SAN FRANCISCOFive years of tamoxifen (Nolvadex) is standard
treatment for many women with estrogen-receptor (ER)-sensitive breast cancer,
but the question of what to do after that is unresolved. Raloxifene (Evista)
has been considered by some researchers as a possible next treatment, but
preclinical data suggest this will not be a successful strategy. Ruth M. O’Regan,
MD, of Northwestern University Robert H. Lurie Comprehensive Cancer Center,
presented the data at the 37th Annual Meeting of the American Society of
Clinical Oncology (ASCO abstract 95).
Neither tamoxifen nor raloxifene blocked estrogen-stimulated tumor growth in
mouse models. "Tamoxifen and raloxifene are cross-resistant in models of
tamoxifen-resistant breast and endometrial cancer. We should not assume that
raloxifene will be effective after 5 years of tamoxifen," Dr. O’Regan
Furthermore, she said, there is evidence from this study that raloxifene,
like tamoxifen, can stimulate the growth of some breast or endometrial cancers.
Raloxifene attracted the interest of breast cancer researchers because it is
an antiestrogen but, unlike tamoxifen, does not cause endometrial thickening.
"We now know that tamoxifen increases the risk of endometrial cancer by
threefold to fourfold in women," Dr. O’Regan said.
In this study, athymic mice were bitransplanted with breast cancer tumors on
one side and endometrial tumors on the other, and treated with tamoxifen or
raloxifene, with and without postmenopausal levels of estrogen.
The study used models of tamoxifen-sensitive cancers and of both short-term
and long-term tamoxifen-resistant cancers, simulating the situation of women
with breast cancer who develop progressive disease while on tamoxifen.
Tamoxifen and raloxifene had similar effects in all the models tested. In
tamoxifen-sensitive tumors, neither drug stimulated growth of breast or
endometrial cancers. In the short-term tamoxifen-resistant breast cancer
model, both raloxifene and tamoxifen stimulated tumor growth. In the long-term
tamoxifen-resistant models, both drugs stimulated growth of tamoxifen-exposed
endometrial and breast cancers.