Editor's Note: The 2026 Xianghu Breast Cancer Treatment Frontiers Academic Conference was held in Hangzhou from October 9 to 11, focusing on emerging concepts in breast cancer treatment, the integration of cardio-oncology into clinical practice, and the comprehensive management of antibody–drug conjugates (ADCs). During the meeting, Oncology Frontier interviewed Professor Zhanhong Chen of Zhejiang Cancer Hospital. She discussed the overall design and highlights of the cardio-oncology session, explained the growing importance of cardio-oncology in comprehensive breast cancer care, and shared insights into the evolving role of ADCs in advanced HER2-positive breast cancer, principles for treatment sequencing, and strategies for assessing and managing the cardiac safety of anti-HER2 ADCs.
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Oncology Frontier: As the opening speaker and concluding expert for the cardio-oncology session, could you introduce its overall design and key highlights? Based on your clinical experience, why is cardio-oncology becoming increasingly important in the comprehensive management of breast cancer?
Professor Zhanhong Chen: First, the overall design of this session was guided by the principles of comprehensive care throughout the disease course and multidisciplinary team (MDT) collaboration. The program was structured into three clearly defined, progressive sections.
The first section focused on foundational knowledge and early screening. Topics ranged from consensus on the integrated management of cancer-related hypertension to advances in the early detection of myocardial injury, emphasizing the importance of early identification and intervention.
The second section addressed key clinical challenges. Particular attention was given to the prevention and management of radiation-induced cardiac injury and the cardiac toxicity associated with anti-HER2 therapies, an issue of considerable concern among clinicians.
The third section explored emerging developments and interdisciplinary research. Topics included the management of cardiovascular toxicity associated with CDK4/6 inhibitors in breast cancer and a preventive clinical study investigating cardiovascular toxicity associated with sequential anthracycline and trastuzumab treatment.
Overall, the cardio-oncology session covered the major cardiovascular safety concerns encountered in contemporary breast cancer treatment, spanning conventional chemotherapy, targeted therapy, endocrine therapy, and radiotherapy.
Why, then, is cardio-oncology becoming increasingly important in comprehensive breast cancer care? Based on my clinical experience, I believe there are three main reasons.
First, survival among patients with breast cancer has improved substantially. With advances in diagnosis and treatment, breast cancer is increasingly becoming a chronic disease. As clinicians, our goal is not only to help patients live longer but also to ensure that they enjoy a good quality of life. Cardiovascular disease is one of the leading causes of non-cancer-related death among breast cancer survivors. This often-overlooked threat must not be underestimated.
Second, the expanding range of treatment options has introduced new challenges. As highlighted during this meeting, breast cancer treatment has evolved from anthracyclines and anti-HER2 monoclonal antibodies to newer agents such as ADCs and CDK4/6 inhibitors. Although these therapies can substantially improve treatment outcomes, they may also cause cardiovascular toxicities, including hypertension, myocardial injury, and arrhythmias. Clinicians must therefore remain mindful of cardiovascular risks when selecting and prescribing treatments.
Third, interdisciplinary collaboration is essential. Oncologists cannot be expected to master every aspect of cardiovascular medicine. Close collaboration with cardiologists, imaging specialists, and other relevant disciplines is necessary to establish standardized cardiovascular protection strategies. That is why we incorporated extensive expert discussions into this session, bringing specialists together to address current clinical challenges.
I believe that cardiovascular risk assessment and management must begin early and continue throughout cancer treatment. Only then can we truly achieve comprehensive, lifelong health management for patients with breast cancer. This is precisely why we established the cardio-oncology session.
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Oncology Frontier: In the HER2-positive breast cancer session, you presented “Exploring ADC Therapy in Advanced HER2-Positive Breast Cancer.” With an expanding range of ADCs, including trastuzumab deruxtecan (T-DXd), trastuzumab emtansine (T-DM1), and domestically developed ADCs, patients now have more treatment options. How has the role of ADCs in first- and second-line treatment of advanced HER2-positive breast cancer evolved? What principles should guide treatment sequencing in clinical practice?
Professor Zhanhong Chen: This is a highly topical issue and a practical question that clinicians face every day. ADCs are indeed reshaping the treatment landscape of advanced HER2-positive breast cancer.
First, let me discuss how the treatment landscape has changed. Historically, the standard first-line regimen for advanced HER2-positive breast cancer was dual HER2 blockade with trastuzumab and pertuzumab combined with a taxane. T-DM1 was the principal second-line treatment.
Today, however, T-DXd has demonstrated impressive efficacy in the second-line setting and even earlier lines of treatment, while the emergence of domestically developed ADCs, such as RC48, has further expanded treatment options. Consequently, treatment selection is shifting from a primarily line-of-therapy-driven approach toward one increasingly guided by therapeutic targets and the specific properties of individual drugs.
T-DXd has become the new standard of care in the second-line setting, while several domestically developed ADCs provide additional options in later lines. At the same time, ADCs are challenging established first-line treatment strategies. Results from the DESTINY-Breast09 (DB-09) study, reported in 2025, showed that T-DXd plus pertuzumab successfully challenged the standard THP regimen, extending median progression-free survival (mPFS) in advanced HER2-positive breast cancer from approximately a year and a half to three and a half years. Other clinical studies are also exploring first-line combinations of ADCs with immunotherapy or other targeted agents.
These developments suggest that the boundaries between first- and second-line treatment may become increasingly blurred. Greater emphasis will be placed on identifying the optimal treatment sequence for each patient.
Second, I believe three principles should guide treatment sequencing.
1. Balance efficacy and safety to maximize the benefit–risk ratio. As a next-generation ADC, T-DXd offers clear improvements in efficacy through its mechanism of action and is generally well tolerated. One important safety concern is interstitial lung disease (ILD), most reported cases of which are low grade (Grade 1). With multidisciplinary collaboration, early recognition, standardized grading and management, and appropriate patient education, many cases can be managed effectively.
2. Consider biomarkers and mechanisms of resistance. We need to identify the patients most likely to benefit from each treatment. ADCs may also have a role in patients whose HER2 expression has decreased or been lost, depending on the specific drug and clinical context. Treatment sequencing must take into account resistance to previous therapies, such as trastuzumab and pertuzumab, as well as the emergence of new target-related mutations.
3. Account for drug accessibility and quality of life. Many ADCs require intravenous administration and can cause adverse effects. Treatment decisions should therefore consider patients’ financial circumstances, convenience of access to care, and tolerance of adverse effects such as alopecia, nausea, and vomiting. For older or frail patients, for example, we may favor an ADC with a more manageable adverse-effect profile and a convenient administration schedule, when clinically appropriate.
Overall, treatment sequencing for HER2-positive breast cancer is no longer simply a matter of following guidelines step by step. It requires individualized, precision-based management that integrates the mechanism of each drug, patient characteristics, and available clinical evidence. Oncologists must become as familiar with the specific properties and toxicity profiles of each ADC as they are with conventional chemotherapy agents.
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Oncology Frontier: Although ADCs offer substantial efficacy, adverse effects such as ILD, cardiotoxicity, and hematologic toxicity remain important concerns. Drawing on your experience in cardio-oncology, how should the cardiac safety of anti-HER2 ADCs be assessed and managed? Which patients require particularly close monitoring? How can oncologists work with cardiologists to establish more standardized cardioprotection strategies?
Professor Zhanhong Chen: This is a particularly important question and one of the key interdisciplinary topics discussed during our cardio-oncology session. ADCs are indeed a double-edged sword: they can deliver substantial therapeutic benefits, but their adverse effects cannot be overlooked.
Although the incidence of cardiotoxicity associated with ADCs may be lower than that associated with conventional anthracyclines, cardiac injury can be clinically silent and, in some cases, irreversible. We therefore need to pay particular attention to several issues.
First, how should the cardiac safety of anti-HER2 ADCs be assessed and managed?
We must establish a closed-loop management pathway encompassing baseline assessment, regular monitoring, and early intervention.
Before treatment, all patients scheduled to receive an ADC should undergo a baseline electrocardiogram (ECG), echocardiography to assess left ventricular ejection fraction (LVEF), and testing for cardiac injury biomarkers, such as troponin and B-type natriuretic peptide (BNP). Patients with pre-existing cardiovascular disease also require more detailed risk stratification.
During treatment, monitoring should not be limited to routine ECGs. I recommend repeating echocardiography and cardiac biomarker testing every two to three treatment cycles during the initial phase of therapy, with subsequent monitoring tailored to the patient’s risk profile and the specific treatment regimen. In particular, for patients receiving T-DXd, clinicians must remain alert to potential declines in cardiac function while also monitoring carefully for ILD.
Second, which patients require particularly close monitoring?
I believe four high-risk groups warrant special attention.
1. Patients with a history of cardiovascular disease. This includes those with hypertension, coronary artery disease, heart failure, or arrhythmias.
2. Patients previously treated with anthracyclines or thoracic radiotherapy. These treatments may already have compromised cardiac reserve, potentially increasing vulnerability to subsequent treatment-related cardiac injury.
3. Older patients. Cardiovascular compensatory capacity tends to decline with age, and older adults are more likely to have multiple underlying medical conditions.
4. Patients receiving combination therapy. When ADCs are combined with other drugs that may cause cardiotoxicity, such as certain antiangiogenic agents, cardiovascular risks may accumulate.
Third, how can oncologists and cardiologists work together to establish standardized cardioprotection strategies?
This is an area we have been actively promoting. I believe progress should be made on three levels.
1. Establish dedicated cardio-oncology MDT clinics. Cardiologists should be involved early, assessing cardiovascular risk before cancer treatment begins and developing individualized cardioprotection plans. Depending on the patient’s clinical circumstances, these may include angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), or beta-blockers.
2. Develop standardized referral pathways. If monitoring reveals elevated troponin levels or an absolute decline in LVEF of more than 10 percentage points, the oncology team should promptly initiate a cardiology consultation rather than waiting until the patient develops symptoms such as chest tightness or shortness of breath.
3. Conduct prospective clinical studies. Much of the current evidence on ADC-associated cardiotoxicity comes from retrospective studies. More prospective data are needed to identify high-risk patients accurately and optimize cardioprotection strategies.
Finally, I want to emphasize that oncologists and cardiologists should not work in isolation; they must work side by side. Our shared goal is to help patients with breast cancer not only live longer but also live better.
Professor Zhanhong Chen
