Raloxifene (RAL), a selective estrogen receptor modulator (SERM), is approved for the prevention of osteoporosis in postmenopausal women, and is being compared with tamoxifen (TAM) in the STAR prevention trial. TAM, another SERM, is well-documented to stimulate the growth of breast cancer in vivo , and withdrawal responses to TAM have been noted clinically. We have developed a RAL-stimulated breast cancer model, by exposing MCF7 tumors to RAL in vivo . Methods: RAL-stimulated breast tumors were developed by implanting athymic, ovariectomized mice with hormone-responsive MCF7 breast tumors, and treating the mice with RAL 1.5mg daily for 24 weeks. These RAL-stimulated breast (MCF7RAL) tumors were implanted into athymic mice, and the mice were treated with postmenopausal estrogen (E2), TAM (1.5mg/daily PO), RAL (1.5mg/daily PO), or the pure antiestrogen, ICI 182,780 (ICI) (5mg SC every 3 days), with and without E2, or no treatment. Estrogen receptor (ER) α expression was measured by immunohistochemistry. Results: Postmenopausal E2 stimulated growth of the MCF7RAL breast tumors. Both RAL and TAM were agonists on the growth of MCF7RAL tumors, and there was no significant difference between the 2 SERMs (p=.2). ICI exhibited no agonistic properties and was effective in blocking the effects of postmenopausal E2 on the growth of MCF7RAL tumors (p=.0006). The MCF7RAL tumors were grade 3 by H&E staining, and were ERα-positive. With prolonged RAL exposure, the tumors were only weakly ER-α positive Conclusion: RAL stimulates the growth of high grade ERα-positive breast tumors in vivo . RAL and TAM are cross-resistant on the growth of RAL-stimulated breast tumors in vivo. Therefore, in patients who develop breast cancer on RAL, TAM is unlikely to be effective and treament with ICI or an aromatase inhibitor should be considered as first-line treatment.
|Original language||English (US)|
|Number of pages||1|
|Journal||Breast Cancer Research and Treatment|
|State||Published - Jan 1 2001|
ASJC Scopus subject areas
- Cancer Research