Abstract PO1-06-05: Heterogeneity and prognostic characteristics of HER2-low breast cancer: A retrospective analysis of patients with HER2-negative metastatic breast cancer

Abstract Background: It remains uncertain as to whether low levels of HER2 positivity have any prognostic implications in breast cancer patients, whether HER2 levels can be inconsistent between primary tumors and metastatic lesions in individuals with advanced HER2-negative breast cancer, and how such inconsistencies may impact patient prognosis. Methods: A retrospective analysis of advanced breast cancer patients admitted to our hospital from from January 1st, 2010 to January 1st, 2019 was performed, with all patients that underwent at least one metastatic lesion biopsy being screened. The hormone receptor (HR) and HER2 profiles of both primary and metastatic lesions from these patients were confirmed, and HER2-positive patients (HER2 3+ immunohistochemistry IHC results or HER2 2+ IHC results with positive in situ hybridization ISH results) were excluded from further analyses. To examine the prevalence of HER2-low status across primary and metastatic cancers, the current study set out to detect inconsistencies between these two tumor compartments with respect to HER2-low status and to examine the prognostic implications of these findings in patients. Results: The median follow-up duration for this study at the cutoff date (December 31, 2021) was 49.3 (45.8-52.8) months. The current study examined 1,031 participants with HER2 and HR status data from both primary and metastatic tumors. The proportion of HER2-low expression was significantly higher in metastatic lesions than primary tumors (34.7% vs 25.7%), with a corresponding drop in the proportion of HER2-zero metastatic lesions (FIGURE 1). In a multivariate analysis, HER-2 upregulation was linked to HR status, which was established as an independent influencing factor, with such upregulation being most common in HR-positive individuals (P= 0.004). With respect to HER2 status of primary lesions, the medianl survival of patients in the HER2-zero was similar to HER2-low patients, regardless of HR status 44.8 months (95% CI 38.2-54.1) vs 41.5 months (95% CI 35.0-48.0) (P = 0.954)(FIGURE 2A). However, when the HER2 status of metastatic lesions was examined, patients with HER2-low expression had a greater median OS than HER2-zero patients 47.6 months (95% CI 39.6-48.0) vs. 32.2 months (95% CI 24.6-40.0) (P 0.001)(FIGURE 2B). The median OS of patients that exhibited HER2 upregulation (zero→low) was longer than that of patients without such upregulation (zero-zero) (55.8 months (95% CI 45.0-66.6) vs. 32.4 months (95% CI 23.8-41.0)) (P 0.001)(FIGURE 3A). Among HR-positive patients, HER2 upregulation was associated with significantly prolonged OS relative to patients without such upregulation 56.6 months (95% CI 44.6-68.6) vs. 41.7 months (95% CI 31.1-52.3) (P=0.006)(FIGURE 3B), whereas survival outcomes were similar in these two groups in the HR-negative subgroup 44.8 months (95% CI 25.6-64.0) and 25.3 months (95% CI 20.4-30.3) (P=0.103)(FIGURE 3C). However, independent of HR status, the median OS of patients who had HER2 downregulation (low→zero) was similar to those without downregulation (low→low)(FIGURE 3 D, E, F). Conclusion: These results support inconsistencies in HER2-low expression status between primary and metastatic lesions, with low HER2 levels in metastatic tumors being associated with improved survival outcomes. HR-positive patients are more likely to exhibit HER2 upregulation within metastatic lesions and experience corresponding prognostic benefits. Keywords: HER2-low, inconsistency, survival, prognosis, advanced breast cancer Citation Format: Huimin Lv, Min Yan, Mengwei Zhang, Limin Niu, Huiai Zeng, Huihui Sun, Shengnan Zhao, Jing Wang. Heterogeneity and prognostic characteristics of HER2-low breast cancer: A retrospective analysis of patients with HER2-negative metastatic breast cancer 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 PO1-06-05.