With the continuous progress in the field of breast cancer treatment, precision medicine is gradually becoming the key to improving treatment outcomes. At the 2024 ESMO ASIA Annual Meeting, Prof. Biyun Wang from Fudan University Shanghai Cancer Center delivered a proffered oral presentation in the "Proffered Paper session: Breast cancer" session, introducing to colleagues around the world the latest research findings of her team in screening and guiding first-line treatment of HR+/HER2- metastatic breast cancer with 18F-FES PET/CT. After the presentation, Oncology Frontier specially invited Professor Wang Biyun for an interview. She provided us with a detailed interpretation of the background, significance, challenges, and innovation points of this study, and also looked forward to the research directions in the field of HR+/HER2- breast cancer treatment in the future, hoping to provide valuable references and inspiration for the majority of clinicians and researchers.

Oncology Frontier: Could you share the background of your real-world study on 18F-FES PET/CT to guide first-line treatment for HR+/HER2- metastatic breast cancer (MBC)?

Prof. Biyun Wang: Our study aimed to explore the use of 18F-FES PET/CT in guiding first-line treatment for HR+/HER2- metastatic breast cancer patients in real-world settings. This investigation was driven by the following reasons:

Although CDK4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) are the standard first-line treatment for HR+/HER2- advanced breast cancer, a subset of patients does not achieve survival benefits with this approach. Retrospective studies had previously suggested that 18F-FES PET/CT holds significant value in guiding endocrine or chemotherapy decisions for HR+/HER2- advanced breast cancer patients.

To validate this further, we conducted a real-world study with a cohort of 432 patients, comparing those who underwent initial treatment guided by 18F-FES PET/CT screening to those who did not. The findings underscore the critical role of 18F-FES PET/CT in guiding treatment decisions in real-world clinical practice.

Oncology Frontier: Your study showed that patients screened with 18F-FES PET/CT had better outcomes than those who did not undergo screening. What is the clinical significance of this finding for HR+/HER2- breast cancer treatment?

Prof. Biyun Wang: In our study, we retrospectively analyzed the medical records of HR+/HER2- MBC patients diagnosed at Fudan University Shanghai Cancer Center between 2020 and 2023. A total of 432 patients receiving either CDK4/6i combined with ET or chemotherapy (CT) as first-line treatment were included, with or without 18F-FES PET/CT screening before treatment.

• Screened Group: 155 patients (35.9%) underwent FES-PET/CT screening before first-line treatment. Among them, 111 patients with ER-positive metastatic lesions and 17 with ER-heterogeneous lesions received CDK4/6i + ET, while 21 with ER-negative lesions and 6 with ER-heterogeneous lesions received CT.
• Non-Screened Group: 277 patients (64.1%) did not undergo FES-PET/CT screening. Of these, 202 received CDK4/6i + ET, and 75 received CT.

The results revealed significant differences in progression-free survival (PFS):

• In the CDK4/6i + ET cohort, the median PFS (mPFS) was significantly longer for the screened group (32.4 months) compared to the non-screened group (18.0 months) (HR = 0.48; 95% CI: 0.34–0.69; P < 0.0001).
• In the CT cohort, the screened group also had a better mPFS (11.35 months) compared to the non-screened group (8.91 months) (HR = 0.56; 95% CI: 0.33–0.97; P = 0.035).

This finding has substantial clinical implications for treating HR+/HER2- breast cancer. Previously, treatment decisions for HR+/HER2- advanced breast cancer were based on ER immunohistochemistry results from metastatic lesions. However, in clinical practice, some patients cannot undergo testing post-metastasis, and tumor heterogeneity often complicates treatment choices. The use of 18F-FES PET/CT allows clinicians to make more precise treatment decisions tailored to individual patients.

Our findings indicate that FES-ER-positive patients benefit significantly from CDK4/6i + ET, while FES-ER-negative patients are better suited for chemotherapy. This evidence highlights the value of 18F-FES PET/CT as a critical tool in guiding therapy selection.

Additionally, subgroup analysis for endocrine-resistant patients revealed that those in the screened group treated with ET had a significantly longer mPFS (28.3 months) than those in the non-screened group (16.0 months) (HR = 0.59; 95% CI: 0.39–0.88; P = 0.0097). Notably, this difference was not observed in the CT cohort. These findings demonstrate that 18F-FES PET/CT screening effectively identifies endocrine-resistant patients who would benefit from CDK4/6i + ET, offering a promising approach to improve outcomes for this population.

Thus, 18F-FES PET/CT screening has the potential to become an essential reference for treatment decisions in HR+/HER2- breast cancer patients.

Oncology Frontier: During the initiation of this study, what were the main challenges you and your team faced, and how did you overcome them? Additionally, what were the key innovations of this research?

Prof. Biyun Wang: The main challenges during the study included efficiently integrating information from various sources, as this was a collaborative effort with the nuclear medicine department, and managing a relatively large patient cohort. To overcome these challenges, our team engaged in close collaboration, leveraging each member’s expertise to address specific aspects of the study. Ultimately, through the collective effort and cooperation of all team members, we successfully completed this research.

The innovations of this study are reflected in two main aspects:

1. Real-world validation with a large cohort: For the first time in a real-world setting, we demonstrated the role of 18F-FES PET/CT screening in guiding first-line treatment for HR+/HER2- advanced breast cancer patients using a relatively large sample size (432 patients).
2. New applications in precision treatment: Beyond confirming the value of 18F-FES PET/CT in assessing ER status, our study explored its potential to guide treatment decisions, offering new strategies and methods for precision therapy in HR+/HER2- breast cancer.

Oncology Frontier: Based on the current findings, what are your future research plans for the treatment of HR+/HER2- metastatic breast cancer? Specifically, how can 18F-FES PET/CT be better promoted and utilized?

Prof. Biyun Wang: Building on our current findings, we have the following plans and outlooks for future research in HR+/HER2- metastatic breast cancer:

1. Promoting and expanding 18F-FES PET/CT: The current availability of 18F-FES PET/CT in domestic medical centers is limited, restricting its broader application. We hope that the results of our study will encourage more medical institutions to adopt and master this technology, ultimately benefiting more HR+/HER2- metastatic breast cancer patients.
2. Conducting prospective studies: We plan to undertake prospective studies to investigate treatment differences in heterogeneous breast cancer patients receiving chemotherapy or endocrine therapy. This will enable us to better guide treatment decisions tailored to individual patient profiles.
3. Exploring the correlation between FES expression and prognosis: After my presentation, a colleague raised a question about whether the degree of FES expression correlates with patient prognosis. This is an important area that we plan to focus on in future research.

Through these efforts, we aim to deepen the understanding and application of 18F-FES PET/CT while continuing to advance precision therapy for HR+/HER2- breast cancer.

Prof. Biyun Wang

• Department of Oncology, Fudan University Shanghai Cancer Center
• Director of Breast and Uro-Oncology Division
• Chief Physician and Master’s Supervisor
• Executive Member, Chinese Society of Clinical Oncology (CSCO)
• Chair, Youth Committee, CSCO
• Secretary-General and Standing Member, CSCO Patient Education Expert Committee
• Member, CSCO Breast Cancer Expert Committee
• Chair, CRPC Committee, Shanghai Anti-Cancer Association
• Standing Member, Breast Cancer Committee, Shanghai Anti-Cancer Association