin, trastuzumab, and pertuzumab) regimen in the neoadjuvant setting, establishing TCbHP as a standard neoadjuvant regimen for HER2-positive breast cancer.

Ongoing researches are exploring neoadjuvant therapy optimization. The HELEN-006 study (6) found that six cycles of weekly trastuzumab, pertuzumab, and albumin-bound paclitaxel offered higher pCR rates and better tolerability than the standard TCbHP regimen. The NeoCARHP study compared the differences between 6 cycles of THP (docetaxel, trastuzumab, and pertuzumab) and TCbHP treatment, and the results showed that the pCR rate in the THP group was 64.1%, while that in the TCbHP group was 65.9% (P=0.0089). For patients unsuitable for platinum-containing regimens (e.g., those aged >60, with small tumor burden, or poor general condition), real-world studies suggest (7) six cycles of THP therapy can also achieve similar pCR rates compared to TCHP.

Apart from pertuzumab, the PHEDRA study (8) investigated the addition of pyrotinib, the Chinese-developed TKIs, to TH (docetaxel and trastuzumab) therapy, would achieve a total pCR rate of 41% (vs. 22% in the control group). Several ADCs are also showing promise outcomes in neoadjuvant settings. The FASCINATE-N study (9) demonstrated that the ADC SHR-A1811 monotherapy achieved a 63.2% pCR rate when compared with TCHP. The Destiny-Breast 11 study has explored the application of trastuzumab deruxtecan (T-DXd) in neoadjuvant therapy. Positive outcomes from this trial are anticipated to influence clinical practice.

Researchers are also exploring treatment strategies to improve pCR rates without these new targeted drugs. The PHERGain study (10) investigated de-escalating chemotherapy on neoadjuvant therapy response. After two cycles of dual-targeted therapy (trastuzumab and pertuzumab) with or without endocrine therapy, patients with response on positron emission tomography (PET) imaging continued the same regimen for six cycles, while non-responders switched to chemotherapy. The 3-year invasive DFS (iDFS) rate was 94.8% in the no-chemotherapy group, suggesting that chemo-free is feasible in some patients with early-stage HER2-positive breast cancer. The NeoPaTHer (11) study also showed that for patients with no response to two cycles of chemotherapy combined with trastuzumab, adding pyrotinib would increase the pCR rate by 1.9 times, providing more data on TKI use in neoadjuvant therapy.

After neoadjuvant therapy, subsequent adjuvant targeted therapy should be determined based on postoperative pathology. The KATHERINE study (12,13) showed that for patients without pCR, adjuvant trastuzumab emtansine (T-DM1) improved iDFS and OS compared to trastuzumab, regardless of prior neoadjuvant dual- or single-targeted therapy. However, the proportion of patients receiving dual-targeted treatment in neoadjuvant therapy was low in this study, and there is also a lack of head-to head data on T-DM1 versus HP (trastuzumab and pertuzumab) in adjuvant therapy. Both HP and T-DM1 are favorable. Besides, the ExteNET study (14) showed that one year of neratinib adjuvant therapy within two years after trastuzumab improved DFS. Although data on neratinib after HP is limited, the intensive therapy of neratinib is considerable.

Recommendations

  1. For neoadjuvant therapy in HER2-positive breast cancer, regimens containing trastuzumab and pertuzumab are preferred. Six cycles of the TCbHP regimen are recommended. For patients aged >60 years, with low tumor burden, or unable to tolerate platinum-based regimens, six cycles of THP therapy could be considered. The clinical feasibility of a four-cycle THP regimen followed by surgery and three cycles of adjuvant chemotherapy is controversial and is inferiorly recommended. Additionally, there is a limited acceptance level among experts for the AC-THP regimen (sequential anthracycline and taxane with dual-targeted therapy).

  2. Data on the comparison of TKI and pertuzumab with trastuzumab in the neoadjuvant setting are lacking. Experts recommend HP as the preferred recommendation for neoadjuvant therapy. Trastuzumab with pyrotinib is also an option based on domestically approved indications. However, postoperative adjuvant targeted therapy strategies for patients who respond to pyrotinib in the neoadjuvant setting remain controversial. Experts suggest referring to the use of HP for adjuvant therapy.

  3. The use of novel ADCs in neoadjuvant therapy for HER2-positive breast cancer is still under investigation. Patients are encouraged to participate in relevant clinical trials.

  4. After neoadjuvant therapy, adjuvant treatment strategies should be determined based on the neoadjuvant regimen and postoperative pathology:

    • ❖ For patients achieving pCR, dual-targeted therapy is generally recommended by Chinese experts, regardless of whether dual-targeted therapy or trastuzumab alone was used preoperatively.

    • ❖ For patients achieving non-pCR, if preoperative anti-HER2 therapy was trastuzumab alone, adjuvant T-DM1 is recommended, while dual-targeted therapy can be considered alternatively. If dual-targeted treatment is used in neoadjuvant setting, both T-DM1 or dual-targeted therapy could be used in adjuvant therapy. For patients who received HP in adjuvant therapy, intensive therapy with neratinib may be considered. However, due to a lack of data, the expert group does not routinely recommend neratinib therapy for patients who received T-DM1.

Adjuvant therapy for HER2-positive breast cancer

In early-stage HER2-positive breast cancer, adjuvant therapy with trastuzumab significantly reduces recurrence and mortality risks. The APHINITY trial (15) showed that in high-risk patients, adding pertuzumab to trastuzumab boosts iDFS, with greater benefits in node-positive subgroups. The ExteNET trial indicated that neratinib therapy for one year after trastuzumab adjuvant therapy improves iDFS in patients with stage II to III. For low-risk patients, the APT study (16) demonstrated that the weekly TH regimen achieves a 3-year iDFS of 98.7% and a 10-year iDFS of 91.3% (17).

Recommendations

  1. For patients with lymph node-positive, adjuvant pertuzumab and trastuzumab with chemotherapy such as AC-THP or TCbHP is recommended.

  2. For patients with lymph node negative while with risk factors [e.g., tumor >2 cm, hormone receptor (HR)-negative, high Ki67 index], trastuzumab with chemotherapy (AC-TH or TCbH) is recommended. THP is considered for some patients who are intolerant to combined chemotherapy.

  3. For low-risk patients (lymph node-negative and tumor ≤2 cm), TC + H (docetaxel + cyclophosphamide + trastuzumab) or weekly TH is recommended. THP adjuvant therapy is also an option when taking the good accessibility and tolerance of HP in China into account.

  4. For patients with hormone receptor-positive breast cancer who are unable to receive chemotherapy, trastuzumab plus endocrine therapy is a viable option.

  5. Experts agree that dual-targeted therapy is the first choice for lymph node-positive patients. High-risk patients can also receive neratinib therapy after 1 year of standard targeted treatment.

Treatment for HER2-positive metastatic breast cancer

HER2-targeted therapies offer significant benefits for patients with recurrent/metastatic or de novo stage IV HER2-positive breast cancer. The choice of treatment depends on prior therapies, hormone receptor status, and physical condition. Patients can be categorized into three groups: those who are sensitive to trastuzumab, those who have failed trastuzumab treatment, and those who have failed TKI treatment.

Trastuzumab-sensitive

The CLEOPATRA study (18) showed that docetaxel with trastuzumab and pertuzumab significantly extended progression-free survival (PFS) and OS compared to docetaxel with trastuzumab alone. The PHILA study (19) confirmed that trastuzumab, pyrotinib, and docetaxel markedly prolonged PFS in first-line compared to TH alone, with a median PFS of 24.3 vs. 10.4 months for TH therapy. Subgroup analysis of PHILA indicated that patients previously treated with (neo)adjuvant trastuzumab derived greater benefit from pyrotinib. Besides, the Destiny Breast 09 study compared the efficacy of T-DXd with the combination of T-DXd and pertuzumab or TH + pertuzumab. The results suggest that the median PFS of T-DXd combined with pertuzumab is 40.7 months, while the THP is 26.9 months [hazard ratio (HR) =0.56, 95% confidence interval (CI): 0.44–0.71]. Preliminary OS data suggest a trend favoring T-DXd plus pertuzumab (HR =0.84, 95% CI: 0.59–1.19; maturity 16.4%).

Failure to trastuzumab-based therapy

The DESTINY-Breast03 study (20,21) demonstrated that T-DXd significantly improved PFS and OS after trastuzumab, with a median PFS of 29.0 months and OS of 52.6 months, establishing T-DXd as a key treatment option. The PHENIX study (22) showed that pyrotinib plus capecitabine extended PFS and OS compared to capecitabine alone, with a median OS of 34.9 vs. 23.6 months. The PHOEBE study (23) also found that pyrotinib plus capecitabine outperformed lapatinib with capecitabine in PFS and OS. The EMILIA study (24) confirmed that T-DM1 monotherapy was superior to lapatinib with capecitabine. The NALA study (25) showed that neratinib plus capecitabine prolonged PFS in patients who had received ≥2 prior targeted therapies. The SOPHIA study (26) showed that margetuximab plus chemotherapy extended median OS by 1.8 months compared to trastuzumab plus chemotherapy. The HER2CLIMB study (27) demonstrated that tucatinib plus trastuzumab and capecitabine significantly prolonged PFS and OS, especially in patients with brain metastases. Unfortunately, the poor accessibility of margetuximab, tucatinib and the non-reimbursement policy of neratinib limited the further promotion of these drugs in China.

Failure to TKI-based therapy

Based on the results of Destiny Breast 03 study, T-DXd can be preferred after TKI. Although 16% of the population with TKI treatment failure was included in the DB-03 study, there were few patients received pyrotinib, which is different from the current situation in China. We have explored drug sequences for patients after trastuzumab and pyrotinib through several real-world researches (RWRs) (28,29), and confirmed that T-DXd is the optimal choice. Other options include HP dual-targeted therapy, T-DM1, or other anti-HER2 drugs.

Treatment choice is still a clinical challenge for patients after ADCs. For patients with T-DM1, T-DXd is definitely preferred. There is a lack of high-quality clinical data for patients after T-DXd. Treatment should be individualized based on prior therapies, considering previously effective HER2-targeted therapies or unused similar drugs, while assessing the feasibility of local therapy to maintain quality of life is also needed.

Patients with hormone receptor-positive/HER2-positive breast cancer

The SYSUCC-002 study (30) showed that trastuzumab plus endocrine therapy was non-inferior to trastuzumab plus chemotherapy, with fewer toxicities. The PATINA study (31) also showed that trastuzumab, pertuzumab therapy plus palbociclib and endocrine therapy could provide significant PFS benefits.

HER2-positive brain metastases

The DESTINY-Breast12 study (32) showed that T-DXd benefited patients with active or stable HER2-positive brain metastases, achieving a central nervous system (CNS) objective response rate (ORR) of 71.7%. The PERMEATE study (33,34) showed that pyrotinib plus capecitabine achieved a CNS ORR of 74.6% in untreated brain metastasis patients, with a median OS of 35.9 months, and 42.1% ORR in patients who have received irradiations. The BROPTIMA study (35) showed that a combination of pyrotinib and brain radiotherapy achieved a 1-year CNS-PFS rate of 74.9%, CNS-ORR of 85%, and median CNS-PFS of 18 months. This suggests that combining radiotherapy with pyrotinib is effective for HER2-positive advanced breast cancer with brain metastases.

Recommendations

  1. Patients with HER2-positive metastatic breast cancer should be fully informed about the efficacy and necessity of timely, rational anti-HER2-targeted therapy. Treatment should be stratified based on prior targeted therapy. Trastuzumab-sensitive populations are defined as: (i) trastuzumab-naïve; (ii) showing response to neoadjuvant therapy; (iii) having recurrence 1 year after the end of adjuvant therapy.

  2. For patients who are regarded as trastuzumab-sensitive, TH-based regimens are preferred. Both TH with pyrotinib and pertuzumab are viable options. Pyrotinib, a Chinese-developed targeted drug, shows significant PFS benefits, especially in patients previously treated with trastuzumab, aligning with current clinical practice in China. However, TH with pertuzumab has more clinical data. With the recent approval and insurance coverage of subcutaneous (SC) formulations of trastuzumab and pertuzumab in China, accessibility and convenience of TH + pertuzumab have been improved. Under these circumstances, both pertuzumab and pyrotinib are now superiorly recommended in Chinese guidelines. The regimens should be selected based on individual patient factors, such as drug availability and tolerability. Experts recognize the positive results of the ADCs in the first-line setting for HER2-positive cases, and T-DXd combined with pertuzumab may become a new standard first-line treatment in the future.

  3. For patients failed to trastuzumab, both T-DXd and pyrotinib are preferred options. Patient’s physical condition and prior adverse reactions should be considered during the treatment selection.

  4. For patients with TKI failure, there is no standard regimen. Experts recommend T-DXd as the preferred choice. For those patients with pertuzumab-naïve, HP plus chemotherapy can be considered. Switching to T-DM1 or other unused anti-HER2 drugs is also a considerable option. Participation in clinical trials is encouraged.

  5. In HER2-positive/HR-positive recurrent/metastatic breast cancer, anti-HER2 therapy with chemotherapy is recommended. For patients unsuitable for chemotherapy or with slow-progressing disease, anti-HER2 therapy with endocrine therapy and Cyclin D kinase (CDK) 4/6 inhibitors can be considered.

  6. The treatment of HER2-positive breast cancer with brain metastases should adhere to the basic principles of guidelines and multidisciplinary team discussions. Priority should be given to local treatments such as surgery and radiotherapy. For patients with asymptomatic brain metastases, progressive extracranial lesions, or progression after intracranial radiotherapy, drug therapy may be considered. For drug therapy, T-DXd or pyrotinib is preferred, and combination of drugs with radiotherapy may be considered if necessary.

HER2 low/ultra-low expression: a special case

The DESTINY-Breast04 trial (36) enrolled patients with HER2 low expression who had 1–2 lines of prior chemotherapy. At least one line of endocrine therapy is allowed for patients with HR-positive breast cancer. the result showed that T-DXd significantly improved PFS and OS compared to physician’s choice of chemotherapy. The PFS was 9.9 months for T-DXd vs. 5.1 months for chemotherapy, and OS was 23.4 vs. 16.8 months. T-DXd could reduce the risks of disease progression or death by 50% and 36%, respectively.

In DESTINY-Breast06 study (37), patients with HER2-low/ultra-low expression and HR-positive advanced breast cancer who had at least one line of prior endocrine therapy were enrolled. Compared to physician’s choice of chemotherapy (capecitabine, albumin-bound paclitaxel, or paclitaxel), T-DXd could significantly prolong PFS and increase ORR. Overall, the PFS was 13.2 months for T-DXd vs. 8.1 months for chemotherapy, and ORR was 57.3% vs. 31.2%, respectively.

Furthermore, some emerging anti-HER2 ADCs are also showing promising outcomes. A phase Ⅰ trial (38) assessed SHR-A1811 in patients with HER2-expressed/mutated, irresectable, late-stage, or metastatic solid tumors refractory to standard therapy. The result showed that SHR-A1811 led to objective responses in 59.9% (184/307) of all patients, 76.3% (90/118) of HER2-positive breast cancer, 60.4% (55/91) of HER2 low-expressing breast cancer. Another phase II trial (9) exploring SHR-A1811 in neoadjuvant therapy showed pCR rates of 63.2% for SHR-A1811 monotherapy and 62.5% for SHR-A1811 plus pyrotinib, similar to the 64.4% pCR rate of the TCbHP regimen. The SHR-A1811 exhibits acceptable tolerability, promising antitumor activity, and a favorable pharmacokinetic profile in breast cancer with HER2 expression

Recommendations

  1. For HR positive HER2 low/ultra-low patients, endocrine therapy with CDK4/6 inhibitors is chosen as first-line therapy. After that, T-DXd is recommended. Other options include sacituzumab govitecan or sacituzumab tirumotecan.

  2. For HR negative HER2 low/ultra-low patients, chemotherapy with or without immunotherapy is preferred as first-line therapy. After that, ADC drugs such as sacituzumab govitecan, T-DXd, or sacituzumab tirumotecan can be selected.

Randomized clinical study and RWR

Randomized clinical trials (RCTs) are indispensable for advancing cancer therapeutics. These studies not only provide patients with access to cutting-edge therapies but also facilitate the optimization of existing treatment protocols. Engagement in clinical research offers patients multifaceted benefits, including early access to innovative treatments, stringent monitoring of safety and efficacy profiles, and the opportunity for personalized treatment strategies tailored to their unique disease characteristics. Beyond individual patient care, such participation serves as a cornerstone of medical progress, driving the development of evidence-based practice and shaping future standards of care. Consequently, the expert panel strongly advocates for patient involvement—across all disease stages—in well-designed clinical trials.

RWR is equally critical for optimizing clinical practice in HER2-positive breast cancer. By analyzing data from actual clinical settings, RWR addresses limitations inherent in traditional clinical trials, such as narrow patient eligibility criteria. Unlike RCTs, which often focus on homogeneous populations, real-world studies encompass diverse patient demographics and track long-term outcomes, providing a more comprehensive understanding of treatment safety and effectiveness in routine care. This generates insights into the actual risk-benefit balance of therapies and informs healthcare resource allocation through health economic evaluations, ensuring treatments are both clinically effective and cost-efficient.

In China, HER2-positive breast cancer RWR faces distinct challenges, including inconsistent data standardization and substantial regional disparities in healthcare delivery. However, the country’s large patient population and diverse treatment practices present unique opportunities for generating robust, representative evidence. The expert group emphasizes the need for collaboration among clinicians, research institutions, and policymakers to translate real-world evidence into updated clinical guidelines and practice innovations, ultimately enhancing care for broader patient populations.

Biosimilars

Biosimilars are biological medicinal products that exhibit high similarity to an approved reference innovator drug in terms of quality, safety, and efficacy. These therapies undergo rigorous regulatory scrutiny and must be supported by comprehensive data from pharmacological, non-clinical, and clinical trials to demonstrate comparability to the reference product. Clinical evidence has shown that the trastuzumab biosimilar approved in China is clinically equivalent to the original trastuzumab, with comparable efficacy and safety profiles in real-world use.

In clinical practice, biosimilars are considered interchangeable with their reference drugs, offering equivalent therapeutic outcomes while addressing two critical healthcare challenges: improved drug accessibility and reduced treatment costs. By leveraging the established safety and efficacy of the reference product, biosimilars provide patients with reliable treatment options at a lower financial burden, particularly in regions where access to original biologics may be limited.

The expert group strongly advocates for patient involvement in well-designed clinical trials and real-world studies evaluating biosimilars (39). Such research not only reinforces the robustness of their safety and efficacy profiles but also contributes to the ongoing optimization of treatment strategies, ensuring these therapies continue to meet the needs of diverse patient populations.

New formulations of targeted drugs

In recent years, advancements in SC formulation technology—particularly the integration of recombinant human hyaluronidase—have driven the approval of several SC formulations of intravenous anti-tumor monoclonal antibodies. In breast cancer therapy, two notable SC formulations have been incorporated into China’s national medical insurance program: trastuzumab monotherapy and the trastuzumab-pertuzumab dual-target SC combination.

Landmark studies such as HannaH (40) and FeDeriCa studies (41) have confirmed that these SC formulations demonstrate non-inferior efficacy and comparable safety profiles to their intravenous counterparts, validating their clinical interchangeability. Key findings from these trials highlight consistent pharmacokinetic parameters, ORRs, and adverse event profiles between SC and intravenous administrations, solidifying their role in modern oncology practice.

In the context of adjuvant and maintenance therapies for HER2-positive breast cancer, SC formulations are poised to assume an increasingly pivotal role. Their adoption aligns with global trends toward patient-centered care, offering advantages such as reduced treatment time, improved convenience, and potential gains in treatment adherence—particularly for long-term maintenance settings. As healthcare systems prioritize efficiency and patient quality of life, the expansion of SC formulations represents a significant advancement in optimizing HER2-targeted therapy delivery.

Conclusions

In the precision medicine era, the diagnosis and management of HER2-positive breast cancer have undergone remarkable advancements. Innovations in HER2 detection technologies—coupled with standardized interpretation of IHC and ISH results—have established a robust foundation for tailored anti-HER2 therapy. Concurrently, the development of novel anti-HER2 agents and breakthroughs in clinical research have expanded treatment paradigms, offering patients a diverse array of evidence-based options.

The overarching goal of this consensus is to deliver individualized treatment strategies that not only prolong survival but also enhance quality of life, ensuring HER2-positive breast cancer patients receive the most advanced, patient-centered care available. This multidisciplinary approach embodies the spirit of precision medicine, where diagnostic accuracy and therapeutic innovation converge to drive better outcomes for patients.

Supplementary

The article’s supplementary files as

tbcr-06-21-coif.pdf (1.4MB, pdf)
DOI: 10.21037/tbcr-25-34

Acknowledgments

We acknowledge all the members who participated in the discussions.

Members of the expert panel (in alphabetical order): Chen Zhanhong (Zhejiang Provincial Cancer Hospital); Fan Zhimin (The First Hospital of Jilin University); Fu Peifen (The First Affiliated Hospital of Zhejiang University); Geng Cuizhi (The Fourth Hospital of Hebei Medical University); Jiang Hongchuan (Beijing Chaoyang Hospital Affiliated to Capital Medical University); Jiang Yizhou (Fudan University Shanghai Cancer Center); Jiang Zefei (Department of Oncology, The Fifth Medical Center of PLA General Hospital); Jin Feng (The First Affiliated Hospital of China Medical University); Li Hongyuan (The First Affiliated Hospital of Chongqing Medical University); Li Jianbin (The Fifth Medical Center of PLA General Hospital); Li Man (The Second Affiliated Hospital of Dalian Medical University); Li Xingrui (Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology); Liao Ning (Guangdong Provincial People’s Hospital); Liu Jian (Fujian Cancer Hospital); Liu Qiang (Sun Yat-sen Memorial Hospital of Sun Yat-sen University); Liu Yinhua (Peking University First Hospital); Liu Yueping (The Fourth Hospital of Hebei Medical University); Liu Yunjiang (The Fourth Hospital of Hebei Medical University); Liu Zhenzhen (Henan Cancer Hospital); Nie Jianyun (Yunnan Cancer Hospital); Ouyang Quchang (Hunan Cancer Hospital); Pan Yueyin (The First Affiliated Hospital of University of Science and Technology of China); Ren Guosheng (The First Affiliated Hospital of Chongqing Medical University); Shao Zhimin (Fudan University Shanghai Cancer Center); Song Erwei (Sun Yat-sen Memorial Hospital of Sun Yat-sen University); Sun Gang (Xinjiang Medical University Cancer Hospital); Sun Tao (Liaoning Cancer Hospital); Teng Yuee (The First Affiliated Hospital of China Medical University); Tong Zhongsheng (Tianjin Medical University Cancer Institute & Hospital); Wang Haibo (Affiliated Hospital of Qingdao University School of Medicine); Wang Jiandong (First Medical Center of PLA General Hospital); Wang Kun (Guangdong Provincial People’s Hospital); Wang Shu (Peking University People’s Hospital); Wang Shusen (Sun Yat-sen University Cancer Center); Wang Tao (The Fifth Medical Center of PLA General Hospital); Wang Xiang (Cancer Institute and Hospital, Chinese Academy of Medical Sciences); Wang Xiaojia (Zhejiang Provincial Cancer Hospital); Wang Xin (Cancer Institute and Hospital, Chinese Academy of Medical Sciences); Wu Jiong (Fudan University Shanghai Cancer Center); Xu Binghe (Cancer Institute and Hospital, Chinese Academy of Medical Sciences); Yan Min (Henan Cancer Hospital); Yan Ying (Beijing University Cancer Hospital); Yang Jin (The First Affiliated Hospital of Xi’an Jiaotong University); Yin Yongmei (Jiangsu Provincial People’s Hospital); Yu Keda (Fudan University Shanghai Cancer Center); Yu Zhigang (The Second Hospital of Shandong University); Yuan Peng (Cancer Institute and Hospital, Chinese Academy of Medical Sciences); Zhang Jianguo (The Second Affiliated Hospital of Harbin Medical University); Zhang Jin (Tianjin Medical University Cancer Institute & Hospital); Zhang Pin (Cancer Institute and Hospital, Chinese Academy of Medical Sciences); Zhang Qingyuan (Heilongjiang Cancer Hospital) and Zhang Shaohua (Department of Oncology, The Fifth Medical Center of PLA General Hospital).

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.

Footnotes

Funding: This work was supported by National Science and Technology Major Project (2024ZD0519805) and the National Natural Science Foundation of China (82404074).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tbcr.amegroups.com/article/view/10.21037/tbcr-25-34/coif). Z.J. serves as the Editor-in-Chief of Translational Breast Cancer Research. J.L. serves as the unpaid Managing Editor of Translational Breast Cancer Research. Y.L., Shu Wang serve as the unpaid editorial board members of Translational Breast Cancer Research from May 2025 to December 2027. Shusen Wang, C.G., F.J., Y.Y., J.W., and E.S. serve as the unpaid editorial board members of Translational Breast Cancer Research from March 2024 to February 2026. The other authors have no conflicts of interest to declare.

References

  • 1.Li J, Zhou J, Wang H, et al. Trends in Disparities and Transitions of Treatment in Patients With Early Breast Cancer in China and the US, 2011 to 2021. JAMA Netw Open 2023;6:e2321388. 10.1001/jamanetworkopen.2023.21388 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Li J, Wang X, Wang S, et al. Expert consensus on the clinical diagnosis and targeted therapy of HER2 breast cancer (2023 edition). Transl Breast Cancer Res 2022;3:30. 10.21037/tbcr-22-48 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Li J, Hao C, Wang K, et al. Chinese Society of Clinical Oncology (CSCO) Breast Cancer guidelines 2024. Transl Breast Cancer Res 2024;5:18. 10.21037/tbcr-24-31 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Gianni L, Pienkowski T, Im YH, et al. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol 2016;17:791-800. 10.1016/S1470-2045(16)00163-7 [DOI] [PubMed] [Google Scholar]
  • 5.Shao Z, Pang D, Yang H, et al. Efficacy, Safety, and Tolerability of Pertuzumab, Trastuzumab, and Docetaxel for Patients With Early or Locally Advanced ERBB2-Positive Breast Cancer in Asia: The PEONY Phase 3 Randomized Clinical Trial. JAMA Oncol 2020;6:e193692. 10.1001/jamaoncol.2019.3692 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Chen XC, Jiao DC, Qiao JH, et al. De-escalated neoadjuvant weekly nab-paclitaxel with trastuzumab and pertuzumab versus docetaxel, carboplatin, trastuzumab, and pertuzumab in patients with HER2-positive early breast cancer (HELEN-006): a multicentre, randomised, phase 3 trial. Lancet Oncol 2025;26:27-36. 10.1016/S1470-2045(24)00581-3 [DOI] [PubMed] [Google Scholar]
  • 7.Wu S, Bian L, Wang H, et al. De-escalation of neoadjuvant taxane and carboplatin therapy in HER2-positive breast cancer with dual HER2 blockade: a multicenter real-world experience in China. World J Surg Oncol 2024;22:214. 10.1186/s12957-024-03468-5 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Wu J, Jiang Z, Liu Z, et al. Neoadjuvant pyrotinib, trastuzumab, and docetaxel for HER2-positive breast cancer (PHEDRA): a double-blind, randomized phase 3 trial. BMC Med 2022;20:498. 10.1186/s12916-022-02708-3 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Li JJ, Wang ZH, Chen L, et al. Efficacy and safety of neoadjuvant SHR-A1811 with or without pyrotinib in women with locally advanced or early HER2-positive breast cancer: a randomized, open-label, phase II trial. Ann Oncol 2025;36:651-59. [DOI] [PubMed] [Google Scholar]
  • 10.Pérez-García JM, Cortés J, Ruiz-Borrego M, et al. 3-year invasive disease-free survival with chemotherapy de-escalation using an (18)F-FDG-PET-based, pathological complete response-adapted strategy in HER2-positive early breast cancer (PHERGain): a randomised, open-label, phase 2 trial. Lancet 2024;403:1649-59. 10.1016/S0140-6736(24)00054-0 [DOI] [PubMed] [Google Scholar]
  • 11.Wang F, Wang Y, Xiong B, et al. Neoadjuvant pyrotinib and trastuzumab in HER2-positive breast cancer with no early response (NeoPaTHer): efficacy, safety and biomarker analysis of a prospective, multicentre, response-adapted study. Signal Transduct Target Ther 2025;10:45. 10.1038/s41392-025-02138-6 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Geyer CE, Jr, Untch M, Huang CS, et al. Survival with Trastuzumab Emtansine in Residual HER2-Positive Breast Cancer. N Engl J Med 2025;392:249-57. 10.1056/NEJMoa2406070 [DOI] [PubMed] [Google Scholar]
  • 13.von Minckwitz G, Huang CS, Mano MS, et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med 2019;380:617-28. 10.1056/NEJMoa1814017 [DOI] [PubMed] [Google Scholar]
  • 14.Martin M, Holmes FA, Ejlertsen B, et al. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2017;18:1688-700. 10.1016/S1470-2045(17)30717-9 [DOI] [PubMed] [Google Scholar]
  • 15.Piccart M, Procter M, Fumagalli D, et al. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol 2021;39:1448-57. 10.1200/JCO.20.01204 [DOI] [PubMed] [Google Scholar]
  • 16.Tolaney SM, Guo H, Pernas S, et al. Seven-Year Follow-Up Analysis of Adjuvant Paclitaxel and Trastuzumab Trial for Node-Negative, Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer. J Clin Oncol 2019;37:1868-75. 10.1200/JCO.19.00066 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Tolaney SM, Tarantino P, Graham N, et al. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer: final 10-year analysis of the open-label, single-arm, phase 2 APT trial. Lancet Oncol 2023;24:273-85. 10.1016/S1470-2045(23)00051-7 [DOI] [PubMed] [Google Scholar]
  • 18.Swain SM, Miles D, Kim SB, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol 2020;21:519-30. 10.1016/S1470-2045(19)30863-0 [DOI] [PubMed] [Google Scholar]
  • 19.Ma F, Yan M, Li W, et al. Pyrotinib versus placebo in combination with trastuzumab and docetaxel as first line treatment in patients with HER2 positive metastatic breast cancer (PHILA): randomised, double blind, multicentre, phase 3 trial. BMJ 2023;383:e076065. 10.1136/bmj-2023-076065 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Cortés J, Kim SB, Chung WP, et al. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Engl J Med 2022;386:1143-54. 10.1056/NEJMoa2115022 [DOI] [PubMed] [Google Scholar]
  • 21.Cortés J, Hurvitz SA, Im SA, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer: long-term survival analysis of the DESTINY-Breast03 trial. Nat Med 2024;30:2208-15. 10.1038/s41591-024-03021-7 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Yan M, Bian L, Hu X, et al. Pyrotinib plus capecitabine for human epidermal growth factor receptor 2-positive metastatic breast cancer after trastuzumab and taxanes (PHENIX): a randomized, double-blind, placebo-controlled phase 3 study. Transl Breast Cancer Res 2020;1:13. [Google Scholar]
  • 23.Xu B, Yan M, Ma F, et al. Pyrotinib plus capecitabine versus lapatinib plus capecitabine for the treatment of HER2-positive metastatic breast cancer (PHOEBE): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet Oncol 2021;22:351-60. 10.1016/S1470-2045(20)30702-6 [DOI] [PubMed] [Google Scholar]
  • 24.Diéras V, Miles D, Verma S, et al. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol 2017;18:732-42. 10.1016/S1470-2045(17)30312-1 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Saura C, Oliveira M, Feng YH, et al. Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial. J Clin Oncol 2020;38:3138-49. 10.1200/JCO.20.00147 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Rugo HS, Im SA, Cardoso F, et al. Efficacy of Margetuximab vs Trastuzumab in Patients With Pretreated ERBB2-Positive Advanced Breast Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol 2021;7:573-84. 10.1001/jamaoncol.2020.7932 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Murthy RK, Loi S, Okines A, et al. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. N Engl J Med 2020;382:597-609. 10.1056/NEJMoa1914609 [DOI] [PubMed] [Google Scholar]
  • 28.Li F, Li J, Ji C, et al. Novel anti-HER2 ADCs vs dual anti-HER2 antibody for HER2-positive metastatic breast cancer failed to tyrosine kinase inhibitor. Oncologist 2025;30:oyae144. 10.1093/oncolo/oyae144 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Ji C, Li F, Yuan Y, et al. Novel Anti-HER2 Antibody-Drug Conjugates Versus T-DM1 for HER2-Positive Metastatic Breast Cancer After Tyrosine Kinase Inhibitors Treatment. Oncologist 2023;28:e859-66. 10.1093/oncolo/oyad127 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Hua X, Bi XW, Zhao JL, et al. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res 2022;28:637-45. 10.1158/1078-0432.CCR-21-3435 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Fournaise A, Lauridsen JT, Nissen SK, et al. Structured decision support to prevent hospitalisations of community-dwelling older adults in Denmark (PATINA): an open-label, stepped-wedge, cluster-randomised controlled trial. Lancet Healthy Longev 2023;4:e132-42. 10.1016/S2666-7568(23)00023-5 [DOI] [PubMed] [Google Scholar]
  • 32.Harbeck N, Ciruelos E, Jerusalem G, et al. Trastuzumab deruxtecan in HER2-positive advanced breast cancer with or without brain metastases: a phase 3b/4 trial. Nat Med 2024;30:3717-27. 10.1038/s41591-024-03261-7 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Yan M, Ouyang Q, Sun T, et al. Pyrotinib plus capecitabine for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases (PERMEATE): a multicentre, single-arm, two-cohort, phase 2 trial. Lancet Oncol 2022;23:353-61. 10.1016/S1470-2045(21)00716-6 [DOI] [PubMed] [Google Scholar]
  • 34.Yan M, Ouyang Q, Sun T, et al. Pyrotinib plus capecitabine for patients with HER2-positive metastatic breast cancer and brain metastases (PERMEATE trial): overall survival results from a multicenter, single-arm, two-cohort, phase 2 trial. EClinicalMedicine 2024;76:102837. 10.1016/j.eclinm.2024.102837 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Yang Z, Meng J, Mei X, et al. Brain Radiotherapy With Pyrotinib and Capecitabine in Patients With ERBB2-Positive Advanced Breast Cancer and Brain Metastases: A Nonrandomized Phase 2 Trial. JAMA Oncol 2024;10:335-41. 10.1001/jamaoncol.2023.5791 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Modi S, Jacot W, Yamashita T, et al. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med 2022;387:9-20. 10.1056/NEJMoa2203690 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Bardia A, Hu X, Dent R, et al. Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer. N Engl J Med 2024;391:2110-22. 10.1056/NEJMoa2407086 [DOI] [PubMed] [Google Scholar]
  • 38.Yao H, Yan M, Tong Z, et al. Safety, Efficacy, and Pharmacokinetics of SHR-A1811, a Human Epidermal Growth Factor Receptor 2-Directed Antibody-Drug Conjugate, in Human Epidermal Growth Factor Receptor 2-Expressing or Mutated Advanced Solid Tumors: A Global Phase I Trial. J Clin Oncol 2024;42:3453-65. 10.1200/JCO.23.02044 [DOI] [PubMed] [Google Scholar]
  • 39.Xu B, Zhang Q, Sun T, et al. Efficacy, Safety, and Immunogenicity of HLX02 Compared with Reference Trastuzumab in Patients with Recurrent or Metastatic HER2-Positive Breast Cancer: A Randomized Phase III Equivalence Trial. BioDrugs 2021;35:337-50. 10.1007/s40259-021-00475-w [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Ismael G, Hegg R, Muehlbauer S, et al. Subcutaneous versus intravenous administration of (neo)adjuvant trastuzumab in patients with HER2-positive, clinical stage I-III breast cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial. Lancet Oncol 2012;13:869-78. 10.1016/S1470-2045(12)70329-7 [DOI] [PubMed] [Google Scholar]
  • 41.Tan AR, Im SA, Mattar A, et al. Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection plus chemotherapy in HER2-positive early breast cancer (FeDeriCa): a randomised, open-label, multicentre, non-inferiority, phase 3 study. Lancet Oncol 2021;22:85-97. 10.1016/S1470-2045(20)30536-2 [DOI] [PubMed] [Google Scholar]

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    DOI: 10.21037/tbcr-25-34

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