Proliferation of breast and endometrial cells is under the control of ovarian steroid hormones (SHs) such as oestrogen and progesterone. They mediate diverse physiological functions via interaction with nuclear-localised steroid hormone receptors (HRs). The SH receptor complex modifies the expression of SH-regulated genes by binding to conserved binding sites in their promoter region or through cross-talk with other transcription factors. In non-malignant tissues, HRs are in balance with other factors regulating proliferation, differentiation and apoptosis. While dysfunction of the regulatory mechanisms is a part of malignant transformation, functional SH receptors can promote growth of SH-responsive tumours. Therefore, anti-hormones that block the interaction of steroid hormones with the SH receptor are useful tools for the treatment of SH-responsive carcinomas. However, a portion of ER-positive breast cancers and most endometrial cancers do not respond to anti-oestrogens and continued treatment results in hormone resistance, mostly without loss of the ER. This review focuses on the mechanisms of action of hormones and anti-hormones in breast and endometrial carcinomas.

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Background: Disruption of the balance between apoptosis and proliferation is considered to be an important factor in the development and progression of tumor. In this study we determined the in vivo cell kinetics along the spectrum of apparently normal epithelium, hyperplasia, preinvasive lesions and invasive carcinoma, in breast tissues affected by fibrocystic changes in which preinvasive and/or invasive lesions developed, as a model of breast carcinogenesis. Materials and method: A total of 32 areas of apparently normal epithelium and 135 ductal proliferative and neoplastic lesions were studied. More than one epithelial lesion per case was analyzed. The apoptotic index (AI) and the proliferative index (PI) were expressed as the percentage of TUNEL (TdT-mediated dUTP-nick end-labelling) and Ki-67 positive cells, respectively. The proliferative/apoptotic index (P/A) was calculated for each case. Results: Statistical analysis demonstrated significant differences among the tissue groups for both indices (P < 0.0001). The Als and PIs were significantly higher in hyperplasia than in apparently normal epithelium (P = 0.04 and P = 0.0005, respectively), in atypical hyperplasia than in hyperplasia (P = 0.01 and P = 0.04, respectively) and in invasive carcinoma than in in situ carcinoma (P = 0.0001 and P < 0.0001, respectively). The two indices were similar in atypical hyperplasia and in in situ carcinoma. The P/A index increased significantly from normal epithelium to hyperplasia (P = 0.01) and from preinvasive lesions to invasive carcinoma (P = 0.04), whereas it was decreased (NS) from hyperplasia to preinvasive lesions. A strong positive correlation between the Als and the Pls was found (r = 0.83; P < 0.0001). Conclusion: These findings suggest accelerating cell turnover along the continuum of breast carcinogenesis. Atypical hyperplasias and in situ carcinomas might be kinetically similar lesions. In the transition from normal epithelium to hyperplasia and from preinvasive lesions to invasive carcinoma, the net growth of epithelial cells results from a growth imbalance in favour of proliferation. In the transition from hyperplasia to preinvasive lesions there is an imbalance in favour of apoptosis.