Abstract PO5-02-10: Favorable effect of HER2-low expression on prognosis for breast cancers after neoadjuvant chemotherapy

Abstract Background The clinicopathological characteristics, pathological complete response and survival outcomes of HER2-low, HER2-zero and HER2-positive breast cancers are yet to be elucidated in Chinese patients especially those administered neoadjuvant chemotherapy. Methods We retrospectively identified 259 patients with different HER2 statuses (zero, low and positive) who underwent surgery as planned after neoadjuvant chemotherapy from a prospectively maintained institutional cohort database in Renji Hospital, School of Medicine, Shanghai Jiao Tong University between 2014 and 2019. Overall survival (OS) denoted the time from surgery to death, irrespective of cause. Locoregional relapse-free survival (LRFS) was estimated from surgery to first occurrence of locoregional, ipsilateral relapse, or death, irrespective of cause. We defined pathologic complete response (pCR) as ypT0 ypN0 (absence of cancer in the breast and axillary nodes). The definition of ypT0/is ypN0 (absence of invasive cancer in the breast and axillary nodes, irrespective of ductal carcinoma in situ) was evaluated as an additional endpoint. Results A total of 89 (34.36%), 66 (25.48%) and 104 (40.16%) HER2-low, HER2-zero and HER2-positive breast cancers were enrolled in this analysis, respectively. The median follow-up interval was 5.74 years. Hormone receptor(HR) expression was numerically more common in HER2-low breast cancers than the other two subgroups (83.15% in HER2-low vs 72.73% in HER2-zero vs 77.88% in HER2-positive, P 0.05). The level of Ki-67 index was significantly lower in the HER2-low tumors than that of HER2-zero tumors (P=0.023). HER2-positive tumors had the highest proportion of histological grade III (P=0.005). The HER2-low breast cancers showed significantly better OS (P=0.0056) and LRFS (P=0.002) than HER2-zero counterparts. Subgroup analysis revealed the similar benefit in LRFS (P=0.018) rather than OS (P=0.055) for patients with HR positive/HER2-negative tumors. When the HER2-positive tumors was combined together for comparison, the OS (P=0.016) and LRFS (P=0.0062) also significantly differed among patients with HER2-low, HER2-zero, and HER2-positive tumors. Additionally, the HR negative patients had analogous OS outcome to the entire population according to different HER2 status (P=0.041). Multivariable Cox-regression analysis and external validation in the TCGA database as well as Kaplan-Meier plotter database supported that HER2-low tumors and HER2-positive tumors treated with HER2-directed therapy may have similar survival outcomes, while HER2-zero peers may have the worst outcome compared with the above two groups. There were no remarkable differences in pCR rates between HER2-low and HER2-zero tumors after neoadjuvant chemotherapy (ypT0ypN0 and ypT0/isypN0, P=0.452 and P=0.777, respectively). HER2-positive tumors had a significantly higher pCR rate, especially compared to HER2-low tumors in the entire population (both P 0.001) as well as in the HR positive subgroup (both P 0.0001). The pCR status affected survival outcomes for breast cancers with different HER2 status. As for those without pCR, the HER2-low subgroup showed a remarkably better performance compared with HER2-zero patients in terms of OS (P=0.018) and LRFS (P=0.005), while little difference was found for patients who achieved pCR. Conclusion Our study demonstrated that HER2-low breast cancer may be a different entity from HER2-zero or HER2-positive tumors, which provide illuminating evidence in view of patients receiving neoadjuvant treatment. Citation Format: Yingying Zhao, Wenjin Yin, Xinru Chen, Jingsong Lu. Favorable effect of HER2-low expression on prognosis for breast cancers after neoadjuvant chemotherapy abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-02-10.