Editor’s Note: With the rapid advancement of medical technology, the concept of precision medicine has been widely applied in the diagnosis and treatment of breast cancer. At the 47th San Antonio Breast Cancer Symposium (SABCS) in 2024, Chinese research gained significant attention, showcasing groundbreaking achievements in breast cancer treatment. During the "2024 Straits Breast Forum and the Annual Meeting of the Fujian Medical Association Breast Disease Branch," Oncology Frontier invited Dr. Benlong Yang from Fudan University Shanghai Cancer Center to share insights on the current treatment landscape, recent research progress, and future prospects in the management of hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-positive breast cancer.

Oncology Frontier: The SABCS, a major event in the breast cancer field, recently concluded in San Antonio, USA. Which studies from the conference particularly caught your attention?

Dr. Benlong Yang:This year’s SABCS presented many advancements in precision medicine and de-escalation of local treatments. I was particularly interested in two aspects. First, the breakthrough results from original Chinese drugs. Remarkably, there were three oral presentations on Chinese-developed drugs in the main sessions of SABCS this year, an unprecedented occurrence in the conference’s history.

Academician Binghe Xu from the Cancer Hospital of the Chinese Academy of Medical Sciences presented the final analysis of the PHILA study, focusing on pyrotinib combined with trastuzumab and docetaxel (PyHT regimen) as first-line treatment. The median progression-free survival (PFS) with the PyHT regimen reached 22.1 months, compared to only 10.5 months in the trastuzumab plus docetaxel (HT) group (HR=0.44; one-sided P<0.0001). Moreover, the PyHT regimen showed a trend toward overall survival (OS) benefit, with a hazard ratio (HR) of 0.64 and 3-year OS rates of 80.9% versus 72.4% for the PyHT and HT groups, respectively. This solidifies the role of pyrotinib plus trastuzumab as a first-line therapy for advanced HER2-positive breast cancer.

Professor Junjie Li from Fudan University Shanghai Cancer Center presented results from the FASCINATE-N clinical trial, which investigated the anti-tumor activity and safety of the HER2-targeting antibody-drug conjugate (ADC) SHR-A1811 in neoadjuvant therapy for early-stage HER2-positive breast cancer. SHR-A1811 monotherapy achieved a pathological complete response (pCR) rate of 63.2%, comparable to the 64.4% pCR rate of the standard PCbHP regimen. This “one-versus-four” result highlights the potential of SHR-A1811 as a promising HER2-targeting ADC in both neoadjuvant and adjuvant settings.

Additionally, Professor Zhimin Shao from Fudan University Shanghai Cancer Center reported positive results from a randomized, double-blind, multicenter Phase III trial of neoadjuvant camrelizumab combined with chemotherapy for early or locally advanced triple-negative breast cancer (TNBC). The pCR rate in the camrelizumab group was significantly higher by 12.2% compared to the chemotherapy group (56.8% vs. 44.7%; 95% CI: 3.3–21.2; one-sided P=0.0038). This supports the findings of the KEYNOTE-522 study, demonstrating the superiority of immunotherapy combined with chemotherapy over chemotherapy alone in TNBC neoadjuvant treatment. Notably, the study had unique aspects, such as earlier clinical staging of enrolled patients and a non-significant correlation between pCR results and PD-L1 expression. This research was simultaneously published in JAMA and gained high international recognition.

Besides drug innovations, this year’s SABCS also featured numerous studies on local treatment strategies, particularly focusing on de-escalation. One notable study was the INSEMA trial, which explored the feasibility of omitting sentinel lymph node biopsy (SLNB) in clinically node-negative (cN0) early-stage breast cancer patients undergoing breast-conserving surgery. After a median follow-up of 73.6 months, the study showed non-inferiority in invasive disease-free survival (iDFS) between patients who omitted SLNB and those who received it (HR=0.91; 95% CI: 0.73–1.14). Published in The New England Journal of Medicine, these results provide solid evidence supporting the omission of axillary surgery for select early breast cancer patients.

Oncology Frontier: The emergence of ADCs has significantly transformed clinical practices for HER2-positive breast cancer. At SABCS, many studies explored molecular biomarkers for patient stratification. Could you elaborate on the latest developments in precision treatment for HER2-positive breast cancer?

Dr. Benlong Yang:Treatment options for HER2-positive breast cancer have greatly expanded, especially with the advent of novel ADCs. DS-8201 (trastuzumab deruxtecan, T-DXd) now holds a dominant position in treating HER2-positive breast cancer. The DB03 study compared DS-8201 head-to-head with T-DM1 as second-line therapy for advanced HER2-positive breast cancer. Results confirmed that DS-8201 offers superior efficacy and better safety management, solidifying its role as the second-line standard of care. DS-8201 has also shown promising results in later-line treatments and in patients with low or ultra-low HER2 expression.

However, a critical question remains: do all patients need these new ADCs? For example, studies on the second-generation HER2 ADC T-DM1 in neoadjuvant settings showed that combining it with pertuzumab did not outperform the standard TCBHP regimen. Similarly, the third-generation ADC T-DXd is undergoing neoadjuvant studies (DB-11), but data are yet to be published. This suggests the need for more precise patient selection to avoid overtreatment.

Interestingly, this year’s SABCS featured several attempts at treatment de-escalation, focusing not on anti-HER2 drugs but on the accompanying cytotoxic agents. Adverse events primarily stem from these cytotoxic drugs. Professor Junjie Li’s FASCINATE-N study explored using SHR-A1811 as monotherapy compared to the standard four-drug regimen. If efficacy is comparable, this could lead to regimens using only ADCs or targeted therapies without cytotoxic agents. Additionally, combining CDK4/6 inhibitors with anti-HER2 therapy showed promising results, offering new opportunities for precision treatment in triple-positive breast cancer (HR+, HER2+, TPBC).

Oncology Frontier: De-anthracycline and de-escalation strategies are gaining attention in HER2-positive breast cancer. Based on your clinical experience, how do you view these approaches, and how should efficacy and safety be balanced in practice?

Dr. Benlong Yang:De-escalating chemotherapy in HER2-positive breast cancer is becoming a major trend. The latest “2025 Essential Guidelines for Breast Cancer Diagnosis and Treatment” by the Chinese Anti-Cancer Association and the Chinese Society of Clinical Oncology have listed trastuzumab plus pertuzumab ± endocrine therapy (excluding cytotoxic drugs) as an optional neoadjuvant treatment. This opens the door for early or intermediate-stage HER2-positive breast cancer patients to avoid cytotoxic chemotherapy.

However, the challenge lies in identifying patients suitable for de-escalation. Tools like the HER2DX genomic test, widely used abroad, show promise. It uses 27 gene expressions and clinical features to predict long-term outcomes and pCR potential. I hope similar big-data models will be developed domestically to guide de-escalation strategies effectively. Striking the right balance between efficacy and safety is crucial to ensuring optimal patient outcomes.

About Dr. Benlong Yang:

• Associate Chief Physician, Breast Surgery, Fudan University Shanghai Cancer Center
• PhD in Oncology, mentored by Professor Jiong Wu
• Secretary-General, Integrated Breast Cancer Committee, Chinese Anti-Cancer Association
• Member, Breast Cancer Committee, Chinese Anti-Cancer Association
• Co-Chair, Young Experts Group, Breast Cancer Committee, Chinese Anti-Cancer Association
• Executive Member, Breast Cancer Prevention and Screening Committee, Chinese Anti-Cancer Association
• Expert Member, Breast Surgery Working Group, Chinese Medical Doctor Association
• Founder of the video series “A Bit of Medical Talk with Yang”