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Mentally depressed breast cancer (MDBC) patients expressed estrogen receptor (ER) and 16α‑hydroxyestrone (16α‑OHE₁) is directly responsible for causing breast cancer (BC). This study aimed to identify whether depression in breast cancer patients enhanced the production of autoantibodies against 16α‑OHE₁-ER adduct in breast cancer patients. The antibodies in the serum of 65 breast cancer patients (including 35 MDBC) and 40 control subjects were screened by direct binding, inhibition enzyme-linked immunosorbent assay (ELISA), and quantitative precipitin titration. Competition ELISA was also utilized for the estimation of 16α‑OHE₁ in the serum of 30 cancer patients. Autoantibodies from MDBC showed strong recognition to 16α‑OHE₁-ER in comparison to overall breast cancer patients (p < 0.05) and control subjects (p < 0.001). Although breast cancer sera showed high binding to 16α‑OHE₁-ER in …