廖宁教授：精准治疗新境，含戈沙妥珠单抗方案为HER2阴性早期乳腺癌注入新动能

导读

2025年欧洲肿瘤内科学会靶向抗癌治疗亚洲大会（ESMO TAT Asia 2025）于7月18～20日在中国香港召开。抗体药物偶联物（ADC）凭借其精准靶向和高效杀伤的特性，成为乳腺癌领域的焦点药物，其中TROP-2是ADC备受关注的治疗靶点。戈沙妥珠单抗（SG）是全球首个获批的TROP-2 ADC，在HER2阴性晚期乳腺癌中表现优异，并不断探索，将治疗脚步前移至早期新辅助阶段。在本次ESMO TAT Asia大会上，广东省人民医院廖宁教授报告了SG在真实世界HER2阴性早期乳腺癌人群中新辅助治疗数据，引发广泛讨论。据此，本期【医脉有声】特邀广东省人民医院廖宁教授立足HER2阴性乳腺癌治疗现状，分享SG在HER2阴性乳腺癌的前沿进展，为临床诊疗提供更多参考。

Q1：当前HER2阴性早期乳腺癌存在哪些未竟之需？其治疗现状如何？

廖宁教授

HER2阴性乳腺癌包括TNBC和HR+/HER2-乳腺癌，对于HER2阴性早期乳腺癌而言，实现肿瘤降期、重获手术/保乳/保腋窝等机会至关重要1。新辅助治疗是实现这些治疗目的的重要途径，尽管不同亚型患者对新辅助治疗的响应不同，但患者均能从中受益，获得更多生存机会2-3。目前KEYNOTE-522研究已初步证实，免疫联合化疗新辅助治疗早期TNBC可改善患者预后4。

Q2：近年来，抗体药物偶联物（ADC）等抗肿瘤新药的涌现，为HER2阴性乳腺癌带来了怎样的获益？有哪些值得关注的治疗进展？

廖宁教授

ADC的面世给乳腺癌治疗带来了更多选择，戈沙妥珠单抗（SG）是全球首个获批的TROP-2 ADC，在mTNBC二线治疗及HR+/HER2-晚期乳腺癌内分泌耐药后治疗中显示出卓越疗效，并将探索脚步前移至晚期一线及早期新辅助阶段。在一线治疗阶段，ASCENT-03研究表明，SG单药一线治疗晚期TNBC可显著改善患者的无进展生存期（PFS）5；在新辅助治疗阶段，NeoSTAR研究的A1队列结果显示，SG单药4个周期新辅助治疗TNBC的病理完全缓解（pCR）率为30%，未见新的安全性信号6。

虽然 ADC单一疗法在HER2阴性乳腺癌治疗中显示出显著的生存获益，但临床前进的脚步并未停止，临床医生期待通过探索ADC联合其他治疗方案进一步优化治疗策略，特别是ADC联合免疫治疗，已成为乳腺癌领域的热门探索方向。从作用机制层面来看，ADC能够通过诱导免疫原性细胞死亡、树突状细胞激活以及记忆T细胞激活等，与免疫细胞相互作用，诱发长期的抗肿瘤免疫，产生潜在的协同效应7。

在临床试验中，ADC与免疫治疗联合用于HER2阴性乳腺癌抗肿瘤治疗的协同效应也得到了验证。ASCENT-04研究证实，SG联合帕博利珠单抗一线治疗mTNBC患者具有显著疗效，中位PFS达11.2个月，不良反应可控8；在HER2阴性早期乳腺癌领域，NeoSTAR研究的A2队列结果显示，SG联合帕博利珠单抗新辅助治疗早期TNBC，32%的患者达到pCR，并且未发现新的安全性信号，验证了联合方案的治疗潜力和一致的安全性9。目前NeoSTAR研究正在对HR+乳腺癌（队列B）进行SG联合免疫新辅助治疗的探索，数据值得期待，有望为乳腺癌新辅助治疗“豁免化疗”策略提供新的方向。

Q3：多项研究表明，以SG为基础的新辅助治疗方案（SG单药或联合治疗）可改善早期患者预后，该方案在临床实践中表现如何？

廖宁教授

既往临床试验已表明，SG单药或联合治疗方案作为早期乳腺癌患者的新辅助治疗具有一定疗效与可控的安全性，其在真实世界中的临床数据进一步揭示了这一组合的临床价值。此次在香港举办的2025年ESMO TAT ASIA大会上，我们中心报告了一项真实世界研究证据，证实了以SG为基础的新辅助治疗在HER2阴性早期乳腺癌患者中具有良好的抗肿瘤疗效和可控的安全性10。

本研究共纳入21例真实世界早期HER2阴性乳腺癌患者（11例HR+，10例TNBC），治疗方案探索性尝试了包含SG单药、联合免疫或内分泌治疗等以SG为基础的新辅助方案治疗。52.3% 的患者接受2-4周期的含戈沙妥珠单抗治疗，47.7%的患者接受了5-9周期的含戈沙妥珠单抗治疗，52.4%（11/21）患者接受联合免疫检查点抑制剂治疗。

疗效分析显示，TNBC中有6例（6/10）患者获得了病理完全缓解，pCR率为60%，其中有4例患者携带与DNA损伤修复相关基因突变，pCR率为75%（图1）；在激素受体阳性乳腺癌患者中，共有1例（1/11）获得了病理完全缓解，pCR率为9.1%。包含戈沙妥珠单抗治疗方案在全体人群中的影像学客观有效率为76.1%（16/21），在激素受体阳性患者的影像学客观有效率为81.8%（9/11）（图2），其中未获得病理完全缓解的患者90%（9/10）术后Ki-67相较于术前下降，有8例患者的Ki-67降低至20%以内（图3）。

图1. TNBC患者所有疾病分期的pCR率10

图2. 新辅助治疗后的pCR和ORR10

图3. 激素受体阳性患者手术前后Ki-67的变化10

安全性分析显示，SG单药和联合治疗均未观察到新的安全性信号，不良反应多为1-2级，常见不良反应为恶心（57.1%）、脱发（38.1%）和中性粒细胞减少（33.3%），有3例患者发生3级以上的中性粒细胞减少（14.3%，3/21），1例患者因免疫治疗相关内分泌毒性停用免疫治疗，整体安全性可控。

表1. 新辅助治疗期间的不良事件10

总体而言，以SG为代表的TROP-2 ADC已从HER2阴性乳腺癌的晚期阶段逐步扩展到早线甚至是早期新辅助治疗，以SG为基础的治疗方案也正在改写乳腺癌的临床实践。同时，SG在真实世界中的探索性临床数据，初步证实了以SG为基础的新辅助治疗方案在HER2阴性患者中的可行性与耐受性。展望未来，随着临床探索的不断深入，SG与免疫治疗、内分泌治疗等的“豁免化疗”组合，或将成为HER2阴性乳腺癌个体化新辅助治疗的核心拼图，有望持续改写乳腺癌全程临床实践，为患者带来更多获益！

Introduction

The European Society for Medical Oncology Targeted AntiCancer Therapies Asia Congress 2025(ESMO TAT Asia 2025) was held in Hong Kong, China, from July 18 to 20. Antibody-drug conjugates (ADCs) have become focal point in breast cancer treatment due to their precise targeting and high efficacy, TROP-2 is a highly sought-after therapeutic target for ADCs. Sacituzumab govitecan (SG) is the first TROP-2 ADC approved globally, demonstrating excellent efficacy in HER2-negative advanced breast cancer, and continuously exploring the extension of treatment to the early neoadjuvant stage. At ESMO TAT Asia 2025, Professor Liao Ning from Guangdong Provincial People's Hospital presented real-world data on neoadjuvant therapy with SG in HER2-negative early-stage breast cancer patients, sparking widespread discussion. Medlive has invitedProfessor Liao Ning from Guangdong Provincial People's Hospitalto share the latest advancements in SG for HER2-negative breast cancer, providing additional insights for clinical diagnosis and treatment.

Q1：What are the current unmet needs in HER2-negative early-stage breast cancer? what is the current treatment landscape?

Professor Liao Ning

HER2-negative breast cancer includes triple negative breast cancer(TNBC) and hormone receptor positive/human epidermal growth factor-2 negative(HR+/HER2-) breast cancer1. For HER2-negative early-stage breast cancer,it is crucial to achieve tumor downstaging and regain the opportunity for surgery, breast-conserving surgery, or axillary-conserving surgery.Neoadjuvant therapy is an important strategy to achieve these therapeutic goals, although response rates to neoadjuvant therapy vary across molecular subtypes, patients can derive survival benefits from this approach2-3. The KEYNOTE-522 trial has preliminarily demonstrated that combining immunotherapy with chemotherapy in the neoadjuvant setting improves outcomes in early-stage TNBC4.

Q2：In recent years, the emergence of antibody-drug conjugates (ADCs) and other novel antineoplastic agents has brought new benefits to HER2-negative breast cancer. What are noteworthy therapeutic advances?

Professor Liao Ning

The introduction of ADCs has significantly expanded the treatment options for breast cancer. Sacituzumab govitecan (SG), the first approved TROP-2-directed ADC in the world, has demonstrated excellent efficacy in second-line metastatic TNBC and in HR+/HER2- advanced disease after endocrine resistance.Moreover, SG is being advanced into earlier lines of therapy, including first-line metastatic and even neoadjuvant early-stage settings.In the first-line metastatic setting, the ASCENT-03 trial showed that SG monotherapy as first-line therapy significantly prolonged progression-free survival (PFS) in metastatic TNBC5.In the neoadjuvant setting,the NeoSTAR trial (cohort A1) reported a pCR rate of 30 percent after four cycles of SG monotherapy in TNBC, with no new safety signals6.

Although ADC monotherapy has shown significant survival benefit in the treatment of HER2-negative breast cancer,clinical development is moving forward. Clinicians are eager to further optimize treatment strategies by exploring ADC in combination with other treatment regimens, particularly ADC in combination with immunotherapy, which has become a hot area of exploration in the field of breast cancer. Mechanistically,ADCs can induce immunogenic cell death, activate dendritic cells, generate of memory T cells, interacting with immune cells and generating potential synergistic effects7.

The synergistic effect of ADC in combination with immunotherapy for antitumor treatment of HER2-negative breast cancer has also been demonstrated in clinical trials. The ASCENT-04 trial demonstrated that SG combined with pembrolizumab as first-line therapy for metastatic TNBC,achieved a median PFS of 11.2 months, with manageable toxicities8. In early-stage HER2-negative disease,NeoSTAR trial cohort A2 showed that neoadjuvant SG combined with pembrolizumab achieved pCR rate in 32 percent of early-stage TNBC patients without new safety concerns, validating the therapeutic potential and consistent safety of the combination regimen9.The NeoSTAR trial is currently exploring SG combined with immunotherapy neoadjuvant therapy in HR+ breast cancer (Cohort B), and the data are promising, and are expected to provide a new direction for the "chemo-free" strategy of breast cancer neoadjuvant therapy.

Q3：Multiple studies suggest that SG-based neoadjuvant regimens (SG alone or in combination) improve outcomes in early-stage patients. How does this regimen perform in real-world clinical practice?

Professor Liao Ning

Previous clinical trials have demonstrated the efficacy and manageable safety of SG monotherapy or combination regimens as neoadjuvant therapy for early-stage breast cancer patients. Real-world data further corroborate these findings. At the 2025 ESMO TAT ASIA Congress in Hong Kong, our center reported the real-world data, which confirmed that SG-based neoadjuvant therapy has favorable anti-tumor efficacy and manageable safety in patients with HER2-negative early-stage breast cancer10.

A total of 21 patients with early-stage HER2-negative breast cancer (11 HR+, 10 TNBC) in real-world were enrolled in this study, andthe treatment regimen explored SG-based neoadjuvant therapy containing SG monotherapy, combined immunotherapy or endocrine therapy. 52.3 percent of patients received 2-4 cycles of SG-based therapy, and 47.7 percent of patients received 5-9 cycles of SG-based therapy, and SG combined with immunotherapy was administered to 52.4 percent of patients.

Efficacy analysis showed that six patients (6/10) withTNBC achieved pathological complete response with a pCR rate of 60 percent, including four patients harboring mutations in genes associated with DNA damage repair, with a pCR rate of 75.0 percent(Figure 1), and one patient (1/11) with hormone receptor positive breast cancer achieved a pathological complete response with a pCR rate of 9.1 percent.The radiological overall objective response rate of the treatment regimen SG-based was 76.1 percent (16/21) in the overall population, and 81.8 percent (9/11) in hormone receptor-positive patients(Figure 2),with 90 percent (9/10) of patients who did not achieve a pathological complete response, Ki-67 decreased after surgery compared to before surgery, with 8 patients showing a reduction in Ki-67 to less than 20 percent(Figure 3).

Figure 1. Pathological complete response rate of all stages of disease in the triple-negative breast cancer group10

Figure 2. PCR rate and ORR of disease after neoadjuvant treatment with Sacituzumab govitecan10

Figure 3. Preoperative and postoperative changes in Ki-67 in the HR+ group10

Safety analysis showed that no new safety signals were observed with SG monotherapy and combination therapy, and most adverse events were grade 1-2, with common adverse events including nausea (57.1%), alopecia (38.1%), and neutropenia (33.3%), and grade 3 or higher neutropenia occurring in 3 patients (14.3%, 3/21), and 1 patient discontinued immunotherapy due to immunotherapy-related endocrine toxicity, Overall, the safety profile was manageable.

Table 1. Adverse events during neoadjuvant therapy10

In conclusion, TROP-2-directed ADC represented by SG has been gradually expanded from the advanced stage of HER2-negative breast cancer to front-line even early-stage as neoadjuvant therapy, and SG-based treatment regimens are rewriting the clinical practice of breast cancer. Meanwhile, exploratory clinical data in the real world have initially confirmed the feasibility and tolerability of SG-based neoadjuvant regimens in HER2-negative patients.In the future, with the deepening of clinical exploration,the combination of SG with immunotherapy or endocrine therapy and other “chemo-free” treatments,may become the key component of individualized neoadjuvant therapy for HER2-negative breast cancer,which is expected to rewrite the whole clinical practice of breast cancer and bring more benefits to patients!

专家简介

廖宁 教授

• 医学博士，教授，博士生导师

• 广东省人民医院外科乳腺科行政主任

• 广东省医师协会乳腺专科医师分会主任委员

• 中国抗癌协会乳腺癌专业委员会（CBCS）常务委员

• 国际肿瘤学预防和治疗学会(ISOPT)公共教育主任

• 美国肿瘤外科学会（SSO）国际理事会理事

• 国际前哨淋巴结学会（ISNS）国际理事会理事

• 美国癌症研究协会（AACR）中国区顾问

• 国家卫生健康委员会医政司《乳腺癌诊疗规范》编写组成员

• 国家卫生健康委员会合理用药专家委员会抗肿瘤药物专业组成员

• 美国国家综合癌症网络（NCCN）肿瘤临床实践指南乳腺癌（中国版专家组成员）

• 圣加仑早期乳腺癌治疗国际共识指南（中文版）专家组成员

简介

任永琪 医生

• 广东省人民医院外科乳腺科

• 在读博士

• 《Evaluation of the efficacy and safety of a neoadjuvant therapy based on Sacituzumab Govitecan for HER2-negative breast cancer: a retrospective study in the real world.》第一作者

参考文献：

1. 《中国乳腺癌新辅助治疗专家共识（2022年版）》专家组 . 中国乳腺癌新辅助治疗专家共识（2022年版）［J］. 中国癌症杂志, 2022, 32 (1): 80-89.

2. 吴淞，江泽飞．基于新辅助治疗效果的乳腺癌辅助治疗策略[J]．中华外科杂志，2024，62（2）：104-109．

3. Bischoff H, Espié M, Petit T. Neoadjuvant Therapy: Current Landscape and Future Horizons for ER-Positive/HER2-Negative and Triple-Negative Early Breast Cancer. Curr Treat Options Oncol. 2024;25(9):1210-1224.

4. Schmid P, Cortes J, Dent R, et al. Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer. N Engl J Med. 2022;386(6):556-567.

5. https://www.businesswire.com/news/home/20250523076969/en/ASCENT-03-Trodelvy-Demonstrates-Highly-Statistically-Significant-Clinically-Meaningful-Improvement-in-Progression-Free-Survival-in-Patients-With-First-line-Metastatic-Triple-Negative-Breast-Cancer-Who-Are-Not-Candidates-for-Checkpoint-Inhibitors

6. Spring LM, Tolaney SM, Fell G, et al. Response-guided neoadjuvant sacituzumab govitecan for localized triple-negative breast cancer: results from the NeoSTAR trial. Ann Oncol. 2023 Dec 12:S0923-7534(23)05107-4.

7. Lv Y, Cui X, Li T, et al. Mechanism of action and future perspectives of ADCs in combination with immune checkpoint inhibitors for solid tumors. Clin Exp Med. 2025;25(1):139. Published 2025 May 4.

8. Sara M. Tolaney, et al. Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in previously untreated PD-L1–positive advanced triple-negative breast cancer (TNBC): Primary results from the randomized phase 3 ASCENT-04/KEYNOTE-D19 study. 2025 ASCO LBA 109.

9. Rachel Abelman, et al. A phase 2 study of response-guided neoadjuvant sacituzumab govitecan and pembrolizumab (SG/P) in patients with early-stage triple-negative breast cancer: Results from the NeoSTAR trial.2025 ASCO 511.

10. Yongqi Ren, et al.Evaluation of the efficacy and safety of a neoadjuvant therapy based on Sacituzumab Govitecan for HER2-negative breast cancer: a retrospective study in the real world.2025 ESMO TAT ASIA Poster #15eP.

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审校：Elan

排版：Sophia

执行：Uni

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