Editor’s Note: The 2025 American Society of Clinical Oncology (ASCO) Annual Meeting took place from May 30 to June 3 in Chicago. At this global event, Professor Yiding Chen from the Second Affiliated Hospital, Zhejiang University School of Medicine, presented results from the biomarker analysis of the DANCER study. Focusing on operable HER2-negative Luminal B breast cancer, the study explored biomarkers related to neoadjuvant dalpiciclib-based therapy, offering new perspectives for precision treatment. Oncology Frontier conducted an exclusive interview with Prof. Chen onsite at ASCO, where he detailed the background, findings, and clinical significance of the study—highlighting the crucial role biomarkers may play in predicting treatment response and opening new avenues for breast cancer care.Expert Interview
Oncology Frontier: Could you briefly introduce the rationale behind the DANCER study and the key findings presented at this year’s ASCO?
Prof. Yiding Chen: At this year’s ASCO Annual Meeting, our team presented data from the DANCER study as a poster (Abstract #600). In the field of neoadjuvant therapy for breast cancer, especially for HR+/HER2– (Luminal B) patients, we continue to face many challenges. The efficacy of both neoadjuvant chemotherapy and neoadjuvant endocrine therapy has been suboptimal. While trials like CheckMate 7FL and KEYNOTE-756 have shown that combining nivolumab or pembrolizumab with neoadjuvant chemotherapy can achieve a pathological complete response (pCR) rate of about 25%, neoadjuvant strategies for Luminal B patients remain problematic, particularly in China.
To address this, we designed a small, single-arm clinical study called DANCER. It’s a phase II, single-arm trial guided by circulating tumor DNA (ctDNA) to evaluate the clinical activity of dalpiciclib combined with an aromatase inhibitor as a neoadjuvant treatment for operable HER2-negative Luminal B breast cancer.
We found that two weeks after initiating treatment (T1), 86.7% of patients (26/30) achieved complete cell cycle arrest (CCCA), which was our primary endpoint. This is a very promising result for neoadjuvant endocrine therapy in Luminal B breast cancer. However, we still observed suboptimal clinical responses in a subset of patients.
There are limitations to our study—for instance, the pCR rate was not high, and the proportion of patients achieving RCB 0 or RCB 1 was also relatively low. To further investigate, we conducted translational research and found that biomarkers such as ctDNA could better indicate how patients are responding to treatment. When grouping patients by RCB 0 or RCB 1, the number of cases is limited. But if we classify patients based on ctDNA-guided response, we might be able to predict outcomes at a much earlier stage—allowing us to better evaluate treatment efficacy.
During the ASCO poster session, international scholars engaged in discussion with us. One of the main questions was about long-term follow-up results, given the high CCCA rate observed, which implies favorable prognosis. We responded that the follow-up is ongoing. However, we are hopeful that, through continuous ctDNA monitoring, we can identify patients who benefit from neoadjuvant therapy early on—and perhaps even spare them from further adjuvant intensification.
The DANCER study serves as a meaningful starting point among related clinical trials. Our ultimate goal is to guide neoadjuvant treatment in Luminal breast cancer through biomarkers like ctDNA. We also hope this approach will help more patients benefit from chemotherapy-free regimens and lead to better prognoses for this population.
Oncology Frontier: Despite the high CCCA rate observed in the DANCER study, a subset of patients still showed poor clinical responses. Does this reflect the broader issue of heterogeneity in breast cancer treatment? How can deeper molecular subtyping and biomarker research help optimize treatment selection?
Professor Yiding Chen: Indeed, in the DANCER study, we observed an excellent CCCA (complete cell cycle arrest) rate at the two-week mark. However, the proportion of patients who ultimately achieved pCR or RCB 0 was still very low, which drew our serious attention. It is well known that biomarkers play a crucial role in predicting prognosis. At this year’s meeting, multiple studies on ctDNA and translational research were presented. These studies suggest that in HER2-negative breast cancer, patients with persistently negative ctDNA—even if they do not achieve pCR—can still have favorable prognoses. This finding further highlights the importance of biomarker testing. By utilizing such tools, we hope to more accurately identify patients whose tumors can be effectively suppressed with relatively simple treatment strategies, thereby improving therapeutic outcomes and prolonging survival.
Oncology Frontier: Do the results of the DANCER study suggest a shift in breast cancer treatment from a traditional “one-size-fits-all” approach toward more precise, individualized strategies? What broader implications could this transformation have for clinical practice, resource allocation, and patient quality of life?
Professor Yiding Chen: Breast cancer is among the most heterogeneous of all cancer types. This is precisely why we continue to face challenges and seek better treatment options for HER2-positive, triple-negative, and Luminal subtypes. Given this heterogeneity, accurate patient assessment and diagnostic testing are absolutely essential in clinical care.
In the neoadjuvant treatment of Luminal B breast cancer, we have successfully identified patients with persistently negative ctDNA and treated them with endocrine therapy plus CDK4/6 inhibitors. If these patients continue to show favorable outcomes during follow-up, I believe this would signify a major step toward achieving our ultimate goal of highly precise treatment. In our clinical studies, even patients who did not achieve pCR often opted out of adjuvant chemotherapy. We respect their choices and hope that long-term follow-up will reveal positive prognoses for these individuals.
Currently, for breast cancer subtypes with significant heterogeneity, we are still actively exploring how to implement truly personalized therapy. While classification methods have improved, they may still fall short of addressing every patient’s needs. Nonetheless, we firmly believe that by combining individualized treatment with tools like biomarker and ctDNA testing, we will ultimately overcome these challenges—delivering better prognoses and improved quality of life for more patients.
Study Overview
Study Title: Biomarkers of neoadjuvant dalpiciclib in patients with operable HER2-negative luminal B breast cancer in the DANCER trial
Background: DANCER (NCT05640778) was a circulating tumor DNA (ctDNA)-directed, single-arm, phase II trial investigating the clinical activity of dalpiciclib combined with aromatase inhibitors as a neoadjuvant regimen for operable human epidermal growth factor receptor 2 (HER2)-negative luminal B breast cancer. Although a high complete cell cycle arrest (CCCA) rate (primary endpoint) of 86.7% (26/30) was achieved at 2 weeks (T1), some patients showed suboptimal clinical responses after neoadjuvant therapy. This underscores the importance of identifying biomarkers predictive of response to CDK4/6 inhibitors.
Methods: The study collected plasma samples at baseline (T0), T1, mid-treatment (T2), surgery (S), and post-operation (PO) for ctDNA and Olink proteomic analysis. Tumor tissues collected at T0, T1, and S were subjected to somatic mutation analysis, immunohistochemistry, and MammaPrint index evaluation. Patients who achieved CCCA at both T1 and S, and showed objective radiographic response by MRI at S, were classified as good responders (GRs, n=15); all others were categorized as moderate responders (MRs, n=15).
Results showed balanced baseline clinicopathological characteristics between GRs and MRs. Compared to MRs, GRs demonstrated significantly lower residual cancer burden (RCB) scores, lower preoperative endocrine prognostic index (PEPI) scores, lower histological tumor grade, Ki-67 expression, and CA15-3 levels at surgery. Additionally, GRs had significantly higher Miller-Payne grades, levels of tumor-infiltrating lymphocytes, and tumor shrinkage rates.
Biomarker Findings: GRs showed higher ctDNA clearance rates at or before T2 (100.0% vs. 54.5%; P=0.045), higher plasma levels of CCL4 (P=0.029) and CCL19 (P=0.020), and increased immunohistochemical expression of pRb (P=0.044) and CDK4 (P=0.034).
Moreover, significant changes in copy number variations of GSTM1 were observed at surgery: five deletions detected at baseline were no longer present, while five new amplifications emerged (P=0.007). Early failure to clear ctDNA was significantly associated with RCB class III and PEPI score ≥4. In addition, MammaPrint high-risk patients had significantly higher RCB and PEPI scores compared to low-risk patients.
Study Conclusion
In patients with operable HER2-negative luminal B breast cancer, those who exhibit early ctDNA clearance, a low-risk MammaPrint profile, GSTM1 deletion, increased expression of pRb/CDK4, and elevated plasma levels of CCL4 and CCL19 may derive significant benefit from neoadjuvant treatment with dalpiciclib.
Professor Yiding Chen
the Second Affiliated Hospital, Zhejiang University School of Medicine
