267P - The tumour microenvironment influences long-term tamoxifen treatment response in breast cancer patients

Background

The tumour microenvironment (TME) plays a crucial role in the response to treatment of breast cancer patients. Our study investigated whether the immune and stromal cell composition of a tumour can be prognostic for long-term survival.

Methods

The Stockholm Tamoxifen (STO-3) trial, conducted from 1976 to 1990, randomized postmenopausal patients with lymph node–negative breast cancer to receive adjuvant tamoxifen or no endocrine therapy. This study is a subset of 538 patients from STO-3 for which array-based gene expression and more than 20 years of complete patient follow-up data were analysed. TME levels of 18 cell types were assessed by applying the ConsensusTME deconvolution algorithm to the data and dividing the expression levels of each cell type into tertiles. Tertile influence on breast cancer-specific survival (BCSS, cause-specific death from breast cancer) was assessed using univariable Kaplan-Meier and multivariable Cox proportional hazard modelling, adjusting the latter for standard clinical patient and tumour characteristics.

Results

Only fibroblasts, endothelial and mast cells showed statistically significant BCSS differences in univariable analysis of all patients (p < 0.05, log-rank). In multivariable analysis comparing clinical trial arms, low levels of B cells, dendritic cells, NK cells, T-cells (CD4+, CD8+, gamma delta), macrophages M1/M2 and eosinophils were significantly associated with improved BCSS in the tamoxifen-treated patient arm (HRs range from 0.11-0.38 CI 95% [0.04-0.76]). Similarly, low and intermediate levels of cytotoxic cells, macrophages, neutrophils, T reg cells, fibroblasts, monocytes (HRs from 0.24-0.45 CI 95% [0.1-0.99]), or intermediate levels for endothelial cells (HR = 0.18 CI 95% [0.07-0.45]), and low or high levels of mast and plasma cells were associated with improved BCSS in the tamoxifen-treated arm (HRs from 0.20-0.49 CI 95% [0.08-0.92]).

Conclusions

In general, lower levels of TME cells were associated with improved survival in tamoxifen-treated postmenopausal breast cancer patients relative to those who were untreated, suggesting better long-term survival for lower initial TME levels in the tamoxifen-treated patients.

Clinical trial identification

The trial was approved and initiated before the practice of trial registration in Sweden (STOCKHOLM TRIAL, STO-3).

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

This work was supported by the Swedish Research Council [Vetenskapsrådet, grant number 2020-02466 and 2023-03009 to L.S.L.]; the Swedish Cancer Society [Cancerfonden, grant number 222216 to O.S., 232670 to N.P.T., and 222081 and 220552SIA to L.S.L.]; Stockholm Cancer Society [Cancerföreningen iStockholm, grant number 181093 to T.F., 224112 to N.P.T., and 221233 and 201212 to L.S.L.].

Disclosure

All authors have declared no conflicts of interest.