Neoadjuvant HER2 inhibition induces ESR1 DNA methylation alterations resulting in clinically relevant ER expression changes in breast cancers.

In patients with residual disease, gains in ER protein positivity following neoadjuvant therapy were associated with enhanced disease‐free survival (DFS) (Gain HR = 0.37, 95% CI = 0.14‐0.99, P < 0.05) (Figure 1L ) and showed a trend toward an association with overall survival (OS) (Gain HR = 0.40, 95% CI = 0.15‐1.10, P < 0.07, Supplementary Figure S6A ).

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Conversely, ERBB2 promoter hypermethylation at cg15227682 was identified post‐treatment, with promoter hypomethylation observed upon metastasis, though these differences did not reach statistical significance (Figure 1J ).

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