New approach to SERM resistant breast tumours
Low levels of oestrogen may shrink breast tumours that have developed resistance to tamoxifen and raloxifene, say Chicago researchers.
The scientists say that tamoxifen, a SERM (selective estrogen receptor
modulator), can treat oestrogen receptor positive breast cancers but
often loses efficacy over time and can subsequently stimulate breast
cancer growth.
In a mouse model of tamoxifen-stimulated human breast cancer, they found
that low levels of estradiol caused tumours to regress. The researchers
suggest that this is a result of increased apoptosis (programmed cell
death) through decreased expression of two factors that inhibit this
phenomenon — Her2/neu and NF-kB, and increased expression of a
protein (Fas) which regulates apoptosis.
However, combined treatment with estradiol plus fulvestrant (an anti-oestrogen
approved in the United States for breast cancer treatment) promoted the
growth of tamoxifen-stimulated breast tumours. This suggests that the
use of fulvestrant in patients with a certain level of circulating oestrogen
may stimulate tumour growth (Journal of the National Cancer Institute 2003;95:1597).
The Chicago researchers also express concern that widespread use of raloxifene,
another SERM, will result in some women developing raloxifene-resistant
breast cancer. They developed a model of raloxifene-resistant breast
cancer cells and, again, investigated the effect of low doses of estradiol.
Treatment with estradiol inhibited growth of the resistant cells. Again
apoptosis was increased by lessened NF-kB activity and promoted expression
of the Fas protein (ibid, p1586).
The authors say that these studies “suggest that it is possible
for a patient’s own oestrogen to act as an anticancer agent in
SERM resistant breast cancers”. They add that a novel strategy
of briefly treating patients with oestrogen before reinstituting oestrogen-deprivation
therapy may benefit certain women. |
