Editor's Note: From breaking through in later-line treatment to making advances in earlier lines, and from monotherapy to combination regimens that enhance efficacy, antibody-drug conjugates (ADCs) are reshaping the breast cancer treatment landscape. At the 2026 Annual Meeting of the American Society of Clinical Oncology (ASCO), several ADCs reported important clinical findings across multiple molecular subtypes, including HER2-positive and triple-negative breast cancer (TNBC), spanning the treatment continuum from later-line advanced disease to first-line therapy.As the 29th Annual Meeting of the Chinese Society of Clinical Oncology (CSCO) convenes, Oncology Frontier invited Professor Chunfang Hao of Tianjin Medical University Cancer Institute and Hospital to review the latest developments presented at ASCO and examine the expanding applications and emerging trends of ADCs in breast cancer, as well as their implications for evolving clinical practice.
Oncology Frontier: At the 2026 ASCO Annual Meeting, ADCs demonstrated encouraging results across different breast cancer subtypes and treatment settings. In TNBC, the ASCENT-04 study reported progression-free survival 2 (PFS2) and subsequent-treatment analyses, further supporting the role of sacituzumab govitecan (SG) plus pembrolizumab in first-line treatment for this population. In HER2-positive breast cancer, the DB-09 study presented analyses of treatment duration and clinical outcomes according to best response depth, while the DB-07 study reported its final analysis results. In addition, the novel EGFR × HER3 bispecific ADC iza-bren reported noteworthy findings.
Against this background, how do you view the trend toward expanding ADC use across breast cancer subtypes, from later-line to first-line treatment and from monotherapy to combination regimens?
Professor Chunfang Hao: ADCs are among the most closely watched therapeutic classes in breast cancer in recent years. They have driven major breakthroughs in the treatment of different molecular subtypes and represent a milestone in the field. For example, the emergence of HER2-targeted ADCs has not only expanded treatment options for HER2-positive breast cancer but also established HER2-low disease as a new therapeutic category, challenging the boundaries of traditional molecular classification.
From a drug-development perspective, ADCs have generally followed the classic pathway for anticancer drug development: beginning in later-line treatment of advanced disease, moving progressively into earlier-line settings, and then extending into early-stage disease, including neoadjuvant therapy and adjuvant treatment intensification. Compared with traditional novel agents, ADCs have advanced through this development pathway considerably faster.
Trastuzumab deruxtecan (T-DXd), for example, is a HER2-targeted ADC that achieved landmark efficacy breakthroughs in later-line and second-line treatment, enabling its rapid development in the first-line setting. Other ADCs have followed a similar development strategy. As a result, recent international oncology meetings have seen a steady stream of Phase III trial results for different ADCs.
During the initial stages of development, ADCs are generally evaluated as monotherapies against existing standard treatments. To date, ADC monotherapy has demonstrated superiority over established standard treatments in both later-line TNBC and second-line HER2-positive breast cancer, establishing these agents as standards of care in the respective settings.
Building on these achievements, combination therapy has become a major avenue for further improving efficacy. ADCs already combine targeted drug delivery with a cytotoxic payload. Provided that the resulting adverse effects remain manageable, combining ADCs with other therapies may yield greater efficacy and help identify patient populations most likely to benefit.
The ASCENT-04 study exemplifies this approach in first-line TNBC. The results showed that, among patients eligible for combination immunotherapy, a Trop-2-targeted ADC combined with immunotherapy provided greater progression-free survival (PFS) benefit than the current standard regimen of chemotherapy plus immunotherapy, with an advantage in survival outcomes also reported. These findings are expected to influence clinical practice and represent an important evidence-based advance in first-line TNBC treatment.
A similar development strategy is being pursued in HER2-positive breast cancer. Although T-DXd monotherapy has already demonstrated outstanding efficacy, researchers continue to investigate more effective combination regimens for first-line treatment. The DB-09 study showed that T-DXd plus pertuzumab in first-line HER2-positive advanced breast cancer could increase PFS from the current range of approximately 18–24 months to more than 40 months—a striking improvement in efficacy. Following these groundbreaking results, both international and Chinese clinical guidelines were rapidly updated to include the regimen, changing the first-line treatment landscape for HER2-positive advanced breast cancer.
In recent years, Chinese innovative drug developers have made rapid progress in ADC research, with encouraging clinical results. Iza-bren, a novel bispecific ADC reported at this year’s meeting, demonstrated promising efficacy as a monotherapy compared with chemotherapy in later-line advanced TNBC. Based on established drug-development patterns, it may also be explored in combination regimens in the future. The evolution from single-target ADCs to bispecific ADCs itself reflects a design philosophy that seeks to engage multiple targets within a single therapeutic construct.
It is worth noting that although an increasing number of ADCs are being investigated in early-stage breast cancer, particularly in neoadjuvant and adjuvant settings, the results reported to date have not been consistent across studies. In clinical practice, treatment decisions must therefore continue to be guided by evidence-based medicine, with regimens selected according to the characteristics of individual patients and the populations most likely to benefit. This is essential to ensure that patients receive the most appropriate treatment at every stage of their disease.
In addition, novel ADCs have adverse-event profiles that differ from those of conventional chemotherapy, making careful safety management essential. ADC combination strategies are also prompting new questions about treatment duration and intensity: should combination therapy continue throughout the entire treatment course, or should selected patients who respond well undergo treatment de-escalation and transition to maintenance therapy? These are active areas of research, and the emerging evidence warrants close attention.
Professor Chunfang Hao
