149P HER2-low status and response to neoadjuvant chemotherapy in early breast cancer

Some recent evidence has suggested that HER2-low breast cancers (BC) are distinct entities. The prognostic impact of low expression of HER-2 are not yet well defined, and inconsistent results were reported. This study aims to evaluate the impact of low HER-2 status on the response to neoadjuvant chemotherapy (NACT). We retrospectively analyzed HER2-negative BC patients treated with NACT from 2017 to 2022 in a single academic center. HER-2 low status was defined by IHC +1 or +2 ISH non-amplified, and HER2-zero was defined by IHC 0. The primary objective was to compare pathological complete response (pCR) rates between HER2-low and HER2-zero populations. 101 patients were identified. 70 (69.3%) patients had hormone receptor (HR) positivity, and 31 (30.7%) patients had TNBC. Overall 70 (69.3%) patients were HER2-zero and 31 (30.7%) patients were HER2-low. Among HR-positive patients, 25 (35.7%) were HER2-low, while only 6 (19.3%) patients were her2 low in TNBC group,There were no significant differences in median age, Ki67 score, histology, menopausal status, histologic grade, or T stage between the HER2-zero and HER2-low groups. There were also ER level differences between HER2-zero and HER2-low tumors; the median ER level was 75% for HER2-zero tumors and 90% for HER2-low tumors (p = 0.028). Overall, pCR was achieved in 24 (23.7%) patients. Among HER2-zero patients 21 (30%) had pCR while 3 (9.7%) patients had pCR in the HER2-low group (p=0.027). In the HR-positive subtype, there were still statistically significant pCR differences between the two groups. 15 patients had pCR in the HR-positive group; among these, 13 (87%) patients had HER2-zero tumors, while 2 (13%) of them had HER2-low tumors (p = 0.041). In the TNBC subtype, 9 patients had pCR; 8 (89%) of them had HER2 zero and 1 (11%) had HER2-low tumors, but there was no statistical significance in the TNBC group (p = 0.642). Our results show that HER2-low tumors have a different response to NACT. Both in the overall group and the HR-positive subgroup, HER2-low tumors had significantly lower pCR rates. Because of the cross-talk between HR signaling and HER2 signaling, low HER2 expression may be responsible for treatment resistance in HR-positive BC.