Editor’s Note: Triple-negative breast cancer (TNBC) is a highly aggressive and heterogeneous subtype of breast cancer, accounting for 15% to 20% of all breast cancers. Compared to other subtypes, TNBC patients often experience rapid clinical progression, are diagnosed at a younger age, have faster distant recurrence, and more common visceral metastasis. Treatment for TNBC is usually limited to chemotherapy, resulting in a poorer prognosis. With the breakthroughs in immune checkpoint inhibitors in the field of oncology, TNBC, as a relatively “hot” subtype among the otherwise immune “cold” tumors, has become a focus of research, showing improved therapeutic effects. Furthermore, neoadjuvant treatment, as a pre-surgical intervention for breast cancer, which aims to “downstage and conserve the breast” and acts as “in vivo drug sensitivity testing,” has also received considerable attention in recent years. At the 2023 COMB conference, Professor Qiao Li from the Cancer Hospital of the Chinese Academy of Medical Sciences reviewed the current state and future of TNBC neoadjuvant research. Subsequently, the “Oncology Frontier” magazine invited Professor Li to discuss the progress and future directions of TNBC neoadjuvant treatment.
Oncology Frontier: Given the strong heterogeneity of TNBC, for which patient groups is neoadjuvant treatment suitable?
Professor Qiao Li: Triple-negative breast cancer exhibits strong heterogeneity, and there are no precise therapeutic targets available clinically. In recent years, the group eligible for neoadjuvant treatment in this subtype has been expanding. Neoadjuvant treatment is the preferred option for patients with locally advanced disease, and is also suitable for patients who require downstaging for breast conservation. Moreover, neoadjuvant treatment has been extended to some stage II TNBC patients, including those with T2 or N1 cancer, and even some studies have included patients with T1cN0 cancer. However, whether stage I patients should receive neoadjuvant treatment is still a matter of debate.
Oncology Frontier: At the 2023 ESMO conference, the 5-year EFS results from the KEYNOTE-522 study were published. Could you please share how these results will impact the treatment of early-stage TNBC patients?
Professor Qiao Li: The KEYNOTE-522 study has undergone several interim analyses, and at the 2023 ESMO conference, the sixth pre-specified interim analysis of EFS was updated. In this analysis, we continued to see further benefits in the 5-year EFS rate for the pembrolizumab group, with a 9% difference between groups (81.3% vs. 72.3%), compared to the 7.7% difference reported in the fourth interim analysis (84.5% vs. 76.8%). The patients’ benefits have continued to expand. The significance of the KEYNOTE-522 study lies in the fact that not only did the treatment group achieve a significant increase in the near-term efficacy rate of pCR, but the 5-year EFS rate also increased compared to the three-year follow-up results. With a median follow-up of 63.1 months, there were 145 events (18.5%) in the pembrolizumab group and 108 events (27.7%) in the chemotherapy-only group, maintaining a hazard ratio (HR) of 0.63.
The recent efficacy and long-term survival data from this study provide further evidence and justification for the neoadjuvant strategy of combining immunotherapy with chemotherapy for early-stage TNBC patients. It is important to note that in future clinical practice, it is still necessary to refer to the study population included in clinical research, specifically the entry criteria emphasized in the KEYNOTE-522 study, which focuses on early-stage N0-N2, PD-L1 highly expressive patients.
Oncology Frontier: At this year’s COMB conference, you presented a lecture on “Neoadjuvant Inventory in TNBC.” Looking back at 2023, what other research in the neoadjuvant treatment field for TNBC has impressed you?
Professor Qiao Li: In addition to the KEYNOTE-522 study, there have been other studies in 2023 that have opened new avenues in the neoadjuvant immunotherapy of triple-negative breast cancer, including the IMpassion031, NeoTRIP, and GeparNUEVO studies. Some studies did not achieve ideal survival outcomes but conducted exploratory analyses of biomarkers during the early neoadjuvant phase of immunotherapy for TNBC. Biomarker analyses also revealed that the tumor microenvironment and immune profiling of TNBC can affect the benefits and efficacy of immunotherapy, with immune-related biomarkers showing a positive correlation with treatment outcomes. Researchers in China are also conducting studies on the predictive efficacy of immunotherapy-related biomarkers. Additionally, a significant proportion of TNBC patients have BRCA mutations or are in a homologous recombination deficiency (HRD) state. Therefore, in future TNBC treatments, PARP inhibitors may hold more exploratory value for selected populations.
Furthermore, drugs currently used in the late stages may also be explored in neoadjuvant treatments for TNBC in the future, such as new ADC drugs targeting Trop-2 and HER2, which may be used in combination with immunotherapy. I believe that in the future, we will have more options for treating early-stage TNBC.
Qiao Li
Associate Chief Physician, Master’s Supervisor
Cancer Hospital, Chinese Academy of Medical Sciences, Department of Internal Medicine
Vice Chair of the Youth Committee of the Breast Cancer Professional Committee, Chinese Research Hospital Association
Standing Member and Secretary-General, Breast Cancer Committee, Chinese Primary Health Care Foundation
Secretary-General, Health Management Committee, Beijing Breast Disease Prevention and Treatment Association
Chairperson, Breast Cancer Prevention and Treatment Expert Committee, Beijing Health Promotion Association
Vice Chair of the Youth Academic Committee, Beijing Breast Disease Prevention and Treatment Association
Standing Committee Member and Youth Committee Chair, Breast Cancer Integrated Prevention and Treatment Committee, Beijing Association for Prevention and Treatment of Chronic Diseases of Integrated Traditional Chinese and Western Medicine
Editorial Roles:
Editorial Board Member, JCO Chinese Edition, CANCER Chinese Edition, Chinese Journal of Breast Disease (Electronic Edition), Journal of Clinical and Pathology, and Frontiers of Medicine in China
