Abstract: Objective To investigate the association between tertiary lymphoid structures (TLSs) and clinicopathological parameters， biomarkers， and prognosis in human epidermal growth factor receptor 2 (HER2)⁃low breast cancer among women of reproductive age. Methods Clinical and prognostic data were collected from female patients with HER2⁃low breast cancer， aged 15 to 49 years， treated at Guangxi Medical University Cancer Hospital between January 2019 and December 2022. Whole slide image (WSI) analysis was performed to evaluate the presence and maturity of TLSs in HER2⁃low breast cancer， and their correlation with disease⁃free survival (DFS) was analyzed. Results The analysis included 225 patients， with a median age of 44 years (range: 28-49 years)， and TLSs were detected in 36.0% (81/225) of cases. The presence and maturity of TLSs were significantly associated with tumor histological grade， associated ductal carcinoma in situ (DCIS)， expression of estrogen receptor (ER) ， progesterone receptor (PR) ， Ki⁃67 and molecular subtypes (all P<0.05). Multivariate Cox regression analyses indicated that the presence and maturity of TLSs were independent predictors of decreased DFS (all P<0.05). Conclusions The presence and maturity of TLSs are independently associated with poor prognosis in reproductive⁃aged women diagnosed with HER2⁃low breast cancer. This suggest that TLSs may hold potential as prognostic biomarkers and targets for immunotherapy.

Key words: Breast cancer, Tertiary lymphoid structures, Human epidermal growth factor receptor 2, Reproductive age, Tumor immune microenvironment