Breast Cancer Res Treat. 1998;49 Suppl 1:S27-32; discussion S33-7.  

Clinical importance of intratumoral aromatase.

Miller WR, Mullen P, Telford J, Dixon JM.

Breast Unit, Western General Hospital, Edinburgh, UK.

Evidence to support the contention that estrogen biosynthesis in breast cancers
is of clinical significance has been sought by relating activity to (i) clinical
response to aromatase inhibitors and (ii) tumor concentrations of estrogens.
Significant correlations have been reported between the presence/high levels of
tumor aromatase in vitro and likelihood of response to aminoglutethimide in
patients with advanced breast cancer, but the association is not absolute and it
has been more difficult to demonstrate similar relationships in patients with
earlier stages of cancers treated with other more potent inhibitors. There are
however data to suggest that in vitro measurements of aromatase may not reflect
in situ estrogen synthesis. For example mammary adipose tissue fibroblasts
preincubated with reversible aromatase inhibitors may paradoxically display
elevated in vitro aromatase activity. Similar enhanced in vitro activity may be
observed in breast material taken from patients treated neo-adjuvantly with
aromatase inhibitors such as aminoglutethamide and letrozole. That this is an
artifact of in vitro systems can be demonstrated by performing in situ
assessments of aromatase activity in patients before and after treatment with
aromatase inhibitors. Thus it can be shown that letrozole markedly inhibits in
situ aromatase and reduces tumor levels of estrogens.

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PMID: 9797015 [PubMed - indexed for MEDLINE]