Editorial Not：With the rapid advancement of medical technology, the treatment of HER2-positive breast cancer has entered a new chapter. In recent years, the emergence of anti-HER2 targeted drugs and new ADC (Antibody-Drug Conjugates) drugs has not only enriched the treatment options but also brought unprecedented hope to patients with HER2-positive breast cancer. At CSCO 2024, Oncology Frontier invited Dr. Yongmei Yin from Jiangsu Provincial Hospital to review the evolution of HER2-positive breast cancer medical treatment. From single-target therapy to dual-target treatment, and now into the era of TKI (Tyrosine Kinase Inhibitors) and ADC therapies, every step reflects the wisdom and efforts of the medical community. Professor Yin also commented on the remarkable efficacy of T-DXd in brain metastasis patients, as seen in the DB-12 study presented at the 2024 ESMO conference, and shared valuable insights on balancing efficacy and safety in clinical practice.

01 Oncology Frontier: In the treatment of HER2-positive breast cancer patients, we now see the widespread use of anti-HER2 targeted therapies and new ADC drugs. Could you review the history of medical treatment for HER2-positive breast cancer and explain how these drugs have changed the treatment landscape?

Dr. Yongmei Yin: Breast cancer treatment has entered an era of molecular classification and personalized therapy. For HER2-positive breast cancer, we have explored anti-HER2 therapies for more than 20 years, going from single-target treatment to dual-target therapy with trastuzumab, then to the TKI treatment era, and now, we have entered the ADC treatment era. Over the past few years, we have continuously explored this field, and new drugs have gradually entered clinical practice. As a result, whether in early-stage or late-stage treatment, the prognosis for HER2-positive breast cancer patients has improved significantly.

In the field of anti-HER2 therapy, many Chinese experts and scholars have made great contributions to the development of new drugs. For example, the small-molecule TKI drug pyrotinib, under the leadership of Academician Binghe Xu and Professor Zefei Jiang, has shown positive results in studies such as PHOEBE, PHENIX, and PHILA, establishing its position in second-line and first-line treatment of HER2-positive advanced breast cancer. Additionally, new ADC drugs, like SHR-A1811 developed in China, are being explored for their efficacy in treating HER2-positive advanced breast cancer. At this year’s conference, I also reported on a clinical trial involving the small-molecule HER2 inhibitor ST-1703 in treating HER2-positive advanced solid tumors, and I believe there will be more exciting developments for patients in the field of ADC treatments in the future.

02 Oncology Frontier: At the recently concluded 2024 ESMO conference, the main results of the DB-12 study were presented on the first day, and the findings were simultaneously published in Nature Medicine. In the DESTINY-Breast12 study, T-DXd demonstrated significant efficacy in HER2-positive metastatic breast cancer (mBC) patients with brain metastases. What direct impact do you think these findings will have on treatment strategies for HER2-positive mBC patients? Could you provide an overview and your commentary on the study?

Dr. Yongmei Yin: In recent years, many new drugs have been introduced in the field of anti-HER2 therapy, significantly improving the prognosis for patients with HER2-positive advanced breast cancer. Currently, the median overall survival for HER2-positive advanced breast cancer patients is close to five years. As the survival time for these patients has increased, the likelihood of brain metastasis has also risen.

HER2-positive breast cancer is prone to brain metastasis. Generally, about 50% of patients with HER2-positive advanced breast cancer will develop brain metastases, so treating these patients is critical. Over the past few years, small-molecule TKI drugs such as tucatinib, lapatinib, and pyrotinib have been explored in breast cancer patients with brain metastasis, and some positive results have been reported. Additionally, small sample studies have been conducted on T-DM1 in HER2-positive brain metastasis patients.

The results of the DB-12 study, presented at this year’s ESMO conference, refocused our attention on HER2-positive brain metastasis patients. The DB-12 study is currently the most highly anticipated and largest study focused on HER2-positive brain metastasis patients, and it has demonstrated the efficacy of T-DXd (DS-8201) in treating brain metastases. The results showed that the median progression-free survival (mPFS) in the brain metastasis cohort was 17.3 months, with a 12-month PFS rate of 61.6%. The objective response rate (ORR) in the non-brain metastasis cohort was 62.7%. I believe that with the publication of these results, our clinical practices will undergo changes accordingly.

03 Oncology Frontier: The DESTINY-Breast12 study reported some adverse reactions associated with T-DXd, particularly the incidence of interstitial lung disease (ILD)/pneumonitis. Based on your clinical experience, how can we balance its efficacy and safety in treatment?

Dr. Yongmei Yin: T-DXd is one of the most effective anti-HER2 ADC drugs for treating HER2-positive brain metastasis patients. In the DB-01, DB-02, and DB-03 studies, we observed cases of interstitial pneumonia occurring during treatment with T-DXd. However, in general, the incidence of interstitial pneumonia among patients treated with T-DXd in China over the past two years appears to be lower than the rates reported in the DB-01, DB-02, and DB-03 studies.

As the Leading PI, I am also leading a nationwide, multicenter real-world study on T-DXd in treating HER2-positive brain metastasis patients. This study will objectively assess the incidence of interstitial pneumonia in Chinese patients and the severity of these cases. From our current clinical practice data, the overall incidence of interstitial pneumonia in patients treated with T-DXd is relatively low, and the symptoms are generally mild. Real-world data will provide us with more objective insights into the incidence and management of interstitial pneumonia, helping improve patient outcomes.

Dr. Yongmei Yin

• Vice President, Jiangsu Provincial Hospital
• Professor, Chief Physician, PhD Supervisor
• Vice President of the Chinese Society of Clinical Oncology (CSCO)
• Secretary General of the CSCO Breast Cancer Expert Committee
• Chair of the CSCO Patient Education Expert Committee
• Deputy Chair of the CSCO Smart Healthcare Expert Committee
• Executive Member of the Chinese Anti-Cancer Association (CACA) Breast Cancer Professional Committee (CBCS)
• Deputy Chair of the Precision Medicine Breast Cancer Professional Committee of the Chinese Medical Doctor Association