Obesity is a risk factor for breast cancer in older women. A number of
adipose-derived and obesity-related factors have been shown to affect
tumour cell growth. These include adipokines, insulin, IGF-1 and
oestrogens. The majority of obesity-related postmenopausal breast
cancers are oestrogen-dependent. Since the ovaries no longer produce
oestrogens after menopause, and that circulating levels are negligible,
it is evident that it is the oestrogens produced locally within the
breast adipose that are responsible for the increased growth of breast
cancer cells. Aromatase is the enzyme that converts androgens into
oestrogens and its regulation is dependent on the activity of a number
of tissue-specific promoters. Targeting oestrogen biosynthesis in
obesity may be useful for the prevention of breast cancer. Aromatase
inhibitors are efficacious at treating postmenopausal breast cancer and
recent studies suggest that they may also be useful in the prevention
setting. However, these compounds inhibit the catalytic activity of
aromatase and as a consequence lead to a number of undesirable
side-effects, including arthralgia and possible cognitive defects due to
inhibition of aromatase in the bone and brain, respectively. Novel
therapies, such as those employed to treat obesity-associated disease,
including anti-diabetics, may prove successful at inhibiting aromatase
specifically within the breast. This SpringerBrief will explore all of
these issues in depth and the authors are in a unique position to write
about this topic, having extensive experience in the field of aromatase
research.
