Several [10,11,22-25,27,28] but not all [10,26] previous studies have shown that a high tissue level of IGFBP-3 is related to unfavorable prognostic factors of breast cancer, such as large tumor size, elevated S-phase fraction, elevated DNA aneuploidy, and low levels of ER or progesterone receptor. This evidence concerns the gene ESR1 and breast carcinoma.