Editor’s Note: In recent years, immunotherapy, particularly PD-1/PD-L1 inhibitors, has profoundly transformed the treatment paradigm for triple-negative breast cancer (TNBC). The KEYNOTE-522 trial demonstrated that neoadjuvant immunotherapy combined with chemotherapy significantly improves pathologic complete response (pCR) rates, offering new hope for cure in high-risk early-stage patients.
At the CSCO 2025 Annual Meeting, Professor Guohong Song from Peking University Cancer Hospital delivered a comprehensive presentation titled ‘Early-Stage Triple-Negative Breast Cancer: From Chemotherapy to Immunotherapy.’ She reviewed the latest clinical advances and practical strategies in this field.
Following her presentation, Oncology Frontier invited Professor Song to discuss key clinical questions, including selection of patients most likely to benefit from immunotherapy, treatment intensification for non-pCR patients, and management of immune-related adverse events (irAEs) in real-world practice.
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Oncology Frontier: The KEYNOTE-522 study established immunotherapy plus chemotherapy as the standard of care in the neoadjuvant treatment of early-stage TNBC. In clinical practice, how do you identify patients most likely to benefit from immunotherapy? Beyond PD-L1 expression, are there other biomarkers worth considering?
Professor Guohong Song: For early-stage TNBC, adding immunotherapy—particularly pembrolizumab—to standard chemotherapy has been shown to increase the pCR rate. In clinical practice, I generally recommend neoadjuvant chemoimmunotherapy for patients with node-positive disease or tumors larger than 2 cm.
Currently, predictive biomarkers for immunotherapy efficacy in TNBC remain limited. PD-L1 expression is still the primary reference. According to the National Medical Products Administration (NMPA) approval, pembrolizumab is indicated for high-risk early TNBC patients with PD-L1 CPS ≥ 20, confirmed by validated testing methods.
However, data from KEYNOTE-522 showed that both PD-L1–high and PD-L1–low patients benefit from the addition of pembrolizumab, with increased pCR rates across subgroups. While patients with high PD-L1 expression can achieve pCR rates of up to 70%, even those with low expression experience meaningful absolute gains compared with chemotherapy alone.
Therefore, PD-L1 expression is not the sole determinant of immunotherapy benefit; current clinical use is primarily guided by regulatory approval. Other potential biomarkers under investigation include tumor-infiltrating lymphocytes (TILs)—higher TIL levels may predict greater response to immunotherapy. Ongoing studies are also exploring the role of the tumor immune microenvironment and other molecular signatures, though definitive markers have yet to be established.
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Oncology Frontier: For TNBC patients who do not achieve pCR after neoadjuvant immunotherapy plus chemotherapy (non-pCR), what are the current strategies for adjuvant treatment intensification?
Professor Guohong Song: For patients with non-pCR TNBC who have already received immunotherapy in the neoadjuvant setting, the adjuvant phase should continue immunotherapy to complete the prescribed treatment course.
Beyond that, additional adjuvant intensification strategies are available. The CREATE-X study demonstrated that for HER2-negative patients who do not achieve pCR after neoadjuvant chemotherapy, capecitabine can provide significant survival benefit and is therefore an important consideration.
Approximately 10% of TNBC patients carry BRCA mutations. For this subgroup, if residual disease remains after neoadjuvant therapy, olaparib, a PARP inhibitor, can be used as adjuvant therapy to improve invasive disease-free survival (IDFS).
Furthermore, several ongoing clinical trials are exploring next-generation intensification options for non-pCR patients. For instance, antibody-drug conjugates (ADCs) such as sacituzumab govitecan (SG) are being studied in the adjuvant setting, either alone or in combination with immunotherapy or capecitabine. These approaches remain investigational, but we look forward to their results to provide new treatment avenues and improve cure rates for patients with residual disease.
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Oncology Frontier: While immunotherapy provides significant survival benefits, it also introduces the challenge of managing immune-related adverse events (irAEs). How do you and your team monitor, prevent, and manage irAEs during neoadjuvant or adjuvant therapy?
Professor Guohong Song: Indeed, immunotherapy is a double-edged sword—it brings substantial efficacy improvements but also carries the risk of diverse immune-related toxicities. During neoadjuvant or adjuvant therapy, proactive monitoring and early intervention are essential to ensure safety.
Immune-related adverse events can affect multiple organ systems, including thyroid dysfunction, cardiac toxicity, gastrointestinal inflammation, hepatic injury, pneumonitis, and neurologic symptoms. To mitigate these risks, we perform comprehensive laboratory monitoring each treatment cycle—assessing thyroid function, cardiac enzymes, liver and kidney function—and conducting ECG and cardiac imaging regularly.
Patient education is equally important. We counsel patients on recognizing early symptoms such as persistent cough, shortness of breath, or fatigue, and instruct them to report these immediately.
When irAEs occur, management depends on severity. Early recognition and timely corticosteroid or immunosuppressive therapy are critical. Although immune-related toxicities are relatively common and can sometimes be severe, most are manageable with vigilant monitoring, prompt diagnosis, and appropriate intervention.
Our team at Peking University Cancer Hospital takes a multidisciplinary approach to immunotherapy management, ensuring that all patients receiving immune-based treatments are closely followed to maintain both safety and therapeutic efficacy.
Professor Guohong Song
Department of Breast Oncology
Peking University Cancer Hospital
