Abstract PO2-01-02: Clinicopathologic features and prognosis of breast cancer with low HER2 expression evaluated by fluorescence in situ hybridization

Abstract Background Although trastuzumab deruxtecan has been found to improve progression-free survival and overall survival of HER2-low breast cancer patients in DESTINY Breast04 trial, the characteristics and prognostic value of low HER2 expression remains to be elucidated. In this study, we retrospectively examined the clinicopathologic characteristics and prognosis of HER2-low expressing breast cancer. Methods A prospective database of 1026 clinical stage I to Ⅲ, HER2 negative breast cancer patients who underwent surgery from September 2012 to October 2022 at Teikyo University Hospital was analyzed. HER2 was evaluated by fluorescence in situ hybridization assay, and HER2-low and HER2-negative was defined as HER2/CEP17 ratio ≧1.0, and 1.0, respectively. The chi-squared test was performed to estimate correlations between HER2-low status and clinicopathological factors. Distant-disease survival (DDFS) was calculated using the Kaplan-Meier curves and log-rank test. Multivariate logistic regression analyses were used to identify the independent prognostic factors. Results Median age, tumor size and ki67 of the entire 1026 patients was 56.0 years (range=23.0-93.0), 2.0 cm (range=0.3-15.0 cm), and 15.0 % (range=0.5-99.0 %), respectively. 155 (15.1 %) patients had lymph node metastasis. 904 (88.1 %) patients revealed hormone receptor positive (estrogen receptor ER positive; 904 patients, progesterone receptor PgR positive; 810 patients). Neoadjuvant and adjuvant chemotherapy was performed in 197 (19.2 %) and 160 (15.6 %) patients, respectively. Among all patients, 904 (88.1 %) patients had HER2-low tumors and 122 (11.9 %) patients had HER2-negative tumors. Positive rate of ER and PgR was significantly higher in HER2-low compared to HER2-negative patients (ER: 804 88.9 % patients vs 100 82.0 % patients; p=0.026 , PgR: 723 80.0 % patients vs 87 71.3 % patients; p=0.028). The median ki67 was significantly lower in HER2-low compared to HER2-negative patients (14.5 % vs 18.5 %, p=0.013). Pathologic complete response rates were not significantly different between HER2-low and HER2-negative patients (16.1 % 27/168 patients vs 17.2 % 5/24 patients, p=0.528). With a median follow-up time of 39.7 months, DDFS was significantly better in HER2-low compared to HER2-negative patients (96.6 % vs 90.7 %, p=0.027). Multivariate logistic regression analyses showed that HER2-low expression was not independently related factors for DDFS. Conclusion These data suggested that HER2-low expression might not have significant association with prognosis despite significant correlation with ki67 and hormone receptor expression. Citation Format: Ayana Sato, Saki Naruse, Yuka Isono, Yuka Maeda, Miki Yamada, Akiko Matsumoto, Tatsuhiko Ikeda, Hiromitsu Jinno. Clinicopathologic features and prognosis of breast cancer with low HER2 expression evaluated by fluorescence in situ hybridization 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 PO2-01-02.