Role of HER2 in Response to Neoadjuvant Endocrine Therapy in Luminal Breast Cancer

<b>Purpose</b>: Recently, authors have shown increasing interest in the emerging HER2-low subtype in breast cancer. These tumors are currently classified and treated as HER2-negative tumors. Neoadjuvant endocrine therapy (NET) has been used to achieve tumor downstaging and assess treatment response in postmenopausal women with low-grade luminal HER2-negative tumors. This study aimed to determine whether the response to NET was affected by low levels of HER2 expression in luminal tumors. <b>Methods</b>: The study was a single-centered retrospective investigation. Data were gathered from the medical records of patients from 2017 to 2023. All patients had luminal HER2-negative tumors and were treated with NET and subsequent surgery. <b>Results</b>: In total, 175 tumors were analyzed; 24.0% of the tumors were HER2-zero, 48.0% were HER2-low 1+, and 28.0% were HER2-low 2+. No significant differences were found when assessing NET response between the three groups, nor when evaluating tumor features. Response to NET was influenced by estrogen receptor levels, histological subtype and histological grade at diagnosis, Ki67 levels at interim biopsy, and NET duration. No differences were found for progression-free survival (PFS) or overall survival (OS) between HER2 groups. The group with Ki67 ≤ 10% at interim biopsy had longer PFS than the Ki67 > 10% group (<i>p</i> < 0.05). No differences for OS were found between these groups. <b>Conclusions</b>: Response to NET was not influenced by low levels of HER2 expression in luminal tumors when compared to HER2-zero tumors. PFS was longer for patients who had lower Ki67 levels at interim biopsy after NET.