Editor’s note : As time passes and seasons flow, we always embark on new journeys and endeavors through repeated reviews and outlooks. The annual review of the Northern Breast Cancer Salon and the discussion on the 2024 CSCO BC Guidelines update were held from January 5-6, 2024, in Beijing. “Oncology Frontier” specially interviewed Professor Rui Ge from East Hospital affiliated with Fudan University to reflect on the progress in breast cancer treatment in 2023 and share his insights on the content of interest in the 2024 CSCO BC Guidelines update.

Oncology Frontier : Currently, immunotherapy has shown some benefits in the treatment of HR+/HER2- breast cancer patients. Do you see a promising future for the application of immunotherapy in this field, and could you comment on relevant studies?

Professor Rui Ge : Immunotherapy was first applied in triple-negative breast cancer patients, and we have seen varying results from different studies in this area. For HR+/HER2- breast cancer patients, more patients opt for neoadjuvant chemotherapy, and some choose neoadjuvant endocrine therapy, but the pCR rates are not very high, so there is an urgent need for better treatment strategies to improve pCR rates for these patients. Moreover, if the pCR rate for HR+/HER2- breast cancer patients could be improved, it could also lead to better prognoses. Therefore, we need to try combining other treatment plans.

At the 2023 ESMO conference, the results of the KEYNOTE-756 and CheckMate 7FL studies were announced, demonstrating the feasibility of using immunotherapy in HR+/HER2- breast cancer patients, with the data also presented at the 2023 SABCS conference. Both studies were similar in design, combining chemotherapy with immunotherapy to see if it could further enhance treatment efficacy. In these studies, we saw an increase in pCR rates in the ITT population, especially among patients with higher immune expression, and we look forward to more effective data from these studies in the future.

It is worth noting that after the neoadjuvant phase of the CheckMate 7FL study, evidence for intensified adjuvant treatment with CDK4/6 inhibitors was already established, so immunotherapy was not continued in the adjuvant phase of the CheckMate 7FL study. Thus, we look forward to the results of the KEYNOTE-756 study, which applied immunotherapy throughout the neoadjuvant and adjuvant phases, hoping to achieve better clinical treatment effects.

Personally, I believe that immunotherapy offers more hope for treatment in HR+/HER2- breast cancer patients. We hope that the addition of immunotherapy not only brings higher pCR rates to patients but also better long-term treatment effects. At the same time, we are also looking to identify the populations that can benefit from immunotherapy and find biomarkers that can guide us in optimizing clinical strategies.

Oncology Frontier : Looking back on 2023, which studies in the field of breast cancer treatment impressed you the most? Please share.

Professor Rui Ge : There were many impressive studies in 2023, and I will introduce them separately. First, the progress of CDK4/6 inhibitors in the area of adjuvant intensification therapy. Based on updated follow-up results from the monarch E study, its therapeutic advantage continues to expand. After two years of intensified therapy with abemaciclib, the risk of disease recurrence in patients was reduced. At this year’s ASCO meeting, the results of the NATELEE study added evidence-based medical evidence for the application of CDK4/6 inhibitors in the field of adjuvant intensification therapy. The NATELEE study also included some lymph node-negative patients, thus broadening the scope of adjuvant intensification therapy. Additionally, in the NATELEE study, the dose of ribociclib was adjusted to 400mg, further reducing adverse reactions during treatment and improving patient compliance. Therefore, I believe that these two study results can to some extent promote the application of CDK4/6 inhibitors in the neoadjuvant treatment field.

Second, the clinical application of ADC drugs. Currently, HER2 expression status can be divided into three categories: HER2 overexpression, HER2 low expression, and HER2 zero expression. In patients with HER2 overexpression, the ADC drug T-DM1 has already been included in medical insurance, and the accessibility of T-DXd has greatly increased. Studies on T-DXd treatment for brain metastases are also continuously being updated. Additionally, DESTINY-Breast04 is the first phase III study to achieve positive results in the treatment field of HER2 low-expressed breast cancer. The publication of this study’s results not only showed the benefits of T-DXd in these patients (the latest data published at the

2023 ESMO conference showed that in HR+ patients, the median OS for the T-DXd group reached 23.9 months compared to 17.6 months for the TPC group, HR=0.69), but also led to more studies focusing on the HER2 low expression population and established HER2 low expression as a treatment category for breast cancer, changing the treatment landscape. Also, the appearance of HER2 low expression breast cancer patients as an independent treatment subtype has raised higher demands for HER2 testing samples, testing processes, testing methods, and cut-off values.

In 2023, the data for the anti-Trop-2 ADC drug, sacituzumab govitecan (SG), also continued to be enriched. The results of the EVER-132-001 study showed that previously treated mTNBC patients in China receiving SG treatment had prolonged median OS. For HR+/HER2- breast cancer patients who failed CDK4/6 inhibitor treatment, SG also showed good therapeutic effects. The publication of research data for the domestically produced anti-Trop-2 ADC drug SKB264 also gave us more confidence in treatment. In addition, studies combining ADC drugs with immunotherapy are also being explored. I believe the conduct of ADC drug-related studies can further promote their clinical application.

Oncology Frontier : In the discussion on the 2024 CSCO BC Guidelines update, which subtype of breast cancer guideline updates are you most interested in? Please introduce the relevant content.

Professor Rui Ge : I am particularly concerned with the treatment of HR+/HER2- advanced breast cancer patients. In this treatment area, we will stratify based on patients’ previous drug treatment choices, but there is still much to look forward to and explore in the post-CDK4/6 inhibitor treatment era. Thus, I am hopeful that with this year’s adjustments in medical insurance policies and the increased accessibility of certain treatment drugs, the treatment strategies for patients who have previously used CDK4/6 inhibitors can be optimized. I hope that through expert discussions at this conference, we can better guide clinicians in making treatment decisions. I believe that as more research data are published, the updates to the related guidelines for the treatment field of HR+/HER2- early breast cancer patients will also become clearer.

Additionally, as drug accessibility changes, new evidence has emerged for both first-line and second-line treatment in patients with HER2 overexpression. I believe that with the enhancement of drug accessibility and the implementation of medical insurance policies, the new guidelines will also undergo corresponding changes and adjustments, and we are looking forward to the publication of the expert group’s discussion results.

Professor Rui Ge

Vice Director of Breast and Thyroid Surgery, East Hospital affiliated with Fudan University

Vice Chairman of the CSCO Young Experts Committee

Vice Chairman of the Breast Cancer Committee of the Shanghai Anti-Cancer Association

Member of the Cancer Education Committee of the National Health Commission Capacity Building and Continuing Education Center

Member of the CSCO Breast Cancer Committee

Member of the CBCS of the Chinese Anti-Cancer Association

Standing Committee Member of the Breast Disease Branch of the China International Exchange and Promotive Association for Medical and Health Care

Member of the CSCO Patient Education Committee

Member of the Breast Professional Committee of the Chinese Research Hospital Association

Vice Chairman of the Breast Health Science Committee of the Shanghai Science Popularization Volunteer Association

Standing Committee Member of the Cancer Rehabilitation and Palliative Care Committee of the Shanghai Anti-Cancer Association

Member of the Breast Cancer Committee of the Shanghai Anti-Cancer Association

Class leader of the First Medical New Stars Plan Professional Class of the Shanghai Health Development Foundation

Editorial board member of CA Chinese Edition, peer reviewer for Frontiers in Oncology and JNCC, junior editor for the Chinese Journal of Oncology