Estrogen receptor-α, bcl-2 and c-myc gene expression in fibroadenomas and adjacent normal breast: Association with nodule size, hormonal and reproductive features

Fibroadenomas are the most common benign lump in females. The study of gene alterations and/or deregulation in reproductive years may help explain hormonal physiological processes involved in nodule development and evolution. The objective was to compare ER-α, c-myc, and bcl-2 gene expression in breast fibroadenomas and in normal tissue and evaluate menstrual cycle, parity, and oral contraceptive influences. Fifty-seven premenopausal women (14-49 years) undergoing surgical removal of fibroadenomas were selected. Samples from fibroadenomas and circumjacent normal tissue were obtained for RT-PCR paired analysis. Patients were divided in groups according to menstrual cycle, use of contraceptives and parity. Tissue from 32 patients was adequate for RT-PCR. Paired analysis showed higher expression of ER-α (P = 0.012) and bcl-2 (P = 0.001) in fibroadenomas than in normal breast, while c-myc presented a similar expression (P = 0.655). ER-α was higher in fibroadenomas of patients in follicular phase versus contraceptive users and normal tissue (P = 0.003); bcl-2 was higher in fibroadenomas of patients in luteal phase than in the normal samples from all groups (P = 0.007). c-myc did not differ according to menstrual cycle, but was higher in fibroadenomas >3 cm versus <3 cm (P = 0.015) and in nulliparous women (P = 0.04). A positive correlation between c-myc levels and fibroadenoma diameter was demonstrated (r = 0.536; P = 0.007). Nulliparous mean nodule diameter was superior than parous women (P = 0.008). In conclusion, the expression of ER-α, bcl-2 and c-myc depends on hormonal and reproductive factors, with a possible contribution to lump formation and evolution.