Abstract Background Oestrogen receptor positive (ER+)/HER‐2 negative breast cancer (BC) is considered to be an immunologically cold tumour compared to triple negative breast cancer. Therefore, the tumour microenvironment (TME) of ER+/HER‐2 negative BC is understudied. The aim of this project is to investigate the TME and the immune response during neoadjuvant endocrine therapy (NET) and to correlate this with the treatment response in a real life setting. Methods Expression of immune checkpoint receptors and immune cells was examined immunohistochemically, pre‐ and post‐NET in a cohort of 56 ER+/HER‐2 negative BC patients. They were treated with tamoxifen (n = 16), an aromatase inhibitor (n = 40) or a combination of an aromatase inhibitor with a PI3K inhibitor (n = 11) for a median duration of 6 months (range 1–32 months). Immunohistochemical staining with monoclonal antibodies for PDL‐1, PD‐1, TIM‐3, LAG‐3, CTLA‐4, CD4, CD68 and FOXP3 were performed. All staining procedures were done according to validated protocols, and scoring was done by a pathologist specialized in breast cancer. Positivity was defined as staining >1% on TILs. Response to NET was evaluated according to tumour size change on imaging and Ki‐67 change. Results The median age was 61.02 (37–90) years. Diameter of tumour size decreased with a mean of 8.1 mm (−16 mm to 45 mm) (p
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