Editor’s Note: The 2026 National Breast Cancer Conference was held in Beijing from April 10–12, during which the Chinese Society of Clinical Oncology (CSCO) Breast Cancer Guidelines 2026 (CSCO BC Guidelines 2026) underwent major updates. At the meeting, Professor Chunfang Hao from Tianjin Medical University Cancer Institute and Hospital delivered a comprehensive overview of the latest advances in the management of HR-positive breast cancer.Oncology Frontier invited Professor Hao to provide an in-depth interpretation of the updated recommendations for HR-positive advanced breast cancer in the 2026 CSCO BC Guidelines, including the supporting clinical evidence, implications for real-world practice, ongoing unmet clinical needs, and future directions in treatment development.
01
Oncology Frontier: The 2026 edition of the CSCO BC Guidelines was officially released during this year’s National Breast Cancer Conference. Compared with the 2025 edition, what major updates were introduced for the management of HR-positive advanced breast cancer?
Professor Chunfang Hao: As anticipated each April, we welcomed the annual update of the CSCO BC Guidelines. I will focus specifically on the updates related to salvage endocrine therapy for patients with HR-positive advanced breast cancer.
In the 2026 edition, Category I recommendations across all patient subgroups continue to include CDK4/6 inhibitors combined with either aromatase inhibitors (AIs) or fulvestrant.
The most significant changes involve two major patient stratification groups.
First, in patients with tamoxifen-resistant or AI-resistant disease, the regimen of inavolisib plus palbociclib plus fulvestrant (Level 1B evidence) has been upgraded from a previous Category II recommendation to a Category I recommendation with Level 1A evidence. This adjustment was driven by the results of the INAVO120 study, regulatory approval of the indication, and inclusion of the regimen in the national reimbursement system.
Second, in patients with AI-resistant disease and those who progressed after CDK4/6 inhibitor therapy, capivasertib plus fulvestrant (Level 1B evidence), previously listed as a Category III recommendation, has now been upgraded to a Category I recommendation based on the CAPItello-291 study and regulatory approval of the corresponding indication.
As a result of these updates, Category I recommendations now offer multiple treatment options for different patient subgroups.
For broad patient populations without genomic testing, CDK4/6 inhibitor-based endocrine therapy remains the preferred strategy. However, we increasingly recommend that patients undergo resistance-related genomic testing at the time of metastatic recurrence or disease progression. If resistance-associated genomic alterations are identified, targeted therapies can be prioritized to potentially deliver greater clinical benefit.
In addition, following the inclusion of entinostat in China’s national reimbursement system, the previous “AI + chidamide” recommendation has been revised to “AI + chidamide/entinostat.”
The year 2025 also witnessed the emergence and approval of multiple new CDK4/6 inhibitors. Based on studies such as CULMINATE-2 and BRIGHT-2, along with newly approved indications, several agents—including lerociclib, fulvestrant-based combinations with novel CDK4/6 inhibitors, cumosilib, and pilociclib—have now been incorporated into the unified category of CDK4/6 inhibitor combination therapies.
02
Oncology Frontier: What recent clinical evidence and unmet clinical needs drove these updates? In your opinion, how will these revisions influence real-world clinical practice for HR-positive breast cancer?
Professor Chunfang Hao: Every update incorporated into the guidelines is based on evidence from corresponding Phase III clinical trials, together with regulatory approval status and reimbursement accessibility.
For example, in patients harboring PIK3CA mutations, the INAVO120 study established the efficacy of inavolisib plus palbociclib plus fulvestrant. This regimen is currently considered a preferred option for patients with PIK3CA-mutant disease who are endocrine-resistant to AI therapy and have not previously received CDK4/6 inhibitors.
Meanwhile, capivasertib plus fulvestrant is supported by data from the CAPItello-291 study and addresses the treatment needs of patients who have progressed after both AI therapy and CDK4/6 inhibitors.
As more targeted therapies are incorporated into guideline recommendations, clinical management is increasingly moving toward refined patient stratification and precision-based assessment.
I would summarize the 2026 CSCO BC Guidelines approach to salvage endocrine therapy in HR-positive advanced breast cancer with the following phrase:
“Multi-directional strategies, precision assessment, optimized combinations, and sequential multi-target therapy.”
We now have more therapeutic pathways available for our patients. However, determining the optimal strategy requires clinicians to conduct precise assessments and carefully tailor treatment sequencing according to each patient’s specific clinical and molecular characteristics.
03
Oncology Frontier: From a real-world clinical perspective, what unresolved challenges still remain in the treatment of HR-positive advanced breast cancer? What are your expectations for future guideline updates?
Professor Chunfang Hao: Although treatment options for HR-positive advanced breast cancer continue to expand—with increasing numbers of novel therapies and positive clinical trial results—the unmet clinical needs remain substantial.
Importantly, advances are no longer confined solely to endocrine therapy. ADCs have also demonstrated encouraging efficacy in this field and have already received approved indications. As a result, the 2026 CSCO BC Guidelines now include not only updates in endocrine therapy but also a highly important section focused on HR-positive/HER2-low breast cancer, where ADCs have officially entered the recommended treatment landscape.
However, every new therapeutic strategy also introduces new challenges, including resistance and treatment homogenization.
For example, fulvestrant is now commonly incorporated into combination endocrine regimens. But once patients progress after fulvestrant-based combination therapy, how should subsequent treatment be optimized? At present, we still lack sufficient evidence-based guidance to fully answer this question.
That said, the growing diversity of targeted agents provides us with multiple combination possibilities in clinical practice.
For patients with clearly defined resistance mechanisms, we are increasingly able to select corresponding targeted therapies. For instance, within endocrine therapy, patients harboring alterations in the PIK3CA/AKT1/PTEN pathway now have access to effective targeted treatments.
In addition, ESR1 mutations represent another critically important area of focus.
In 2025, several novel agents targeting ESR1-mutant disease demonstrated positive results, including oral selective estrogen receptor degraders (SERDs) and PROTAC degraders. We hope these new therapies will soon receive regulatory approval or become integrated into routine clinical practice, thereby offering more diverse treatment options for patients with resistant disease.
Looking ahead, we still face several major challenges:
When multiple therapeutic pathways are available, how should clinicians determine the optimal treatment sequence?
Can molecular biomarker testing help guide sequencing strategies for patients with different resistance-associated genomic alterations?
And when patients progress after receiving highly effective targeted therapies or ADCs currently available, what should our next steps be?
I believe the future remains full of possibilities. Emerging targeted therapies will continue providing new solutions to difficult clinical challenges.
At the same time, we hope future clinical research will increasingly focus on patients’ real unmet needs, ultimately helping us build a better therapeutic future for individuals with HR-positive advanced breast cancer.
Professor Chunfang Hao
