The 19th St. Gallen Breast Cancer Conference (SGBCC), held in Vienna from March 12 to 15, 2025, remains one of the most influential global platforms in early breast cancer care. Among seven studies awarded the prestigious Best Poster Award, four came from China, including a multi-center real-world study led by Professor Ying Fan from the Cancer Hospital Chinese Academy of Medical Sciences. Her research focused on treatment-insensitive HER2-positive breast cancer patients undergoing neoadjuvant therapy. Oncology Frontier spoke with Professor Fan to learn more about the study’s results, and broader implications.

Oncology Frontier: Congratulations on winning the Best Poster Award at SGBCC. What does this recognition mean to you?

Professor Ying Fan: Thank you. We were genuinely honored and a little surprised. The St. Gallen meeting is a global benchmark for clinical guidance in early breast cancer, so having our research recognized at this level was truly gratifying. It reflects the increasing international visibility of Chinese oncology research and reinforces our confidence in pursuing original studies—whether clinical, translational, or real-world. This kind of recognition motivates us to continue contributing meaningful insights to the global breast cancer community.

Oncology Frontier: Your team had three poster presentations at the conference. Could you walk us through the main themes of these studies, especially the one that received the award?

Professor Ying Fan: All three projects were inspired by observations from routine clinical practice—cases that raised questions we wanted to explore further. Each study was carried out by our graduate students, which also helped them develop solid scientific thinking grounded in real-world problems.

The award-winning study examined a subset of HER2-positive breast cancer patients who were insensitive to anti-HER2 therapy during neoadjuvant treatment. Although most HER2-positive patients respond well to targeted therapy, we consistently saw a small group—about 10 to 20 percent—who showed little or no response, often classified as disease progression or stable disease on imaging. In this study, we included over 500 patients from multiple centers and found that about 11 percent were insensitive to treatment.

What stood out about these patients was their tendency to present with more advanced disease, and many of them had triple-positive tumors or HER2 IHC 2+ expression—cases with greater biological heterogeneity. Moreover, some had received only single-agent anti-HER2 therapy, which appeared less effective than dual-targeted regimens. Using propensity score matching, we found that these non-responders had significantly worse prognoses, which clearly points to a need for better therapeutic strategies.

Based on this, we suggested possible approaches that could be explored in future trials, such as treatment escalation using antibody-drug conjugates like T-DXd, or for triple-positive cases, combining endocrine therapy with CDK4/6 inhibitors alongside anti-HER2 agents. While these ideas still need prospective validation, they offer a framework for thinking about treatment adaptation in this subset of patients.

We also reviewed how these patients were managed after their lack of response. Some switched to more intensive regimens, others maintained the original plan, and a portion moved directly to surgery. The variability in post-progression strategies reflects the uncertainty in this area—something we hope future research will help clarify.

The other two posters also addressed pressing questions in the neoadjuvant setting. One focused on patients who achieved pathologic complete response (pCR) in the breast but not in the lymph nodes, and vice versa. Although this discordance is relatively rare, it challenged the conventional belief that overall pCR is the main predictor of prognosis. We wanted to understand the biological and clinical distinctions between these patterns and what they might mean for long-term outcomes.

The third study looked at patients with N3 breast cancer, particularly those with lymph node involvement in less commonly discussed areas like the supraclavicular or internal mammary regions. These patients are often grouped as locally advanced disease, but we wondered whether the location of nodal spread might influence prognosis or response to treatment. This question is especially important for those whose nodal disease can’t be completely resected surgically, even after neoadjuvant therapy.

Ultimately, our aim was to shed light on real challenges that breast cancer clinicians face daily—issues that often fall outside the scope of traditional clinical trials. I think that’s also why the St. Gallen committee appreciated our work: it directly addressed unmet clinical needs with data that could eventually guide better decision-making in practice.

Oncology Frontier: What are the clinical implications of your study, and what directions do you see for future research?

Professor Ying Fan: At this stage, our findings are not yet ready to inform clinical practice directly, as this was an observational study based on real-world data. Further validation is essential. However, what we’ve observed clinically—and the patterns that emerged through our analysis—can serve as a valuable starting point for future research.

For instance, we identified a group of HER2-positive patients who showed poor response to anti-HER2 therapy. This raises fundamental questions about the underlying biological mechanisms: why does such heterogeneity exist among patients who, on the surface, share the same HER2-positive classification? We plan to revisit tumor specimens from these patients to explore whether certain tumor-suppressive pathways may be associated with the observed resistance. Even though clinical practice currently doesn’t involve anti-HER2 therapy for IHC 1+ patients, we believe there is a spectrum of HER2 expression that needs to be better understood. By quantifying this heterogeneity, we hope to clarify how it correlates with therapeutic outcomes.

In parallel, we’re preparing to conduct proteomic analyses to search for molecular markers that may help identify patients likely to be less responsive to standard treatment. These efforts could guide more refined, personalized therapeutic strategies in the future. As for treatment itself, there is currently no consensus on how to best manage patients who are insensitive to standard anti-HER2 regimens. Some clinicians opt to escalate treatment, while others switch to ADCs or pursue surgery. But which approach is truly optimal remains unknown.

To address this, we’re actively designing prospective, controlled studies. One area of focus is triple-positive breast cancer. We want to explore whether combinations such as chemotherapy plus anti-HER2 therapy or endocrine therapy plus CDK4/6 inhibitors and HER2-targeted agents can improve outcomes in this subgroup. These are the kinds of questions that will shape our research agenda moving forward.

Oncology Frontier: You’ve led many important studies in the field of medical oncology for breast cancer—some published in top journals, others selected for major conferences like ASCO, ESMO, and SGBCC. Could you share the most important lesson you’ve learned from these research experiences?

Professor Ying Fan: Taking this SGBCC study as an example, it may not appear particularly complex at first glance. It didn’t involve cutting-edge lab techniques or intricate data modeling. But it was born directly from clinical observation—real patients, real challenges.

That, I think, is the most valuable takeaway: clinical questions are everywhere. Many of them remain unanswered, hiding in plain sight. If we stay curious, remain thoughtful, and pay attention to what happens at the bedside, we can uncover important insights. Clinical research doesn’t always need to start with technology—it can start with a thoughtful question. And sometimes, that’s where the most meaningful research begins.

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Professor Ying Fan

Director of the Breast Oncology Ward, Department of Medical Oncology, Cancer Hospital Chinese Academy of Medical Sciences Chief Physician, Master’s Supervisor, PhD (Eight-Year Program, Peking Union Medical College) Visiting Scholar at the Royal Marsden Hospital/Institute of Cancer Research (UK), 2008–2009

• Deputy Chair and Secretary-General, Clinical Research Innovation and Development Committee, China Medical Education Association
• Deputy Chair, Youth Committee of the Beijing Breast Disease Prevention and Treatment Society
• Deputy Chair, Youth Committee of the Beijing Cancer Prevention and Treatment Research Association
• Deputy Chair, Breast Cancer Committee of the Beijing Association for Chronic Disease Prevention and Health Education
• Deputy Chair, Multidisciplinary Committee on Central Nervous System Metastases, Beijing Society of Integrative Medicine