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Clinical studies with exemestane

  • Robert J. Paridaens
Part of the Milestones in Drug Therapy book series (MDT)

Abstract

Oestrogen is the major stimulus driving the growth of hormone-dependent breast cancer, and most forms of endocrine therapy are directed towards inhibiting, ablating or interfering with oestrogen activity. In young adult women, the ovary is the main source of oestrogen synthesis; after a cascade of biochemical steps, the conversion of androgen precursors (testosterone and androstenedione) into the corresponding oestrogens (oestradiol and oestrone, respectively) ultimately occurs, specifically mediated by the enzyme aromatase. As ovarian function declines with the onset of the menopause, the relative proportion of oestrogens synthesized in extragonadal sites increases, and eventually non-ovarian oestrogens (mainly oestrone) predominate in the circulation. Enzymatic conversion of androgenic precursors (testosterone and androstenedione), secreted by the adrenals, generates oestradiol and oestrone in peripheral tissues. Aromatase, the enzyme responsible for this conversion, is mainly present in adipose tissue, liver, placenta, muscle, skin and brain. Aromatase activity has also been identified in the epithelial and stromal components of the breast. Therefore, local synthesis of oestrogens may contribute to breast cancer growth in postmenopausal women. At the tissue level, complex paracrine and autocrine crosstalk plays an instrumental role in normal breast physiology, but is also crucial for the promotion and development of a cancer. Tumour cells may also be able to produce hormones or growth factors, which either can cause promotion of proliferation or modulate the local environment.

Keywords

Breast Cancer Postmenopausal Woman Clin Oncol Metastatic Breast Cancer Advanced Breast Cancer 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Birkhäuser Verlag/Switzerland 2008

Authors and Affiliations

  • Robert J. Paridaens
    • 1
  1. 1.University Hospital GasthuisbergKatholieke Universiteit LeuvenLeuvenBelgium

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