Tumour microenvironment factors may influence cancer progression and response to tamoxifen (Nolvadex) in patients with estrogen receptor-positive and human epidermal growth factor receptor 2 breast cancer

1. In patients with estrogen receptor (ER)+ and human epidermal growth factor receptor 2 (HER2)- breast cancer, certain tumour microenvironments (TMEs) were associated with improved breast cancer progression and treatment response to tamoxifen (Nolvadex).

Evidence Rating Level: 1 (Excellent)

The TME of tumour, immune, and stromal cells varies depending on breast cancer estrogen receptor status. This variability has been shown to influence the survival of breast cancer patients. For example, studies have shown that the presence of CD8+ and activated memory T cells in ER-negative tumours has been associated with increased survival. Thus, it is important to consider TME in addition to ER status. This is a secondary analysis of the Stockholm Tamoxifen Trial 3 (STO-3), which randomized 1780 patients with lymph-node negative breast cancer to two years of adjuvant tamoxifen (40 mg daily) or no adjuvant. 513 patients with available primary tumour formalin-fixed paraffin-embedded material and ER+/HER2- status were included in subset analysis. 274 were treated with tamoxifen (45-54 years: 25 (10.5%); 55-64 years: 118 (49.4%); 65-74 years: 96 (40.1%)) and 239 were untreated (45-54 years: 21 (7.7%); 55-64 years: 139 (50.7%); 65-74 years: 114 (41.6%)). There were no significant differences in tumour size, tumour grade, or progesterone receptor status. The authors determined the normalized enrichment score for 18 TME cell types and summed the standardized scores for all immune cell types to produce one aggregated immune score: “immune abundance”. Low immune abundance was significantly associated with higher ER expression (p<0.001). Furthermore, tamoxifen-treated patients with low immune scores had improved distant recurrence-free interval (DRFI) compared to untreated patients (p<0.001). When considering specific cell types, intermediate endothelial (p<0.001), low fibroblast abundances (p=0.042), and intermediate fibroblast abundances (p=0.009) were also associated with significantly improved DRFI.

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