Editor’s Note Spotlight on SABCS, insights delivered in real time. The 48th San Antonio Breast Cancer Symposium (SABCS) was held from December 9 to 12, 2025, in San Antonio, USA, bringing together cutting-edge research findings and clinical insights from the global breast cancer community. To efficiently convey the key messages of the meeting, this edition of Insight Broadcast invited Professor Jin Yang from the First Affiliated Hospital of Xi’an Jiaotong University as the on-site expert commentator. Drawing on two pivotal studies—ASCENT-07 and lidERA—Professor Yang interprets the latest advances and challenges in first-line treatment of advanced disease and adjuvant therapy in early-stage HR+/HER2− breast cancer, while exploring the evolving treatment paradigm and future directions.01
ASCENT-07 Study: Sacituzumab Govitecan Fails to Meet the Primary Endpoint as First-Line Chemotherapy in HR+/HER2− Advanced Breast Cancer
Professor Jin Yang: The first oral presentation I would like to discuss is the ASCENT-07 study. Patients with endocrine-resistant HR+/HER2− advanced breast cancer have a poor prognosis, with limited options for first-line chemotherapy. The Trop-2–targeting antibody–drug conjugate (ADC) sacituzumab govitecan (SG) has already demonstrated superiority over chemotherapy in later-line treatment in the TROPiCS-02 study. The key question ASCENT-07 sought to answer was whether SG could be moved forward to replace chemotherapy in the first-line setting.
This randomized phase III study evaluated the efficacy and safety of SG versus treatment of physician’s choice chemotherapy (TPC) in patients with HR+/HER2− advanced breast cancer who were resistant to prior endocrine therapy and considered suitable for first-line chemotherapy.
A total of 690 patients were enrolled. More than 90% had previously received CDK4/6 inhibitors, and approximately 70% had liver metastases, indicating a high tumor burden. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review (BICR).
There was considerable anticipation for this study, particularly given the success of DESTINY-Breast06, which showed that trastuzumab deruxtecan (T-DXd) significantly prolonged PFS compared with investigator’s choice chemotherapy in pretreated endocrine-resistant HR+/HER2-low advanced breast cancer. Unfortunately, ASCENT-07 did not meet its primary endpoint. After a median follow-up of 15.4 months, median PFS was identical in both arms at 8.3 months, with no statistically significant difference. However, trends favoring SG were observed in investigator-assessed PFS and immature overall survival (OS) data (investigator-assessed PFS HR = 0.78; OS HR = 0.72). Duration of response (DoR) was also longer in the SG arm (12.1 months vs 9.3 months).
In terms of safety, grade ≥3 neutropenia was more frequent in the SG arm (56% vs 21%), but dose-reduction rates were similar between groups. Treatment discontinuation was lower with SG, and no new safety signals were identified.
The discrepancy between BICR and investigator-assessed PFS warrants reflection. BICR strictly adheres to RECIST v1.1 criteria, whereas investigators may integrate clinical symptoms into their judgment and distinguish treatment interruption due to toxicity from true disease progression. Overestimation of the expected effect size of SG may also have contributed to insufficient statistical power.
These results suggest that in the first-line setting after endocrine resistance in HR+/HER2− advanced breast cancer, not all ADCs can outperform chemotherapy in the way T-DXd did in DESTINY-Breast06. Target selection is critical. Importantly, this is not the end of the road for SG. We still await subgroup analyses based on Trop-2 expression and more mature OS data, and must further optimize management of hematologic toxicity—particularly neutropenia, which reached 56% at grade ≥3 in this study. Precision patient selection remains the key to the success of ADC therapy.
Study Overview: ASCENT-07
Abstract No.: GS1-09 Title: Primary results of ASCENT-07: Sacituzumab govitecan versus chemotherapy in HR+/HER2− (IHC 0, 1+, 2+/ISH−) metastatic breast cancer after endocrine therapy
Background
Patients with endocrine-resistant HR+/HER2− metastatic breast cancer (mBC) typically have poor outcomes, characterized by short PFS and low OS, with limited treatment options. The phase III TROPiCS-02 trial demonstrated that SG significantly improved PFS and OS compared with chemotherapy in patients previously treated with chemotherapy. ASCENT-07 reports the primary results of a randomized phase III trial enrolling adults with HR+/HER2− unresectable locally advanced or metastatic breast cancer who had received prior endocrine therapy and were eligible for first-line chemotherapy.
Methods
Patients were randomized 2:1 to receive SG (10 mg/kg IV) or physician’s choice chemotherapy (TPC: capecitabine, nab-paclitaxel, or paclitaxel). Stratification factors included prior duration of CDK4/6 inhibitor use in the metastatic setting, HER2 IHC status, and disease distribution. The primary endpoint was BICR-assessed PFS per RECIST v1.1. Key secondary endpoints included OS, BICR-assessed objective response rate (ORR), and quality of life.
Results
A total of 690 patients were randomized (456 to SG, 234 to TPC). Median age was 57 years. Over 90% had prior CDK4/6 inhibitor exposure. Median PFS was 8.3 months in both arms (HR = 0.85; 95% CI: 0.69–1.05; P = 0.130). Investigator-assessed PFS favored SG (HR = 0.78; P = 0.008). OS data were immature but showed an early favorable trend (HR = 0.72; P = 0.029). Median DoR was longer with SG (12.1 vs 9.3 months). Grade ≥3 neutropenia was more frequent with SG, but discontinuation rates were lower.
Conclusion
SG did not demonstrate a statistically significant PFS benefit over chemotherapy as first-line treatment after endocrine therapy in HR+/HER2− advanced breast cancer. However, early trends toward improvement in OS and DoR were observed, with no new safety concerns.
02
lidERA Study: Twenty Years in the Making—Oral SERD Giredestrant Opens a New Chapter in Adjuvant Therapy for Early Breast Cancer
Professor Jin Yang: The second landmark study is lidERA. This is the first phase III trial in more than 20 years—since aromatase inhibitors became standard—to demonstrate a positive result for a novel endocrine therapy in the adjuvant treatment of early-stage HR+/HER2− breast cancer. When the positive results were presented at SABCS, the audience responded with prolonged applause, reflecting both anticipation and recognition of a true breakthrough.
The study enrolled 4,170 patients with stage I–III disease, randomized to receive the oral selective estrogen receptor degrader (SERD) giredestrant or standard endocrine therapy (tamoxifen or an aromatase inhibitor) for five years. More than 70% of patients had stage II–III disease, and 75% had lymph-node involvement, representing a population at intermediate to high risk of recurrence.
After a median follow-up of 32.3 months, the primary endpoint was met. Giredestrant significantly improved invasive disease-free survival (iDFS), reducing the risk of disease progression or death by 30%. Three-year iDFS rates were 92.4% versus 89.6%. Distant recurrence-free interval (DRFI) was also significantly improved, with a 31% reduction in distant recurrence risk. OS showed a favorable trend.
The safety profile was favorable. The most common adverse events were arthralgia and hot flashes, consistent with known SERD characteristics. Treatment discontinuation due to adverse events was actually lower in the giredestrant group than in the standard therapy group (5.3% vs 8.2%).
These results sparked extensive discussion, centered on three key questions.
First, how will clinical practice change? The study population largely overlaps with patients currently considered for adjuvant CDK4/6 inhibitor intensification. Two potential scenarios emerge:
- For high-risk patients who have completed 2–3 years of CDK4/6 inhibitor therapy, switching to giredestrant to complete adjuvant endocrine treatment may be an option.
- For intermediate-risk patients who do not require CDK4/6 inhibitors, giredestrant may directly replace aromatase inhibitors as a superior option.
Second, why is giredestrant effective in the overall early-stage population, whereas ESR1 mutation status is critical in advanced disease? The answer lies in the comparator. In advanced disease, oral SERDs are compared with fulvestrant—another estrogen receptor degrader—making ESR1 mutation a key predictive marker. In early disease, the comparator is tamoxifen or aromatase inhibitors. Prior studies such as FALCON and FIRST have already shown fulvestrant to be superior to aromatase inhibitors, providing a strong biological rationale for the observed benefit. Early-stage disease is characterized by low tumor burden and a very low ESR1 mutation rate, likely representing the optimal setting for SERDs.
Third, accessibility and future exploration. Oral SERDs are expensive, and the financial burden of five years of adjuvant therapy is a real concern. Future research directions include ctDNA-guided strategies for switching from AI to SERD, as well as combination adjuvant therapy with SERDs and CDK4/6 inhibitors.
In summary, the lidERA study is poised to redefine adjuvant endocrine therapy for HR+/HER2− early breast cancer, offering patients a potentially more effective and well-tolerated option.
Study Overview: lidERA
Abstract No.: GS1-10 Title: Giredestrant versus standard endocrine therapy as adjuvant treatment in estrogen receptor–positive, HER2-negative early breast cancer: Results from the global phase III lidERA study
Conclusion The lidERA trial is the first study since the early 2000s to demonstrate that a novel endocrine therapy improves outcomes in early breast cancer. Giredestrant significantly improved iDFS (HR 0.70; 95% CI: 0.57–0.87; P = 0.0014) and DRFI, with a favorable safety profile, supporting its potential role as a new standard adjuvant therapy for HR+/HER2− early breast cancer.
Summary
These two studies highlight contrasting challenges and breakthroughs in HR+/HER2− breast cancer across disease stages. ASCENT-07 underscores that not all ADCs can successfully replace chemotherapy in the first-line advanced setting, reinforcing the importance of target selection and precision stratification. In contrast, lidERA represents a milestone success, breaking a two-decade stalemate in adjuvant endocrine therapy and offering a powerful new option for patients with early-stage disease. Together, they point to a future in which treatment of advanced disease must become increasingly precise, while early-stage treatment can be increasingly potent.
Professor Jin Yang
MD, Chief Physician / Professor, Doctoral Supervisor Director, Cancer Center The First Affiliated Hospital of Xi’an Jiaotong University
