Mrs Rekha is a 42-yrs-old, is diagnosed with metastatic breast cancer. You consider use of tamoxifen, raloxifene, toremifene, or fulvestrant. Why might fulvestrant be the best choice, all other factors being equal? (AIPG 2009)
|A||Exerts antiplatelet, rather than thrombotic, effects|
|B||Lacks ability to cause hot flashes or other disturbing side effects|
|C||Lower risk of causing endometrial cancer|
|D||Provides clinical cure, rather than palliation, in all patients|
a. Fulvestrant is associated with a much lower risk of causing endometrial pathology, including cancer. It is a “pure” estrogen antagonist. That effect, in breast tissue, is what accounts for the drug’s beneficial effects in some patients with metastatic, estrogen-supported, breast cancer. In contrast, tamoxifen, raloxifene, and toremifene are classified as selective estrogen receptor modifiers (SERMs).
b. Although they block estrogen receptors in breast tissue (just as fulvestrant does), they also have estrogenic (agonist) activity in some other tissues, notably the uterus. There they can cause endometrial proliferation, hyperplasia, and (apparently) an increased risk of endometrial cancer.
c. Because fulvestrant lacks estrogen agonist activity, it will not enhance bone mineralization nor favorably modify cholesterol profiles, as the SERMs tend to do. The SERMs slightly increase the risk of thromboembolism. Fulvestrant may too, but it also lacks any ability to prevent platelet aggregation or thromboembolism. Hot flashes are fairly common with any of these drugs.