Editor's Note: On October 16–17, the 19th National Breast Cancer Conference and the 21st Shanghai International Breast Cancer Conference (SIBCS) were successfully held in Shanghai. Under the chairmanship of Professor Jian Zhang from Fudan University Shanghai Cancer Center, voting was completed on the adjuvant and advanced disease sections of the “2027 Updates to the Guidelines and Consensus on the Diagnosis and Treatment of Breast Cancer.” Against this background, Oncology Frontier invited Professor Jian Zhang to discuss controversial issues in adjuvant and advanced breast cancer treatment, considerations in sequencing first- and second-line therapies for HER2-positive advanced breast cancer, and potential changes in the 2027 Guidelines and Consensus on the Diagnosis and Treatment of Breast Cancer (the “Little Red Book” guidelines).Oncology Frontier: As the expert guiding the voting process for the adjuvant and advanced disease sections of the “2027 Updates to the Guidelines and Consensus on the Diagnosis and Treatment of Breast Cancer,” which controversies in the current treatment of adjuvant and advanced breast cancer do you believe most urgently require a nationwide expert vote to build consensus? How would you determine the priority of these issues?
Professor Jian Zhang: During this voting process, I was primarily responsible for the adjuvant and advanced disease sections, which included more than 20 questions concerning the treatment of patients in these settings.
For patients with HR+/HER2− advanced breast cancer, the first issue to clarify is: now that CDK4/6 inhibitors have become the standard of care in the first-line setting, what are the most important factors to consider when selecting a CDK4/6 inhibitor? These include drug efficacy, accessibility, adverse events, and safety. I believe that everyone considers these factors comprehensively, and the purpose of the vote is precisely to identify the most important considerations and provide a basis for clinical decision-making.
In addition, treatment selection increasingly needs to be guided by individual patient characteristics, such as the presence or absence of PIK3CA/AKT1/PTEN gene mutations and ESR1 mutations. The questions were designed primarily to assess whether experts make treatment decisions strictly on the basis of clinical trial evidence. For example, approximately 70% (69.1%) of patients enrolled in the CAPItello-291 study had previously received CDK4/6 inhibitors. The evidence from this study in CDK4/6 inhibitor-pretreated patients may be more robust than that from the INAVO120 study, in which only 1.2% of enrolled patients had previously received CDK4/6 inhibitors. Therefore, prior exposure to CDK4/6 inhibitors is actually a very important consideration in treatment decision-making. Through this vote, we hope to understand how experts nationwide approach treatment for patients previously treated with CDK4/6 inhibitors.
In the treatment of patients with triple-negative breast cancer (TNBC), we have observed an evolving treatment landscape. First, immunotherapy is attracting increasing attention. For patients who have previously received immunotherapy in the neoadjuvant or adjuvant setting, should immunotherapy be incorporated into subsequent-line treatment? How long should the treatment-free interval be? The voting results showed that six-month and 12-month intervals were the most frequently selected options, reflecting current clinical practice.
Second, an increasing number of TROP2 ADCs are entering first-line treatment for TNBC. This raises several questions about second-line treatment selection for patients whose disease has been previously treated: should ADCs be prioritized over chemotherapy? When selecting an ADC, should we prioritize switching to an ADC with a different payload or one with a different antibody? We also held votes on these related questions, and the results offer useful insights for patient treatment.
Furthermore, the DESTINY-Breast09 (DB-09) study has provided a better treatment option for first-line therapy in HER2-positive breast cancer. Given that T-DXd plus pertuzumab (P) was approved for first-line treatment only recently, can this regimen replace THP in the first-line setting? What recommendation level should it receive? In making this decision, should we comprehensively consider factors such as accessibility, adverse events, overall survival, and tumor burden? These are all important issues that deserve attention.
As in previous years, we also included questions on the treatment of patients with HER2-positive breast cancer and brain metastases, and invited experts to vote on them. We also discussed the management of patients with newly diagnosed leptomeningeal metastases. Finally, we considered the efficacy of traditional Chinese medicine and acupuncture in improving treatment-related symptoms such as nausea and vomiting. We hope to continue discussing these issues with our colleagues.
Oncology Frontier: In HER2-positive advanced breast cancer, the DESTINY-Breast09 (DB-09) study demonstrated the important value of T-DXd plus pertuzumab in the first-line setting, providing a new treatment option. With an increasingly diverse range of first-line options available, how would you approach the sequencing of first- and second-line treatment for patients with HER2-positive advanced breast cancer? What are the main factors guiding your stratification and treatment decisions?
Professor Jian Zhang: As we all know, the DB-09 study has profound clinical implications for patients with HER2-positive advanced breast cancer. Based on the study data, the T-DXd plus pertuzumab regimen was approved by the National Medical Products Administration (NMPA) approximately two months ago for first-line treatment of HER2-positive advanced breast cancer. I very much hope that it will be included in the national medical insurance system as soon as possible and become available in clinical practice.
Personally, I believe that T-DXd plus pertuzumab should be included among the first-line treatment options for patients with HER2-positive advanced breast cancer. On this basis, we need to identify which patients are more suitable for THP and which are more suitable for T-DXd plus pertuzumab.
First, for patients with low tumor burden, we hope to achieve a state of no evidence of disease (NED) following treatment. Second, for patients with high tumor burden, we hope to achieve a rapid response and a meaningful level of efficacy through induction treatment. For patients in the intermediate group, treatment selection may be more subjective and depend on individual clinical judgment.
Nevertheless, patients in the T-DXd plus pertuzumab arm of the DB-09 study achieved a PFS benefit, accompanied by a substantial improvement in response rate. We therefore recognize that this regimen deserves an established place in first-line treatment. Going forward, we must also pay attention to related toxicities, including gastrointestinal adverse reactions, to ensure that the drug is used appropriately and over the long term.
Oncology Frontier: Looking ahead to the 2027 updates to the Guidelines and Consensus on the Diagnosis and Treatment of Breast Cancer, do you believe the treatment stratification framework for HER2-positive advanced breast cancer needs to be adjusted? With the continuous emergence of domestically developed ADCs, how should the guidelines balance the principle of “using the best drugs first” against drug accessibility and health economics? What changes do you anticipate in the upcoming update?
Professor Jian Zhang: Guideline updates are driven by clinical research data. Recently, a substantial amount of clinical evidence has emerged in the field of HER2-positive breast cancer, including data from the DB-09 and PATINA studies, as well as studies of domestically developed ADCs such as trastuzumab rezetecan (SHR-A1811) and bodutuzumab (A166).
However, the publication of these data will not completely change the treatment stratification framework for HER2-positive advanced breast cancer. We will continue to classify patients according to whether their disease remains sensitive or has become resistant to trastuzumab.
More importantly, as ADCs are increasingly being used in earlier lines of treatment, selecting appropriate drugs for subsequent-line therapy will become a major issue. This was also one of the key topics discussed at the conference. We invite everyone to look forward to the relevant updates in the 2027 “Little Red Book” guidelines.
Professor Jian Zhang
