Aromatase in the context of breast and endometrial cancer. A review.
Generally, estrogens are considered to be involved in the neoplastic transformation of endometrium. After the menopause these estrogens mainly originate from conversion of adrenal androgens by aromatization in body fat. However, in case of stromal hyperplasia of the ovaries, it cannot be excluded that production of aromatizable androgens by postmenopausal ovaries leads to increased availability of androgen precursors for intratumoral estrogen synthesis in the endometrial tissue as well. The local presence of androgens and the local expression and activity of aromatase is considered important for this steroidogenesis. In this review, we will discuss the available evidence that androgens, produced in hyperplastic ovarian stroma or body fat tissues, play a role in the development of endometrial cancer through conversion into estrogens, a reaction catalyzed in the endometrium by the enzyme aromatase cytochrome P450. As the presence of aromatase appeared to be a pathophysiological factor in the formation of breast cancer, the latter will be evaluated in relation to the development of endometrioid endometrial cancer as well, since both disorders appear partly estrogen dependent. As treatment with aromatase inhibitors appeared feasible in breast cancer, current knowledge of comparable treatment modalities in hormone dependent endometrial cancer will be reviewed.
Jongen
V H W M
VH
Department of Obstetrics, Diaconessenhuis Meppel, Meppel, The Netherlands. Jongvuur@hetnet.nl
Hollema
H
H
Van Der Zee
A G J
AG
Heineman
M J
MJ
D000273:Adipose Tissue / Q000201:enzymology; D000728:Androgens / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001141:Aromatase / Q000502:physiology*; D047072:Aromatase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D001940:Breast / Q000201:enzymology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000209:etiology; D002277:Carcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000209:etiology; D002471:Cell Transformation, Neoplastic; D002986:Clinical Trials as Topic; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000209:etiology; D020847:Estrogen Receptor Modulators / Q000627:therapeutic use; D004967:Estrogens / Q000096:biosynthesis; D005260:Female; D006801:Humans; D006965:Hyperplasia; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000201:enzymology*; D010053:Ovary / Q000201:enzymology / Q000473:pathology; D010166:Palliative Care; D011960:Receptors, Estrogen / Q000378:metabolism; D017154:Stromal Cells / Q000201:enzymology
D000728:Androgens; D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D020847:Estrogen Receptor Modulators; D004967:Estrogens; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D001141:Aromatase