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FOXP3 genetic polymorphisms have been associated with cancer development and prognosis. In this context, the present study aimed to evaluate the g.10403A>G (rs2232365) polymorphisms and g.8048A>C (rs3761548), in aggressive breast cancer (BC) subtypes, including, Luminal B HER2+ (LB), HER2-enriched (HER2+), and triple-negative (TN). Polymerase chain reaction followed by enzymatic restriction was performed to genotyping 117 BC samples and 300 controls. A significant association of AA genotype (g.10403A>G) in relation to BC susceptibility (OR = 1.93; 95% CI = 1.01–3.66; p=0.046) was observed. The GG (g.10403A>G) genotype was correlated with higher proliferation index (Ki-67) in HER2+ subtype (τ = 0.47; p=0.019) and advanced TNM staging in TN (τ = 0.23; p=0.032). A correlation of AA genotype (g.8048A>C) with higher Ki-67 (τ = −0.47; p=0.018) and lower histological grade (τ = 0.39; p=0.026) in HER2+ was also found. GA haplotype was correlated with lower histological grade (τ = −0.15; p=0.009) and higher Ki-67 (τ = 0.43; p=0.036) in HER2+ and advanced staging in TN (τ = 0.29; p=0.044). On the other hand, AC haplotype was correlated with lower Ki-67 (τ = −0.54; p=0.005) and staging (τ = −0.29; p=0.027) in HER2+ and TN respectively. Results showed that FOXP3 influence regarding clinical outcome depends greatly on the BC subtype and indicated this transcription factor as a promising marker in aggressive BC subtypes.

FOXP3 Allelic Variants and Haplotype Structures Are Associated with Aggressive Breast Cancer Subtypes