Editor's Note: On July 27-28, 2024, the "2024 Breast Cancer Summer Forum·Northern Salon" was grandly held at the Shougang Park in Beijing. The conference adhered to the concept of "learning, absorbing, innovating, and improving" and embraced the tradition of "All directions, Throughout time and across the world, Across all seasons, People of all ages and genders" offering an academic feast in the midsummer. In the era of immunotherapy, triple-negative breast cancer (TNBC) has broken through bottlenecks, achieving survival benefits in both short-term and long-term efficacy. After the TNBC session, Dr. Cuizhi Geng from The Fourth Hospital of Hebei Medical University, Dr. Haibo Wang from The First Clinical Medical College of Qingdao University, Dr. Tao Wang from the Chinese PLA General Hospital, and Dr. Kun Wang from the Guangdong Provincial People's Hospital discussed the present and future of TNBC immunotherapy, guiding the development of precision and individualized immunotherapy. Dr. Cuizhi Geng: What are the significant advancements in immunotherapy for early-stage triple-negative breast cancer (TNBC)?
Dr. Haibo Wang: For early-stage TNBC, chemotherapy was the primary treatment, but it was relatively limited. The advent of immunotherapy has brought new hope. The KEYNOTE-522 study and the IMpassion 030 study explored neoadjuvant therapy. Results published in 2023 from the KEYNOTE-522 study showed that combining chemotherapy with neoadjuvant immunotherapy increased the pathological complete response (pCR) rate by 13.6% and the 5-year event-free survival (EFS) rate by 9% compared to chemotherapy alone. Different PD-L1 CPS subgroups and various disease stages all benefited. In the adjuvant treatment stage, continuing with 9 cycles of immune-enhancing adjuvant therapy for both pCR and non-pCR patients resulted in higher EFS benefits compared to the placebo group. This study brought promising data for early-stage TNBC immunotherapy. However, the IMpassion 030 study did not show an invasive disease-free survival (iDFS) benefit with immune adjuvant therapy compared to chemotherapy, indicating that further exploration is needed for early-stage TNBC immune adjuvant therapy. Breast cancer is generally a low immunogenic tumor. Apart from TNBC, other subtypes have also explored immunotherapy options. In HER2-positive breast cancer, there is hope, but clinical application is not yet realized; for hormone receptor (HR)-positive breast cancer, the CheckMate 7FL and KEYNOTE-756 studies have shown initial efficacy of early application of immune combination therapy, with long-term follow-up data hoped to guide clinical application in the future. Therefore, for early-stage breast cancer immunotherapy, further exploration is necessary, including different breast cancer subtypes, various immune checkpoint inhibitors, and different combination therapy regimens, which may all be future directions of focus.
Dr. Cuizhi Geng: The KEYNOTE-522 study has achieved great results with immunotherapy in the neoadjuvant and adjuvant treatment stages for TNBC. Historically, pCR with neoadjuvant chemotherapy alone for TNBC did not exceed 40%, but the addition of immunotherapy significantly increased the pCR rate to over 60%. The KEYNOTE-522 study also confirmed the good effect of immune adjuvant therapy on EFS, effectively improving patient survival.
Dr. Cuizhi Geng: How does immunotherapy revolutionize first-line traditional treatment for advanced TNBC?
Dr. Tao Wang: Immunotherapy has rapidly developed in other cancers and has gradually progressed from advanced to early adjuvant and neoadjuvant treatment in breast cancer. For advanced TNBC, traditional chemotherapy’s overall survival (OS) is less than a year, and its efficacy has reached a bottleneck. Immunotherapy provides a significant opportunity to break through this bottleneck. Among the various subtypes of breast cancer, TNBC has a higher tumor mutation burden (TMB), higher PD-L1 expression, and richer TIL cell infiltration, indicating potential benefits from immunotherapy. Clinical studies have confirmed this. The KEYNOTE-355 study was one of the first clinical studies to achieve positive results in TNBC immunotherapy, showing that combining PD-1 inhibitor pembrolizumab with chemotherapy benefited both PFS and OS in the PD-L1 CPS≥10 population, with an OS reaching 23.0 months. Thus, pembrolizumab has been approved abroad for first-line treatment of advanced TNBC, although it has not been approved for this indication in China. Fortunately, China’s TORCHLIGHT study showed positive results using the PD-1 inhibitor toripalimab combined with nab-paclitaxel for first-line treatment of advanced TNBC. The study showed that in the PD-L1 CPS≥1 population, the toripalimab group achieved an mPFS of 8.4 months and an OS of 32.8 months, significantly improving compared to the control group. This study was published in “Nature Medicine” (IF: 82.9) and led to the approval of toripalimab for first-line treatment of advanced TNBC by China’s National Medical Products Administration (NMPA), making it the only immunotherapy drug approved for advanced TNBC in China, bringing hope to patients. In clinical practice, we focus on the efficacy of immunotherapy and the potential immune-related adverse events that can affect various body systems. However, we should not be deterred by these adverse effects; with early diagnosis, early detection, and early treatment, immune-related adverse reactions can be managed to ensure patient benefit.
Dr. Cuizhi Geng
Doctor of Surgery, Chief Physician, Second-level Professor, Doctoral Supervisor Vice-Chairman of the Breast Cancer Professional Committee of the Chinese Society of Clinical Oncology Director of the China Anti-Cancer Association Director of the Chinese Society of Clinical Oncology Standing Member of the Breast Cancer Professional Committee of the China Anti-Cancer Association Member of the Breast Cancer Group of the Oncology Branch of the Chinese Medical Association Standing Member of the Breast Disease Expert Training Committee of the Chinese Medical Doctor Association President of the Hebei Cihuai Cancer Prevention Foundation Vice President of the Hebei Women’s Medical Association Vice Chairman of the Hebei Anti-Cancer Association Chairman of the Hebei Breast Cancer Professional Committee
Dr. Haibo Wang
Doctor of Medicine, Chief Physician, Doctoral Supervisor President of the Breast Disease Hospital, The First Clinical Medical College of Qingdao University President of the Clinical and Translational Research Institute of Solid Tumors, Qingdao University Vice Chairman of the Breast Cancer Expert Committee of the Chinese Society of Clinical Oncology Standing Member of the Breast Cancer Professional Committee of the China Anti-Cancer Association Standing Member of the Breast Specialty Training Expert Committee of the Chinese Medical Doctor Association Vice Chairman of the Breast Branch of the Minimally Invasive Committee of the Chinese Medical Doctor Association Standing Member of the Breast Disease Branch of the China Medical Education Association Standing Member of the Breast Reconstruction Branch of the China Medical Promotion Association Chairman of the Breast Disease Branch of the Shandong Rehabilitation Medical Association Chairman-elect of the Breast Branch of the Shandong Clinical Oncology Association Vice Chairman of the Multidisciplinary Collaboration Breast Disease Branch of the Shandong Medical Association
Dr. Tao Wang
Doctor of Medicine, Chief Physician, Professor, Master Supervisor Head of the Fourth Oncology Ward, Oncology Department, Fifth Medical Center of the Chinese PLA General Hospital Vice Chairman of the Neuro-Oncology Professional Committee of the Chinese Society of Clinical Oncology (CSCO) Member of the Breast Disease Expert Committee of CSCO Vice Chairman of the Youth Committee of the Beijing Breast Disease Prevention Society Standing Member of the Breast Disease Professional Committee of the China Anti-Cancer Association
Dr. Kun Wang
Vice President of the Oncology Hospital of Guangdong Provincial People’s Hospital , Doctoral Supervisor Recipient of the 2019 National Famous Doctor Award Recipient of the 2023 People’s Good Doctor – Outstanding Contribution Award in the Field of Breast Cancer Director of the Chinese Society of Clinical Oncology (CSCO) Standing Member of the Breast Cancer Professional Committee of CSCO Standing Member of the Breast Cancer Professional Committee of the China Anti-Cancer Association Vice Chairman of the Breast Disease Branch of the Guangdong Medical Association Chairman of the Youth Committee of the Breast Disease Branch of the Guangdong Medical Association
