HER2低表达的乳腺癌（BC）在晚期具有良好的应对新型抗-HER2抗体药物复合物（ADC）的反应。然而，对于接受新辅助治疗（NAT）的HER2低表达乳腺癌的反应、分类变化和预后知之甚少。回顾性研究了自2009年1月至2020年12月期间接受≥ 4个周期NAT和手术的连续浸润性乳腺癌患者。HER2低表达被定义为免疫组化染色（IHC）1+或2+和荧光原位杂交（FISH）阴性。使用Kappa检验分析了HER2及其他生物标志物的一致性率。采用Kaplan-Meier分析和Cox回归评估无复发间隔（RFI）和总生存期（OS）。共纳入了2489名患者，其中1023名（41.1%）患有HER2低表达肿瘤。与HER2-0患者相比，HER2低表达患者的ER阳性率较高（78.5% vs. 63.6%，P < 0.001），乳腺病理完全缓解（pathological complete response，pCR）率相似（20.6% vs. 21.8%，P = 0.617）。在非pCR病例中，39.5％的HER2-0肿瘤变为HER2低表达，14.3％的HER2低表达肿瘤在NAT后变为HER2-0。在ER阳性和ER阴性患者中，HER2低表达状态的一致性率均较低（Kappa = 0.368和0.444）。初级HER2低表达患者的RFI明显优于HER2-0患者（P = 0.014），尤其是在ER阳性子组中（P = 0.016）。此外，与ER阳性子组中RFI相关的是HER2低表达分类变化（调整后P = 0.043）。 与HER2-0患者相比，HER2低表达患者具有较高比例的ER阳性肿瘤和相似的pCR率，这与较好的预后有关，特别是在NAT后的残余病例中。发现初级肿瘤和残余肿瘤之间HER2低表达状态的显著不稳定性，提示在新时代的抗-HER2 ADCs治疗下需要重复检测NAT后的HER2状态。© 2023作者。

HER2-low breast cancers (BC) show a good response to novel anti-HER2 antibody-drug conjugates (ADCs) in advanced setting. Nevertheless, little is known about the response, category change, and prognosis of HER2-low BC receiving neoadjuvant treatment (NAT).Consecutive invasive BC patients who underwent ≥ 4 cycles of NAT and surgery from January 2009 to December 2020 were retrospectively reviewed. HER2-low was defined as IHC 1+ or 2+ and FISH negative. Concordance rates of HER2 and other biomarkers were analyzed by Kappa test. Kaplan-Meier analysis and Cox regression were used to assess the recurrence-free interval (RFI) and overall survival (OS).A total of 2489 patients were included, of whom 1023 (41.1%) had HER2-low tumors. HER2-low patients had a higher ER positivity rate than HER2-0 patients (78.5% vs. 63.6%, P < 0.001), and a similar breast pathological complete response (pCR) rate (20.6% vs. 21.8%, P = 0.617). Among non-pCR cases, 39.5% of HER2-0 tumors changed to HER2-low, and 14.3% of HER2-low tumors changed to HER2-0 after NAT. Low concordance rates of HER2-low status were found in both ER-positive (Kappa = 0.368) and ER-negative (Kappa = 0.444) patients. Primary HER2-low patients had a significantly better RFI than HER2-0 patients (P = 0.014), especially among ER-positive subset (P = 0.016). Moreover, HER2-low category change was associated with RFI in ER-positive subset (adjusted P = 0.043).Compared with HER2-0 patients, HER2-low patients had a high proportion of ER-positive tumor and a similar pCR rate, which were related with better prognosis, especially in residual cases after NAT. A remarkable instability of HER2-low status was found between the primary and residual tumor, indicating re-testing HER2 status after NAT in the new era of anti-HER2 ADCs therapy.© 2023. The Author(s).