Editor’s Note: With the continuous development of medicine and science and technology, the field of breast cancer treatment has seen new breakthroughs. We have witnessed an increasing number of new discoveries and research advancements gradually being applied in clinical practice. These achievements not only enhance the efficiency of breast cancer diagnosis and treatment but also bring more possibilities for breast cancer patients to return to normal life. At the 2024 Southern-Northern Summit, Academician Binghe Xu from the Cancer Hospital of the Chinese Academy of Medical Sciences presented a report on “Progress and Future of Clinical Research in Breast Cancer,” sharing current screening and treatment advancements, and experiences from clinical research at the Cancer Hospital of the Chinese Academy of Medical Sciences. This article reviews his insights.
Global Advances in Breast Cancer Screening and Diagnosis
Screening and Diagnosis Advancements
According to data released by the International Agency for Research on Cancer (IARC) under the World Health Organization in 2020, breast cancer surpassed lung cancer to become the most diagnosed cancer. In China, breast cancer is also the leading malignancy among women, significantly impacting their health.
Development of Diagnostic Technology
Initially, breast cancer diagnosis relied on physical examinations by doctors or other bodily symptoms reported by patients. With the advent of imaging technologies such as X-ray, CT, ultrasound, and MRI, breast cancer mortality rates began to decrease.
The widespread use of imaging technologies in breast cancer screening has increased the screening rates over time. Studies indicate that the detection of small breast tumors (<2 cm or in situ cancers) increased from 36% to 68% after implementing widespread screening, while the detection of large tumors (>2 cm) decreased from 64% to 32%. On May 9, 2023, the U.S. Preventive Services Task Force (USPSTF) recommended starting mammography screening at age 40 instead of 50.
Advances in Surgical Treatment
With the growing emphasis on patient-centered care, breast cancer surgery has evolved from focusing solely on the disease to also considering the patient’s overall well-being. Surgical approaches have progressed from radical mastectomies to modified radical mastectomies, breast-conserving surgeries, and reconstructive surgeries. The scope of surgical removal has decreased, and the rate of postoperative reconstruction has increased. Early-stage breast cancer patients are also experiencing a downward trend in axillary surgery.
Overall, the rate of breast-conserving surgeries has increased, although regional disparities exist, with lower rates in China compared to Western countries.
Advances in Radiation Therapy
Since its clinical introduction, radiation therapy has seen continuous improvements. From standard fractionation, the technology has evolved to include hypofractionation, omission of radiotherapy, partial breast irradiation, intraoperative radiotherapy, and ultrashort fractionation, making breast cancer treatment more precise and convenient. Meta-analyses from the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) show that postoperative radiotherapy can reduce recurrence and breast cancer mortality in patients undergoing breast-conserving surgery or mastectomy with axillary lymph node dissection.
Advances in Medical Treatment
In 1999, the concept of “molecular subtyping of tumors” was first proposed. American biologist Charles M. Perou further refined this by classifying breast cancer based on expression profiles, ushering in the era of precision medicine in breast cancer treatment.
For HR+/HER2- breast cancer, the treatment has evolved from surgical treatment to endocrine therapy, and now to endocrine therapy combined with targeted therapies. For adjuvant treatment of high-risk early-stage patients, three strategies are typically used for intensification: extending endocrine therapy duration, combining with ovarian function suppression (OFS), or combining with CDK4/6 inhibitors. For low-risk early-stage patients, the use of multi-gene testing tools to aid in chemotherapy decisions is emphasized, with common tools including MammaPrint (70 genes), Oncotype DX (21 genes), and EndoPredict (12 genes). For late-stage HR+/HER2- breast cancer patients, treatment strategies are diverse: ET+CDK4/6 inhibitors, ET+HDAC inhibitors, ET+PI3K inhibitors, ET+AKT inhibitors, and ADC drugs, offering more treatment options. The publication of DB-04 study results for HER2-low expressing breast cancer patients has also made their treatment more precise.
For HER2-positive breast cancer patients, the treatment landscape has evolved significantly since the introduction of trastuzumab. Monoclonal antibodies, small molecule targeted drugs, and antibody-drug conjugates have collectively advanced the treatment of HER2-positive breast cancer. Early-stage HER2-positive breast cancer (neo)adjuvant treatment has shifted from a single model (chemotherapy combined with trastuzumab) to individualized treatment in the era of precision medicine (intensification for high-risk patients with dual-targeted therapy/T-DM1, and de-escalation for low-risk patients with anthracycline-free chemotherapy). HER2-targeted therapy has also significantly improved the survival of patients with advanced breast cancer.
For TNBC, molecular subtyping has greatly facilitated treatment, expanding options from initial chemotherapy to now include targeted and immunotherapies. TNBC patients now have a variety of adjuvant intensification treatments, significantly improving treatment outcomes.
Clinical Research Experience from the Cancer Hospital of the Chinese Academy of Medical Sciences
HR+ Breast Cancer
The DAWNA-1 study is a phase III trial of dalpiciclib, a domestically developed CDK4/6 inhibitor, in China. Interim analysis showed that dalpiciclib combined with fulvestrant significantly benefited patients in progression-free survival (PFS) compared to placebo combined with fulvestrant, supporting dalpiciclib as a new treatment option for HR+/HER2- advanced breast cancer patients who have relapsed or progressed after previous endocrine therapy. The results were presented at the 2021 ASCO Annual Meeting by Academician Binghe Xu and subsequently published in Nature Medicine.
The DAWNA-2 study is another multicenter, randomized, controlled phase III trial evaluating dalpiciclib combined with letrozole/anastrozole as first-line treatment for HR+/HER2- advanced breast cancer. The study showed significant clinical and statistical improvement in PFS regardless of menopausal status, supporting dalpiciclib as a new first-line treatment option for these patients.
The MIRACLE study is a national multicenter randomized phase II trial comparing letrozole alone with letrozole plus everolimus as first-line treatment for HR+/HER2- premenopausal women who have relapsed or metastasized after tamoxifen treatment. Results indicated that adding everolimus to letrozole significantly improved PFS in patients who failed tamoxifen treatment.
TNBC
Binghe Xu ‘s team conducted a small-sample randomized controlled trial for first-line treatment of advanced TNBC, showing that TP (paclitaxel plus platinum) was superior to TX (paclitaxel plus capecitabine). The CBCSG006 study, a multicenter phase III trial conducted with Fudan University Cancer Hospital and other institutions, established the importance of platinum-containing regimens for metastatic TNBC, with results published in Lancet Oncology. This led to the inclusion of platinum-based regimens as standard first-line treatment in German and Chinese breast cancer guidelines.
HER2-Positive Breast Cancer
Pyrrotinib, targeted at HER2-positive breast cancer, has undergone phase I-III studies, with results frequently presented at international conferences and published in high-impact journals. It became the first anti-tumor drug approved in China based on phase II clinical trial results under the new drug policy.
Translational Medicine Research
Experts at the Cancer Hospital of the Chinese Academy of Medical Sciences conducted research on new mechanisms of immunotherapy combined with chemotherapy for TNBC, with results published in Cancer Cell. Professor Leif W. Ellisen, Director of Breast Oncology at Massachusetts General Hospital Cancer Center, commented in Cancer Cell that this work represents the largest single-cell genomics study on the tumor microenvironment in TNBC, providing a reliable data foundation for understanding the spatial-temporal dynamics of TNBC and the interaction mechanisms in immunotherapy.
Additionally, scholars explored the biological mechanism of biomechanical forces from the extracellular matrix regulating stemness and quiescence in breast cancer cells and studied molecular markers predicting the efficacy of immunotherapy combined with anti-angiogenic drugs in TNBC. They collaborated with international peers to produce numerous research outcomes and will continue exploring predictive biomarkers, resistance mechanisms in targeted therapy, gene expression profiles in advanced patients, ongoing research in immunotherapy, the role of chemotherapy in enhancing immunotherapy, and the development of antibody-drug conjugates to contribute to breast cancer treatment.
Binghe Xu
- Academician of the Chinese Academy of Engineering, Member of the Chinese Academy of Medical Sciences
- Expert in Medical Oncology, Tenured Professor at Peking Union Medical College
- Director of the National Clinical Research Center for New Antitumor Drugs (GCP)
- Honorary Chairman of the Breast Cancer Professional Committee and Drug Clinical Research Professional Committee of the Chinese Anti-Cancer Association
- President of the Beijing Breast Disease Society and Beijing Oncology Society
