Editor's Note: Recently, the Northern Breast Cancer Salon was successfully held in Qingdao, bringing together leading experts and scholars to discuss the latest advances and clinical hot topics in breast cancer. During the meeting, Professor Jin Yang of the First Affiliated Hospital of Xi'an Jiaotong University delivered a systematic and insightful presentation on controversial issues surrounding immunotherapy for advanced breast cancer. Oncology Frontier interviewed Professor Yang during the meeting to discuss current controversies in immunotherapy, key topics under consideration for the new edition of the Chinese Expert Consensus on the Clinical Application of Immunotherapy for Breast Cancer, and the challenges of translating these recommendations into clinical practice.Oncology Frontier: During this meeting, you gave a presentation on “Controversies in Immunotherapy for Advanced Breast Cancer.” Could you summarize the major controversies currently being discussed in this field?
Professor Jin Yang: In 2024, under the leadership of the CSCO Breast Cancer (BC) Committee, the Chinese Expert Consensus on the Clinical Application of Immunotherapy for Breast Cancer (2024 Edition) was officially published. From 2024 to 2026, however, a series of new evidence-based data on immunotherapy for breast cancer have emerged. Therefore, in my presentation at this meeting, I reviewed the current hot topics and controversies surrounding immunotherapy for advanced breast cancer.
First controversy: What is the optimal partner for immunotherapy?
At the 2025 ASCO Annual Meeting, results from the ASCENT-04 study were presented. The study enrolled patients with previously untreated locally advanced unresectable or metastatic triple-negative breast cancer (mTNBC), all of whom were PD-L1-positive (CPS ≥10) and had completed definitive treatment at least six months earlier. The results showed that sacituzumab govitecan (SG) plus pembrolizumab significantly improved progression-free survival (PFS) compared with chemotherapy plus pembrolizumab (11.2 vs. 7.8 months), reducing the risk of disease progression or death by 35% (HR=0.65, 95% CI: 0.51–0.84; P<0.001).
Data further presented at the 2026 ASCO Annual Meeting showed that although median PFS2 had not yet been reached (NR) in the SG plus pembrolizumab group, it was still significantly better than the 21.0 months observed in the chemotherapy group (HR=0.67). Notably, as many as 81% of patients in the chemotherapy group crossed over to SG after disease progression.
Therefore, even when crossover to SG was permitted in the chemotherapy arm, this did not alter the apparent priority of ADC-based therapy combined with immunotherapy in the first-line setting. Thus, for advanced TNBC, ADC therapy currently appears to be the optimal partner for immunotherapy.
Second controversy: How should first-line treatment be selected for patients with early relapse, particularly those who previously received a PD-1 inhibitor in the neoadjuvant setting?
Approximately 20% of patients enrolled in ASCENT-04 had a disease-free interval (DFI) of only 6–12 months. Subgroup analysis showed a median PFS of 9.9 months in this population (HR=0.62). Therefore, for patients who experience early relapse following neoadjuvant therapy, ADCs appear to have a significant advantage over conventional chemotherapy, particularly among patients with taxane-resistant disease.
A subgroup analysis of KEYNOTE-355 also showed that patients with a DFI of less than 12 months had an HR of 1.0 when treated with conventional chemotherapy plus immunotherapy, indicating limited benefit. Therefore, in this specific population characterized by treatment resistance and early relapse, ADC-based immunotherapy combinations appear to have a clear advantage.
However, both ASCENT-04 and ASCENT-03 included very few patients who had previously received a PD-1 inhibitor with curative intent in the early-stage setting. Consequently, for these patients, whether ADC monotherapy or ADC plus immunotherapy should be preferred in the first-line metastatic setting remains unclear.
Nevertheless, data reported in 2025 from both ASCENT-04 and TROPION-Breast02 demonstrated consistent PFS improvement with Trop-2 ADCs in PD-L1-negative patients, some patients previously treated with PD-1 inhibitors in the early-stage setting, and patients unable to tolerate PD-1 inhibitors. TROPION-Breast02 also demonstrated an OS benefit.
Therefore, ADC monotherapy is currently a reasonable preferred option for these patients. Whether some patients may benefit from immunotherapy rechallenge remains an important question awaiting further evidence.
Third controversy: Can patients with CPS <10 still benefit from immunotherapy?
In China, based on the TORCHLIGHT study led by Professor Zefei Jiang, toripalimab has been approved in combination with nab-paclitaxel for first-line treatment of patients with previously untreated metastatic or recurrent/metastatic TNBC who are PD-L1-positive (CPS ≥1).
The ASCENT-C04 study has now expanded the CPS threshold to patients with CPS ≥1. Meanwhile, the international multicenter MK2870-011/TroFuse-011 study, led by Professor Yongmei Yin, is evaluating sacituzumab tirumotecan plus pembrolizumab versus chemotherapy in patients with PD-L1 CPS <10, with subgroup analyses specifically examining patients with CPS <1 and CPS 1–9.
The results of these studies will further refine our understanding of the appropriate CPS threshold for first-line immunotherapy in advanced TNBC.
The BEGONIA study suggested that the efficacy of ADC plus immunotherapy may not be restricted by PD-L1 expression, although this was an exploratory study. A small phase II study of first-line sacituzumab tirumotecan monotherapy also suggested that efficacy was not strongly associated with PD-L1 expression.
Therefore, for patients with 1≤CPS<10, the clinical benefit of ADC plus immunotherapy still awaits confirmation from additional evidence.
Fourth controversy: Can next-generation immunotherapies overcome local immune tolerance and potentially enable immunotherapy in later lines?
Several clinical studies are currently evaluating PD-L1/CTLA-4 bispecific antibodies, PD-1/VEGF bispecific antibodies, and other approaches. These studies generally do not restrict enrollment according to PD-L1 expression and have prespecified subgroup analyses based on PD-L1 status.
In the future, we hope that these immune-targeted bispecific antibodies will provide a form of “immunotherapy upgrade,” allowing us to overcome the limitations imposed by PD-L1 expression.
At this year’s ASCO meeting, Professor Zhi-Ming Shao’s team reported results from the FUTURE 2.0 study. In patients with HER2-low expression within the BLIS subtype, SHR-A1811 plus bevacizumab was used, while patients with HER2-zero expression received the Trop-2-targeted ADC SHR-A1921 plus bevacizumab. Both approaches improved PFS compared with the respective monotherapy.
This suggests that even in patients with a poor immune microenvironment who would traditionally be considered unsuitable for immunotherapy, ADC plus bevacizumab may achieve meaningful efficacy.
Whether ADC plus bevacizumab can produce substantial advances in later-line treatment remains to be determined. Studies of trispecific antibodies for later-line treatment of advanced TNBC, such as PD-1/CTLA-4/VEGF-directed agents, as well as studies combining HER2-low ADCs with immunotherapy, are currently underway. We look forward to seeing the results.
Fifth controversy: How long should immunotherapy be continued?
In KEYNOTE-355, the median duration of chemotherapy for most patients was six to eight cycles. For patients achieving CR, PR, or SD, continued immunotherapy maintenance can provide significant improvements in PFS and potentially OS. Therefore, immunotherapy maintenance is critical to overall outcomes.
Internationally, some patients receive PARP inhibitors combined with immunotherapy as maintenance after chemotherapy plus immunotherapy. For example, KEYLYNK-009 investigated olaparib plus pembrolizumab as first-line maintenance therapy in metastatic TNBC and showed improvements in median PFS and OS compared with pembrolizumab plus chemotherapy among patients with tumor BRCA mutations.
The domestic COMPLEMENT study, led by Professor Xichun Hu, also evaluated pembrolizumab plus olaparib as maintenance therapy and demonstrated promising efficacy with a favorable safety profile.
Therefore, in clinical practice, maintenance treatment should be individualized according to the patient’s circumstances. For patients who cannot tolerate chemotherapy but have high PD-L1 expression, discontinuing chemotherapy while continuing immunotherapy maintenance is a feasible strategy. In the future, ctDNA clearance may help identify patients suitable for individualized precision maintenance therapy.
Special Populations
In my presentation, I also discussed patients with BRCA mutations, including those with brain metastases.
At this year’s ASCO meeting, biomarker subgroup analyses from ASCENT-04—including analyses of Trop-2, HER2-low expression, and BRCA mutations—showed that among patients with BRCA mutations, SG plus pembrolizumab versus the control arm produced a median PFS of 16.6 versus 12.9 months (HR=0.88). Although the difference was not statistically significant, ADC plus immunotherapy did demonstrate a relatively prolonged PFS.
An ASCO educational session this year recommended immunotherapy plus chemotherapy or ADC-based therapy for patients with PD-L1-positive, BRCA-mutated advanced TNBC.
The domestic ABC study, led by Professor Jian Zhang, demonstrated that adebrelimab plus bevacizumab and platinum-based chemotherapy produced significant intracranial antitumor activity in patients with TNBC and brain metastases, with a CNS objective response rate (CNS-ORR) of 77.1% and a median OS of 21.1 months, with manageable safety. The study was also successfully published in the Journal of Clinical Oncology (JCO).
These findings indicate that immunotherapy-based combination strategies are no longer necessarily off-limits for patients with brain metastases from advanced TNBC and are worthy of further exploration, although radiotherapy remains an important treatment modality.
HR-Positive/HER2-Negative Advanced Breast Cancer
In my presentation, I also reviewed progress in immunotherapy for this population.
Although SG plus pembrolizumab produced an overall negative result in HR-positive patients, PD-L1-positive patients still showed some PFS improvement and a trend toward OS benefit.
I consider patients with low ER expression to be a special population because approximately 40% have PD-L1 CPS ≥10, while among ER-low patients within the BLIS subtype, the proportion is as high as 50%.
For patients with high proliferative activity, high immune infiltration, and low ER expression, their biological behavior may resemble that of TNBC, and immunotherapy-based combinations can therefore be considered.
For HER2-positive breast cancer, however, preliminary results have not demonstrated an improvement in overall outcomes with the addition of immunotherapy to anti-HER2 therapy.
Overall perspective
In my view, the optimal partner for immunotherapy in advanced TNBC is currently an ADC.
For patients with early relapse who are PD-L1-positive and have not previously received a PD-1 inhibitor, ADC plus immunotherapy can be considered. For patients who received a PD-1 inhibitor in the early-stage setting, ADC monotherapy should currently be preferred in the metastatic first-line setting, while the use of combination immunotherapy should await further evidence.
For patients with immune resistance, we hope that bispecific antibodies and other strategies capable of improving the immune microenvironment will provide new approaches to overcoming immune resistance in advanced TNBC.
Immunotherapy maintenance should generally continue until disease progression or unacceptable toxicity, while emphasizing individualized treatment.
For patients with germline BRCA mutations or brain metastases, ADC plus immunotherapy or other immunotherapy-based combinations may be considered. Immunotherapy combined with a PARP inhibitor is also a feasible maintenance strategy.
For patients with brain metastases, adebrelimab combined with bevacizumab and platinum-based chemotherapy represents an important option.
In HR+/HER2-negative advanced breast cancer, patients with low ER expression, high proliferative activity, and PD-L1 positivity may exhibit biological characteristics similar to TNBC and could be considered for immunotherapy-based combinations. For the broader HR+/HER2-negative and HER2-positive populations, immunotherapy combinations are currently not recommended outside clinical trials.
Oncology Frontier: Several experts discussed the “Chinese Expert Consensus on Immunotherapy for Breast Cancer” at this meeting. Could you introduce the key topics discussed? Compared with the existing 2024 edition of the Chinese Expert Consensus on the Clinical Application of Immunotherapy for Breast Cancer, what new areas of focus or potential updates can we expect?
Professor Jin Yang: The 2024 edition of the Chinese Expert Consensus on the Clinical Application of Immunotherapy for Breast Cancer primarily addressed neoadjuvant immunotherapy for early TNBC, treatment of advanced disease, and biomarker testing.
The discussion of the new edition at this meeting focused primarily on several practical issues concerning neoadjuvant immunotherapy.
Specifically, the discussion addressed several clinical controversies:
For patients who respond well to neoadjuvant immunotherapy, should subsequent treatment follow the KEYNOTE-522 regimen with four cycles of EC, or should the TP regimen be extended to six cycles?
How should treatment be adjusted when the response is inadequate?
Should PD-L1 expression be routinely tested in early-stage disease? At present, most experts do not place great emphasis on this in routine clinical practice.
We also discussed whether the chemotherapy backbone must strictly follow the KEYNOTE-522 regimen, whether patients with a lower tumor burden could receive a TP regimen alone, and how TP regimens are actually being implemented across different centers.
At the same time, the meeting explored precision treatment strategies for patients with TNBC who achieve pCR or non-pCR after neoadjuvant therapy.
For patients with non-pCR, the 2026 CSCO Breast Cancer Guidelines have added a dual regimen of PD-1 inhibition plus the PARP inhibitor olaparib, as well as adjuvant escalation with PD-1 inhibition plus capecitabine for patients without germline BRCA mutations.
For patients who achieve pCR, experts were generally consistent in their views regarding further treatment intensification. For patients with BRCA mutations who achieve pCR, most experts believe that PD-1 inhibitor monotherapy is sufficient, even when the patient’s clinical characteristics indicate high risk.
The meeting also conducted voting on issues including whether immunotherapy should be continued in the postoperative adjuvant setting and whether patients with non-pCR following neoadjuvant therapy should continue receiving immunotherapy.
In the advanced setting, given the emergence of new evidence for ADCs, we discussed specific clinical cases to determine which patients with early relapse might be appropriate candidates for ADC plus immunotherapy and which could receive ADC monotherapy.
We also explored new clinical studies, particularly the increasingly diverse treatment options being investigated for PD-L1-positive patients.
These votes and discussions will provide important input for the further revision of the Chinese Expert Consensus on Immunotherapy for Breast Cancer.
Oncology Frontier: From the perspective of clinical practice, what practical changes have the development and dissemination of the “Chinese Expert Consensus on Immunotherapy for Breast Cancer” brought to clinical decision-making, particularly for physicians working in primary-level hospitals? What do you consider the greatest challenge in translating the consensus into routine practice?
Professor Jin Yang: International and domestic guidelines and consensus statements are updated every year, but patients’ clinical conditions do not necessarily conform to guidelines or consensus recommendations.
Therefore, numerous unmet needs remain at critical decision-making points in clinical practice. These include the implementation of PD-L1 testing across different centers, the accessibility of ADCs, and how to identify the patients most likely to benefit from particular treatments. We also encounter complex disease patterns, including early relapse and recurrence after previous exposure to PD-1 inhibitors in the early-stage setting.
Beyond guidelines, expert consensus helps enrich clinical decision-making by providing physicians with additional considerations for individualized treatment.
Every recommendation in the consensus is based strictly on the latest evidence-based medical data, and a recommendation is incorporated into the consensus only when the level of expert agreement reaches more than 80%.
I believe that as new evidence continues to emerge and mature, the Chinese Expert Consensus on Immunotherapy for Breast Cancer will incorporate more new elements and content, further improving the clinical application of immunotherapy in breast cancer.
Professor Jin Yang
First Affiliated Hospital of Xi’an Jiaotong University
