A review.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 Jan. 2009 to Dec. 2020 were retrospectively reviewed.HER2-low was defined as IHC 1+ or 2+ and FISH neg.Concordance rates of HER2 and other biomarkers were analyzed by Kappa test.Kaplan-Meier anal. 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 pathol. 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-pos. (Kappa = 0.368) and ER-neg. (Kappa = 0.444) patients.Primary HER2-low patients had a significantly better RFI than HER2-0 patients (P = 0.014), especially among ER-pos. subset (P = 0.016).Moreover, HER2-low category change was associated with RFI in ER-pos. subset (adjusted P = 0.043).Compared with HER2-0 patients, HER2-low patients had a high proportion of ER-pos. 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.