The evolution of breast cancer diagnosis and treatment is an epic journey spanning past and present, marked by breakthroughs that have profoundly changed patient outcomes. From January 9 to 11, 2026, the Northern China Breast Cancer Salon · Annual Progress Review was held in Beijing. One of the most anticipated sessions was the Annual Review of Advances in Breast Cancer Therapy, which brought together leading experts to focus on the most significant international and domestic developments of 2025. Topics ranged from surgery, pathology, and radiotherapy to molecular classification and subtype-specific treatment, with in-depth discussion and synthesis of research that has reshaped clinical practice.To document the academic milestones of the past year, Oncology Frontier launched the “Breast Cancer Chronicle · Year 2025” series. During the Northern China Breast Cancer Salon · Annual Progress Review, we invited participating experts to review the major events in breast cancer research over the past year, learning from history while recording progress. In this installment, we invited Professor Shusen Wang of Sun Yat-sen University Cancer Center to review advances in endocrine therapy for HR+/HER2− advanced breast cancer.
Key Advances in Endocrine Therapy for HR+/HER2− Advanced Breast Cancer
The year 2025 marked a milestone in the history of breast cancer diagnosis and treatment. Not only were multiple new agents approved for breast cancer therapy, but numerous landmark clinical trial results were also presented at major academic conferences in China and internationally. These achievements have driven updates to clinical guidelines worldwide and provided patients with more effective treatment options. Below, I briefly summarize the advances in endocrine therapy for HR+/HER2− advanced breast cancer that I consider particularly noteworthy.
Inavolisib-Based Combination Therapy: A New First-Line Option
In October 2024, progression-free survival (PFS) results from the INAVO120 trial were reported, showing a median PFS of 15.0 months (95% CI: 11.3–20.5) in the inavolisib group compared with 7.3 months (95% CI: 5.6–9.3) in the placebo group (hazard ratio [HR] for disease progression or death, 0.43; 95% CI: 0.32–0.59; P < 0.001).
In March 2025, based on the INAVO120 results, the PI3Kα inhibitor inavolisib, in combination with palbociclib and fulvestrant, was approved by the National Medical Products Administration (NMPA) for first-line treatment of HR+/HER2− advanced breast cancer. This approval provides a more effective therapeutic option for patients with PIK3CA-mutant HR+/HER2− advanced breast cancer who have demonstrated resistance to prior endocrine therapy, including those who relapsed during or after adjuvant endocrine treatment.
At the 2025 ASCO Annual Meeting, updated PFS data from INAVO120 were presented, showing a median PFS of 17.2 months (95% CI: 11.6–22.2) in the inavolisib group versus 7.3 months (95% CI: 5.9–9.2) in the placebo group (HR 0.42; 95% CI: 0.32–0.55). Secondary endpoint analysis demonstrated a median overall survival (OS) of 34 months in the inavolisib group, representing a 7-month improvement over the placebo group (27 months), with a 33% reduction in the risk of death (HR 0.67, 95% CI: 0.48–0.94; P = 0.0190).
This triple-combination regimen has thus opened new avenues for first-line treatment of HR+/HER2− advanced breast cancer.
In addition, the INAVO123 trial is currently ongoing. This phase III, multicenter, randomized, double-blind, placebo-controlled study is evaluating inavolisib plus a CDK4/6 inhibitor (palbociclib) and letrozole versus placebo plus palbociclib and letrozole as first-line therapy for endocrine-sensitive, PIK3CA-mutant HR+/HER2− advanced breast cancer. The results of this study are eagerly anticipated.
Oral SERDs: New Directions Opened by the evERA BC Study
In the HR+/HER2− advanced breast cancer landscape, a range of novel agents is currently under investigation, with oral selective estrogen receptor degraders (SERDs) attracting particular attention. Throughout 2025, data from studies of oral SERDs continued to emerge.
At the 2025 ESMO Congress, results from the phase III evERA BC study (Abstract LBA16) were presented. This study demonstrated that giredestrant, an oral SERD, combined with everolimus, produced a statistically significant and clinically meaningful improvement in PFS compared with control therapy in patients previously treated with CDK4/6 inhibitors (8.77 vs 5.49 months; HR = 0.56), corresponding to a 44% reduction in the risk of disease progression or death.
The success of this combination opens a new therapeutic direction for oral SERDs in HR+/HER2− advanced breast cancer. Whereas previous studies primarily focused on oral SERDs as monotherapy or in combination with CDK4/6 inhibitors, this trial suggests that combining oral SERDs with mTOR inhibitors represents another promising strategy worthy of further exploration.
Conclusion
In summary, 2025 witnessed the entry of numerous landmark studies and novel agents into the field of breast cancer treatment. We look forward to the continuation of this positive trend, with more innovative therapies and optimized treatment concepts emerging in clinical practice to better serve patients with breast cancer.
Professor Shusen Wang Chief Specialist for Breast Cancer (Single-Disease Program) Sun Yat-sen University Cancer Center
