Editor's Note: The 29th CSCO Academic Annual Meeting, jointly organized by the Chinese Society of Clinical Oncology (CSCO) and the Beijing Xisike Clinical Oncology Research Foundation, was grandly opened in Jinan, Shandong Province, from September 17 to 19, 2026. With the theme “Upholding Standards and Advancing Digital and Intelligent Innovation,” the annual meeting continued CSCO's longstanding mission of bringing together renowned oncology experts and scholars from around the world to share cutting-edge research findings and clinical experience. The meeting is expected to further advance cancer diagnosis and treatment in China and worldwide.At this year’s meeting, Professor William Gradishar of Northwestern University’s Feinberg School of Medicine joined Oncology Frontier for an exclusive interview, sharing his insights on “The Evolution and Future of HER2-Positive Breast Cancer Treatment: The Foundation of Dual HER2 Blockade and the Rise of ADCs.”
Oncology Frontier: HER2-positive breast cancer is the most mature and fastest-evolving field of precision breast cancer therapy, with the treatment landscape continuously reshaped over the past decade—from single-target to dual-target blockade and now the ADC era. How would you characterize the current treatment landscape of HER2-positive breast cancer?
William Gradishar: HER2-positive breast cancer is a highly aggressive subtype. Before the advent of trastuzumab, the prognosis was extremely poor, with virtually no effective treatment options. With the introduction of HER2-directed therapy, the outlook and prognosis of patients with metastatic disease changed dramatically. Subsequently, dual HER2-targeting—such as trastuzumab plus pertuzumab with chemotherapy—further improved patient outcomes, and this strategy has been extended from metastatic treatment to the neoadjuvant and adjuvant settings.
Over the past 5 to 8 years, the introduction of antibody-drug conjugates (ADCs) has marked another major leap forward. These agents combine HER2-directed therapy with cytotoxic drugs, further enhancing outcomes in both early-stage and advanced disease. We have witnessed the evolution from “trastuzumab plus a single chemotherapy agent” to “doublet chemotherapy plus dual HER2 blockade,” and now ADCs—whether T-DXd monotherapy or in combination with pertuzumab—are reshaping the treatment landscape. Each iteration has delivered dual improvements in outcomes for both early-stage and advanced disease.
Oncology Frontier: HP dual blockade plus chemotherapy has long been the cornerstone of HER2-positive breast cancer treatment. TQB2102, a bispecific ADC that covers both the trastuzumab and pertuzumab binding sites, has achieved neoadjuvant response rates exceeding those historically reported with HP dual blockade plus chemotherapy, with multiple phase III studies underway. In your view, how will these results affect the position of the HP regimen in the treatment of HER2-positive breast cancer?
William Gradishar: If novel agents, particularly bispecific antibodies targeting different domains of HER2, prove more effective than the HP regimen or even T-DXd, these drugs may ultimately replace current therapies. The chemotherapy plus trastuzumab and pertuzumab regimen established by CLEOPATRA served as the standard of care for over a decade and was widely used globally in patients with advanced disease, and was even extended to the neoadjuvant and early-stage settings. Today, ADCs have demonstrated superior efficacy in both advanced and early-stage disease. Taking TQB2102 as an example, its neoadjuvant monotherapy study showed a tpCR rate of 76.9% with the 8-cycle 6.0 mg/kg regimen, and a tpCR rate of 73.2% in the HER2 3+ population—numerically superior to historical reports for prior ADCs and standard HP plus chemotherapy. If such bispecific antibodies prove to have superior efficacy and manageable side effects, they will ultimately replace current treatments, representing a significant advance in the field of HER2-positive breast cancer.
Oncology Frontier: In recent years, we have seen a rapid emergence of global clinical research and innovative drugs, which have brought more treatment options and hope to patients with HER2-positive breast cancer. In first-line treatment for advanced disease, the CLEOPATRA study established the THP regimen as the backbone of therapy for over a decade. China-developed trastuzumab, pertuzumab, and other biosimilar agents have also provided patients with new options that are equivalent and more accessible. Studies such as PATINA, HER2CLIMB-05, and DESTINY-Breast09 have since reported impressive results in the advanced first-line setting. How do you view these new treatment approaches? And in clinical practice, how do you select individualized treatment strategies for patients in the first-line advanced setting?
William Gradishar: The first-line metastatic landscape is evolving from a single cornerstone to multiple coexisting options. The THP regimen established by CLEOPATRA has served as the cornerstone for over a decade, accumulating long-term efficacy and safety experience; in 2024–2025, studies such as PATINA, HER2CLIMB-05, and DESTINY-Breast09 have provided new options for first-line treatment, forming a landscape where multiple regimens coexist.
The PATINA study adopts an “induction + maintenance” design, adding the CDK4/6 inhibitor palbociclib after induction therapy, extending median PFS from 29.1 months to 44.3 months—an improvement of more than 15 months—making it the first phase III study to demonstrate clinical benefit of a CDK4/6 inhibitor in HR+/HER2+ metastatic breast cancer. The HER2CLIMB-05 study similarly adopts a maintenance design, adding tucatinib to trastuzumab + pertuzumab maintenance, extending median PFS from 16.3 months to 24.9 months, with a 36% reduction in the risk of disease progression or death. The DESTINY-Breast09 study directly challenges the first-line standard, evaluating T-DXd plus pertuzumab versus THP.
These studies suggest that first-line treatment is evolving from fixed cycles toward long-term management, emphasizing maintenance therapy to prolong disease control after induction. In a landscape with multiple coexisting options, regimen selection requires comprehensive consideration of prior treatment history, brain metastasis status, biomarker characteristics, cardiotoxicity risk, patient preference, and drug accessibility to develop individualized treatment strategies.
Professor William Gradishar
