*For medical professionals only for reference
Famous experts in Shanghai gathered together, colliding with sparks of wisdom, and playing the academic strong voice of the Four Seas Association.
The sea embraces all rivers and looks at the world; all the wise men arrive, and the seat is full of prosperity. In order to build a platform for interactive communication among young and middle-aged scholars and promote the development and progress of the field of diagnosis and treatment of breast cancer , the Sihai Conference, sponsored by the Breast Cancer Professional Youth Committee of the Shanghai Anti-Cancer Association, was grandly held in Shanghai on October 30, 2022. This conference specially invited Professor Liu Guangyu from the Cancer Hospital of Fudan University as the honorary chairman, Professor Yu Keda from the Cancer Hospital of Fudan University and Professor Jin Yiting from the Huashan Hospital of Fudan University as the chairman, and gathered young experts and scholars in the field of breast cancer to discuss the progress of cutting-edge diagnosis and treatment, inspire clinical diagnosis and treatment thinking, and show academic style.
Figure 1. Participants took photos
to keep their love, and went to the mountains and seas
at the beginning of the meeting, Professor Jin Yiting introduced that in recent years, the development of ADC drugs has been shining. Today's special topics focus more on the progress and controversy of ADC drugs. At the same time, there are also links such as breast cancer laparoscopic surgery, in-depth interpretation of major research, and enthusiastic debate competitions from the perspective of young doctors. I hope that everyone can actively show themselves on today's stage. Professor Liu Guangyu, Honorary Chairman of
, mentioned that the Four Seas Society literally has the meaning of exploring the four seasons, and is full of the profoundness of embracing all rivers and looking at the world. I hope that under the leadership of Professor Yu Keda, everyone will know all the people from all over the world and continue to learn from medical skills and make progress together. At the same time, he pointed out that the development of young doctors should be tolerant, critical and concise, and hopes to encourage everyone. In his speech, Professor Keda expressed his expectations that under the shadow of the epidemic, even if the weather changes, everyone will still go to the mountains and seas together, constantly forging ahead on the academic road and improving themselves. And I sincerely hope that Sihai will not only be held in Shanghai, but will develop into different cities across the country so that all the peers can participate.
Figure 2. Professor Liu Guangyu's opening speech
Figure 3. Professor Yu Keda's opening speech
Figure 4. Professor Jin Yiting's opening speech
Knowledge iteration, creating the future
ADC leads breast cancer anti-HER2 diagnosis and treatment future
ADC leads breast cancer anti-HER2 diagnosis and treatment future
Chapter 1 Under the co-chair of Professor Yu Keda and Professor Jiang Yizhou, Professor Fan Lei of Fudan University Affiliated Cancer Hospital first shared the wonderful topic of "ADC leads the future of breast cancer anti-HER2 diagnosis and treatment future". Professor Fan Lei systematically explained the research and development background and design concept of ADC drugs. Among them, the new ADC drug DS-8201 uses a cleavable linker based on tetrapeptides and a highly active topoisomerase I inhibitor as a drug-loaded drug, and the drug antibody ratio (DAR) reaches 8, and has a strong bystander effect. Its unique structural and mechanism attributes have great advantages over the current series of anti-HER2 ADCs.
When talking about the clinical value of the new ADC drug to HER2-positive breast cancer, Professor Fan Lei said that the progression-free survival (PFS) of previous first-line treatment for HER2-positive advanced breast cancer was about 20 months, and the second-line treatment was only 6-10 months. However, the amazing performance of DS-8201 in the DESTINY-Breast03 (DB-03) study rewritten this situation. The median PFS evaluated by the investigator was as long as 25.1 months, with a P value as low as 10-22. In all subgroups, DS-8201 showed an absolute PFS (BICR) benefit advantage over T-DM1. The objective response rate (ORR) is as high as 79.7%, and the tumor shrinkage effect is very significant. Based on this research result, DS-8201 has successively obtained second-line treatment recommendations from authoritative domestic and foreign guidelines, and has also used it as a second-line "optional" recommendation in the 2022 CBCS Essential Edition Guide (Xiaohongshu). Although there is no head-to-head study comparison, DS-8201 shows its efficacy advantages over other HER2-targeted ADC drugs, and its overall safety is good, and the actual incidence of intermediate pneumonia (ILD) is relatively low. Not only that, DS-8201 is also actively deploying early (new) assisted and advanced first-line treatment, covering the future of HER2-positive breast cancer with full coverage.
For HER2 low-expression breast cancer, Professor Fan Lei emphasized that low HER2 expression accounts for about 50% of the total breast cancer. At present, there is still controversy over whether low HER2 expression can become a unique breast cancer subgroup, but most studies believe that it has a large correlation with HR status, and overall low HER2 expression does not indicate a worse prognostic outcome. Based on the breakthrough results of DESTINY-Breast04 (DB-04) research, DS-8201 has been recommended as a class of evidence for HER2-low expression of breast cancer (regardless of HR status) by the NCCN guidelines. In 2022, Xiaohongshu also regards it as an "optional" post-line treatment recommendation for HR-positive patients.
Finally, Professor Fan Lei systematically sorted out the R&D trends and future prospects of ADC drugs. The focus of future R&D of ADC drugs is mainly to overcome drug resistance and reduce toxicity. In the future, bispecific antibody , immunostimulated drug-loaded ADC, dual drug-loaded ADC, radionuclide ADC, etc. will all become the exploration directions for the precise upgrade of ADC drugs. In the future, more drug development may be carried out for biomarker , especially gene mutations and protein-specific expression.
Figure 5. Professor Fan Lei
How to view the development and status of laparoscopic surgery for breast cancer
Oncology Hospital Affiliated to Fudan University Professor Martin gave a wonderful explanation of the current status and future development of laparoscopic surgery in breast cancer from the two aspects of breast conservation surgery and total mammary incision and reconstruction surgery, and took on oncological safety and patient satisfaction (cosmetic effect) as the main considerations, and gave a wonderful explanation of the current status and future development of laparoscopic surgery in breast cancer. The cosmetic effect of laparoscopic breast-conserving surgery for breast cancer is limited and there are few suitable patients; and in terms of safety, there is a lack of high-quality long-term follow-up data support, and the incision is a key limiting factor. Laparoscopic mastectomy and reconstructive surgery are suitable for patients with high cosmetic requirements and appropriate conditions. Although there are relatively more research data compared with breast-conserving surgery and some good retrospective data support its safety, prospective research evidence still requires more detailed clinical guidance.
Professor Martin said that laparoscopic surgery for breast cancer is expected to become a beneficial supplement to the existing surgical system, but the next decade will still be a stage of gradually accumulating data. It is not appropriate to carry out blindly on a large-scale scale at present, and it is more necessary to develop more standardized and orderly. Specifically, it includes the need for better clinical evidence, standardized operational training, scientific case selection, and strict qualification certification.
Figure 6. Professor Martin
Foresee the future
Then, under the leadership of Professor Jiang Yizhou, Professor Xiao Qin, Professor Zhang Yingying, and Professor Zhao Junyong, Shanghai Tenth People's Hospital Affiliated to Tongji University, expressed their views on the above topic: the excellent efficacy of DS-8201 is undoubtedly, and the overall safety is good, and its future application prospects are also desirable. Laparoscopic surgery for breast cancer can be used as a supplement to mainstream technology, but it is currently generally conservative about its clinical application.
Mountains are high and the moon is wide, bravely climbing the peak
New progress in targeted treatment of early breast cancer
Chapter 2 Under the auspicious leadership of Professor Jin Yiting and Professor Huang Liang, the academic link was first explained by Professor Qin Wenxing, Affiliated to the four early breast cancer targeted treatments, namely I-SPY2, PREDIX HER2, TRAIN-2, and Per ELISA, and explained how to evaluate the efficacy of early breast cancer targeted treatments, and discussed related topics about whether existing immunohistochemical molecular typing can truly predict clinical efficacy. Among them, the TRAIN-2 study subgroup analysis showed that the TIL score was not significantly correlated with the prognosis of HER2-positive breast cancer patients receiving chemotherapy + anti-HER2 dual-target neoadjuvant therapy. However, this study shows that gene detection has a good suggestive effect on patients' prognosis. Per ELISA study showed that the HER2DX pCR score and HER2DX ERBB2 score were positively correlated with the pCR rate obtained by neoadjuvant trapa dual-target + letrozole (dechemotherapy) regimen selected according to the Ki67 baseline response after two weeks of letrozole treatment. The study results suggest possible predictors and are of great significance for screening out HR+/HER2+ populations that can be exempted from chemotherapy.
Finally, Professor Qin Wenxing said that overall, the relevant research on efficacy predictors is very popular at present, and there are also many progress in the field of targeted treatment of early breast cancer. For example, the DESTINY-Breast11 (DB-11) study of the new ADC drug DS-8201 neoadjuvant treatment, and the DESTINY-Breast05 (DB-05) study of neoadjuvant residual lesions are all in full swing. I believe that the release of future research results will further improve patient survival and change the targeted treatment pattern of early breast cancer.
Figure 7. Professor Qin Wenxing
is harmless first: cancer risk after breast cancer treatment
000001. Professor Yang Zhaozhi, an Affiliated Cancer Hospital of Fudan University, gave a detailed interpretation of the retrospective cohort study of breast cancer-related soft tissue sarcoma in breast cancer treatment . The data from the Kaiser Permanente (KP) cohort and SEER 13 registered research cohort. The results showed that among the 15,940 eligible female breast cancer patients with evaluable conditions, 19 (0.1%) developed chest soft tissue sarcoma (11 hemangiosarcoma and 8 other subtypes). Most (94.7%; 18/19) chest soft tissue sarcoma occur in female patients receiving radiotherapy; therefore, radiotherapy is associated with a significant increase in the risk of chest soft tissue sarcoma (RR=8.1; p=0.0052), but not with prescription dose, segmentation, or push. In the SEER cohort, 430 (0.1%) of 457,300 patients (0.1%) were secondary to chest soft tissue sarcoma (268 hemangiosarcoma and 162 other subtypes) after median follow-up of 8.3 years (IQR 4.3-13.9). The majority (77.9%; 335/430) cases occurred after radiotherapy; it also suggested that radiotherapy was associated with a significant increase in the risk of chest soft tissue sarcoma (RR=3.0; p0.0001). Based on the results of this research, Professor Yang Zhaozhi said that radiotherapy for breast cancer is a double-edged sword. When treating, you need to weigh the pros and cons and try to make all treatment decisions without harming the patients, in order to maximize the benefits of treatment.
Figure 8. Professor Yang Zhaozhi
Pulse
Next, under the leadership of Professor Huang Liang, Professor Chen Jiajian of the Cancer Hospital of Fudan University, Professor Chu Chengyu of Huashan Hospital of Fudan University, and Professor Wang Zhengyuan of Shanghai Jiahui International Hospital respectively expressed profound insights on the relevant content of the above topics. The main views include: ADC drugs are an important exploration direction for targeted treatment of early breast cancer in the future. Overall The trend is to screen out key targets, combine with the constantly updated and iterative technologies to develop a broader ADC drug; with the disclosure of research data on DB-11 and DB-05 in the later stage, DS-8201 will undoubtedly bring a new round of treatment changes to HER2-positive early breast cancer; it is very important to fully communicate with patients before breast conservation surgery, and it is necessary to objectively inform the risk of the second primary tumor after radiotherapy, and fully analyze the benefit risk ratio to better make clinical decisions.
is in his prime, and he lives up to his youth and is surprised by the people. Under the leadership of Professor Zhang Jian , the Affiliated Cancer Hospital of Fudan University, the meeting was held in a passionate debate session. The experts at the meeting discussed "Advanced Second-line ADC (DS-8201) or TKI (pyrrolitinib) after the first-line treatment of HER2 positive advanced breast cancer." Yueyang Integrated Traditional Chinese and Western Medicine Hospital affiliated to Shanghai University of Traditional Chinese Medicine Professor Ji Yajie, Professor Ye Xin, International Peace Maternal and Child Health Hospital affiliated to Shanghai Jiaotong University School of Medicine, and Professor Zhuang Ming, Professor DS-8201 as a positive debater. Yangpu Hospital Affiliated to Tongji University Professor Cai Fengfeng, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine Professor Cao Lu, and Professor Wang Min of the First People's Hospital Affiliated to Shanghai Jiaotong University as opposing debaters support pyrrotinib. Defenders from both sides made fierce debates around the following topics, pushing the entire meeting to a climax of the atmosphere.
Figure 9. The guest of the debate competition
has the exact efficacy, and the guide escort
The positive view:
Thanks to its unique structure and mechanism attributes, DS-8201 can be called "excellent talent, cheating at the beginning, fighting alone, killing all the way." Single-agent second-line treatment has brought unprecedented PFS benefits to patients with HER2-positive metastatic breast cancer (25.1 months), and the ORR is as high as 79.7%.It is worth mentioning that the DB-03 study not only included patients who have received trastuzumab and TKI treatment, but also included about 60% of trapa dual-target patients, which is more in line with China's current clinical practice. In addition, a considerable proportion of Asian patients were enrolled in the DB-03 study, of which 57.1% were Asian people in the DS-8201 group, and 23.5% were Chinese patients, and the treatment benefits of Asian subgroup patients were consistent with the overall population. Therefore, DS-8201 is well deserved as the "strongest warrior" of a single drug. Based on the outstanding achievements of DB-03 research, DS-8201 has been recommended by domestic and foreign guidelines as a new second-line treatment standard for HER2-positive advanced breast cancer.
Opposite view:
PHENIX and PHOEBE two phase 5III clinical studies jointly confirmed the excellent efficacy of pyrrolitinib in Chinese patients, and ORR (PHENIX: 68.6%; PHOEBE: 67.2%) and PFS (PHENIX: 11.1 months; PHOEBE: 12.5 months) both improved significantly. At present, pyrrolitinib is the second-line preferred solution recommended by many domestic guidelines. And since its approval for marketing, its efficacy has been verified by a number of real-world research data.
Stability and active brain metastasis are effective
positive view:
DB-03 study included 23.8% of patients with stable brain metastasis, the median PFS of the subgroup reached 15 months, and the intracranial ORR was as high as 64%, among which CR patients also accounted for 27.8%, surpassing the benefit data of patients with stable brain metastasis in previous DB-01 studies. Not only that, DS-8201's performance in active brain metastasis is also remarkable. TUXEDO-1 study shows that DS-8201 has an intracranial ORR of 73.3% for treating active brain metastasis and PFS lasts for 14 months. Whether it is stable brain metastasis or active brain metastasis, DS-8201 performed well.
Opposite view:
pyrrolitinib, as a small molecule TKI, is easy to penetrate the blood-brain barrier. PHENIX study showed that pyrrolitinib was also effective in patients with stable brain metastasis at baseline (PFS was 6.9 months). The PERMEATE study showed that patients with active brain metastasis who had not received radiotherapy had PFS of 11.3 months and the intracranial ORR reached 74.6%.
side reaction is small, safe and reliable
positive view: In the study of
DB-03, the incidence of grade ≥3 diarrhea was lower (0.4%). The incidence of ILD at any level is 10.9%, and most are grades 1 and 2, and the incidence of 3 is 0.8%, and there is no grades 4 and 5. Most ILD events were recovered during continuous follow-up and no fatal pneumonia occurred. In addition, the incidence of early-line ILD is lower, which is different from the perception of clinical experts. In addition, the continuous treatment time of DS-8201 can reach 14.3 months, with a treatment interruption rate of 35.4% and a dose adjustment rate of 21.4%; while the incidence of grade ≥3 diarrhea in the Phase III clinical trial of pyrrolitinib was 31%-46.5%, with a treatment interruption rate of 54.2%-61.9%, and a dose adjustment rate of 25.9%-47%. Overall, DS-8201 is safe and can be tolerated by patients ongoing use.
Opposite view:
pyrrolitinib second-line treatment is safe and does not cause ILD. In the PHOEBE study, the adverse events of ≥3 in pyrrolitinib group, only diarrhea (30.6%) was common. As the treatment progressed, the incidence of diarrhea gradually decreased, and the accumulation of grade 3 diarrhea lasted for only about 1 week, which was easy to manage clinically.
assist moment, wonderful continued
After the debate between the two sides, the wonderful "assisted moment" was immediately ushered in. Under the auspices of Professor Ge Rui from East China Hospital Affiliated to Fudan University, Professor Cao Jun and Professor Tao Zhonghua from Fudan University Affiliated to Fudan University respectively explained their views on "assistance". Both professors highly affirmed the excellent efficacy of DS-8201 and mentioned that any treatment needs a comprehensive layout to give full play to the efficacy value of the drug. We look forward to the exploration of more joint solutions for DS-8201.
quotes classics and talks freely about
The final part of the meeting was hosted by Professor Qu Qing, Professor Shanghai Changhai Hospital , Professor Yu Yue shared the wonderful topic of "The Integration of Knowledge and Action of Breast Surgeons".Professor Yu Yue ingeniously explained the process of establishing the philosophical system of the historical saint Wang Yangming, and explained in a simple and easy-to-understand way, as a breast surgeon, how to continuously accumulate theoretical knowledge while putting it into clinical practice while adhering to the original intention, truly achieve "integration of knowledge and action" in order to benefit the vast number of patients. Finally, Professor Yu Yue summarized this report with a poem by Wang Yangming, "I have a Zhongni in my heart, and I will be confused by hearing and seeing hardships, but now I refer to the true head and face, but I have no doubts about my conscience." He also called on fellow doctors to carry forward the conscience in my heart and make more contributions to others and society.
Figure 10. Professor Yu Yue
ended. Professor Yu Keda gave a deep insight on the above debate session, "From the current form, there is actually a time difference in our debate topic today, because the life cycle of each drug is not consistent with the development. The second-line treatment status of DS-8201 has gradually been consolidated and become more solid, and with the new evidence-based results, it will move to the front line. Here, I also wish that every drug can obtain a good therapeutic status and application prospect, and ultimately benefit patients." Professor Jin Yiting concluded that this conference not only included the latest field research progress, but also brought together the profound insights and thoughts of multidisciplinary doctors on breast cancer diagnosis and treatment. Not only did it set up a tense and exciting debate competition, but it also carefully arranged a reflection of humanistic knowledge sharing. All the scholars attending the meeting were passionate and talented, presenting a commendable academic feast. I hope that through this knowledgeable and eloquent exchange conference, everyone can think and gain something, and strive to contribute to the diagnosis and treatment development in the field of breast cancer. Finally, I also hope that when the next game of the Four Seas will come, all the young talents present can continue to make rapid progress and create new glory.
*This article is only used to provide scientific information to medical personnel and does not represent the views of this platform
