Clinical characteristics and survival outcomes of young women with luminal HER2-low and HER2-ultralow breast cancer.

BACKGROUND

Young women with breast cancer (YWBC) often present with aggressive, hormone receptor-positive tumors. However, the implications of HER2-low and HER2-ultralow expression in this group have not been well characterized despite their potential therapeutic relevance.

METHODS

We conducted a retrospective study of 157 Mexican women aged ≤ 40 years with a prior diagnosis of luminal, HER2-negative breast cancer. HER2 status was reassessed to characterize different levels of HER2 expression within HER2-negative disease, specifically HER2-null, HER2-low, and HER2-ultralow. Clinicopathological features and survival outcomes were compared across groups.

RESULTS

Evaluation of HER2 expression levels identified that 21.0 % of tumors met criteria for HER2-low expression and 18.5 % for HER2-ultralow expression. HER2-low tumors were more prevalent in luminal B disease and were associated with higher Ki-67, lower PR, and increased tumor-infiltrating lymphocytes, while there were no particularities in HER2-null and ultralow tumors. No significant differences were observed in disease-free or overall survival between HER2-null, HER2-low, and HER2-ultralow groups.

CONCLUSIONS

Approximately 40 % of young women with luminal HER2-negative breast cancers have HER2-low or ultralow disease. These findings highlight the importance of accurately assessing HER2 expression in YWBC to identify candidates for emerging HER2-targeted therapies such as trastuzumab deruxtecan.