Editor’s Note The 17th Shanghai Breast Cancer Professional Symposium, held in conjunction with the Annual Meeting of the Breast Cancer Committee of the Shanghai Anti-Cancer Association and the 2026 Breast Cancer Guideline “Red Book” Update Meeting, took place in Shanghai on December 20, 2025. During the meeting, the 2026 Edition of the Essentials of the Breast Cancer Diagnosis and Treatment Guidelines and Specifications—jointly issued by the Chinese Anti-Cancer Association Breast Cancer Committee (CBCS) and the Breast Oncology Group of the Chinese Society of Clinical Oncology (CSOBO)—was officially released (hereinafter referred to as the new Red Book).
Building on the previous edition, the new Red Book has undergone comprehensive and systematic optimization, incorporating the latest and most impactful clinical research findings in the field of breast cancer. Its aim is to provide clinicians with concise, efficient, and scientifically sound guidance for real-world practice. On this occasion, Oncology Frontier invited Professor Jian Zhang from Fudan University Shanghai Cancer Center to discuss key updates in the advanced breast cancer section of the new Red Book, based on his direct involvement in its development, and to share his perspectives on future directions in breast cancer diagnosis and treatment.
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Oncology Frontier: The new Red Book reclassifies HR+/HER2− advanced breast cancer into three categories—endocrine therapy–naïve, secondary endocrine resistance, and primary endocrine resistance—with corresponding adjustments to treatment strategies. Compared with previous classifications, what are the advantages of this updated approach?
Professor Jian Zhang: When revising the classification of patient populations with HR+/HER2− advanced breast cancer, the new Red Book removed the framework based on the Fifth International Consensus Conference for Advanced Breast Cancer (ABC5) and instead adopted definitions from ABC6 and ABC7, as well as recently voted content from ABC8. The core change lies in redefining the previously termed “endocrine-sensitive relapse” population as patients with late-onset or secondary endocrine resistance, resulting in clearer and more clinically meaningful definitions.
Previously, “endocrine-sensitive relapse” generally referred to patients who relapsed one year or more after completing adjuvant endocrine therapy. In reality, however, once disease relapse occurs, it already indicates a degree of resistance to prior endocrine treatment—a conclusion supported by subgroup analyses from multiple clinical studies.
Accordingly, in this update, we followed the ABC6/7 framework and further subdivided patients with secondary endocrine resistance who had received adjuvant endocrine therapy into two groups: those who relapsed after at least two years of adjuvant endocrine therapy but within one year after completing all endocrine treatment, and those who relapsed one year or more after completing adjuvant endocrine therapy. Other definitions of secondary endocrine resistance remain unchanged and continue to include patients who progress after at least six months of first-line endocrine therapy, those who progress after second-line or later endocrine therapy, and patients with known ESR1 mutations. The definition of primary endocrine resistance has also remained unchanged in this update.
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Oncology Frontier: What are the key updates in the treatment of HR+/HER2− advanced breast cancer in the new Red Book?
Professor Jian Zhang: The new Red Book has made several important revisions to the precision treatment section for HR+/HER2− advanced breast cancer. First, it moves the role of precision genomic testing earlier in the treatment algorithm and places stronger emphasis on its importance in guiding clinical decision-making. Correspondingly, additional annotations have been included recommending testing for genes such as ESR1, PIK3CA, AKT, BRCA1/2, and PALB2.
Second, the “treatment strategy” page has been redesigned to reflect a new treatment paradigm. This change is largely driven by the increasing use of CDK4/6 inhibitors in the adjuvant setting. Whether patients previously treated with CDK4/6 inhibitors can undergo CDK4/6 inhibitor rechallenge remains controversial. Based on a comprehensive review of domestic and international literature, the updated Red Book concludes that patients who received CDK4/6 inhibitors as adjuvant therapy and relapsed during treatment or within one year after completion are not suitable candidates for CDK4/6 inhibitor rechallenge. In contrast, patients who relapse more than one year after completing adjuvant therapy may be considered for CDK4/6 inhibitor rechallenge, and treatment strategies are stratified accordingly.
In addition, for patients with PIK3CA mutations who have secondary endocrine resistance or selected cases of primary endocrine resistance, targeted therapy based on the results of the INAVO120 study may be considered. Other precision treatment options include AKT inhibitors for patients with abnormalities in the PI3K–AKT–mTOR pathway (i.e., AKT1 or PTEN mutations), PARP inhibitors for patients with BRCA1/2 mutations, and antibody–drug conjugates (ADCs), such as trastuzumab deruxtecan, for patients with HER2-low expression. Cross-line use of mTOR inhibitors and HDAC inhibitors has also been retained as treatment options.
Overall, the new Red Book clearly reflects the principle of “stratified treatment” in HR+/HER2− advanced breast cancer. Both patient classification and precision treatment strategies have been refined at a fundamental level.
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Oncology Frontier: Which updates in the sections on HER2-positive advanced breast cancer and advanced triple-negative breast cancer (TNBC) stand out most to you in the new Red Book, and how will these changes influence clinical practice?
Professor Jian Zhang: Key updates for HER2-positive advanced breast cancer include the reintroduction of vinorelbine as an optional chemotherapy partner in first-line HER2-targeted therapy, as well as the inclusion of dual HER2 blockade with trastuzumab and pertuzumab (HP) combined with endocrine therapy, with or without CDK4/6 inhibitors, as a first-line treatment option.
In addition, the DESTINY-Breast09 (DB-09) study—which achieved a median progression-free survival (mPFS) of up to 40 months in the first-line setting—has left a strong impression on clinicians. At the recent San Antonio Breast Cancer Symposium (SABCS), quality-of-life results from DB-09 were also reported, showing that patients receiving trastuzumab deruxtecan (T-DXd) plus pertuzumab had quality-of-life outcomes comparable to those in the control group. Based on the DB-09 results, T-DXd has recently received FDA approval for first-line treatment. Although this indication has not yet been approved in China, the new Red Book includes annotations noting that T-DXd plus pertuzumab may be considered for selected patients based on DB-09 findings. We also look forward to the approval of this indication in China in the near future.
In advanced TNBC, the most notable update is undoubtedly the emergence of Trop-2–targeting ADCs. Multiple clinical studies have consistently supported the role of Trop-2 ADCs in first-line treatment, subtly reshaping patient classification. Previously, classification was largely based on PD-L1 expression status, whereas recent trials have increasingly stratified patients based on suitability for immunotherapy.
Because indications for Trop-2 ADCs have not yet been approved, the new Red Book continues to recommend treatment stratification based on PD-L1 expression. For PD-L1–negative patients, sacituzumab govitecan (SG) may be considered based on results from the ASCENT-03 study, although it is listed as an “optional” recommendation due to limitations in evidence level. Trop-2 ADCs combined with immunotherapy, which demonstrated positive results in the ASCENT-04 study, are also included in the annotations.
For patients with BRCA1/2 mutations, treatment with fluzoparib with or without apatinib may be considered based on results from the recently published FABULOUS study. Finally, “stratified treatment” remains a central principle in TNBC management. To this end, the new Red Book specifically highlights individualized treatment approaches based on the “Fudan four-subtype classification.”
The release of the new Red Book will enable clinicians to more precisely stratify patients, perform appropriate molecular testing, and select optimal treatments using the recommended treatment algorithms. Where feasible, it may also support dynamic disease monitoring. At the same time, I hope that more investigator-initiated trials (IITs) led by domestic expert groups will be conducted to explore unanswered questions in breast cancer treatment and further expand therapeutic scenarios and options.
Professor Jian Zhang
Chief Physician of Medical Oncology, Doctoral Supervisor Executive Director, Phase I Clinical Trial Unit Fudan University Shanghai Cancer Center
