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Decreased risk of endometrial cancer
71%
32/45
Increased risk of deep vein thrombosis
2%
1/45
Induction of menopausal symptoms
11%
5/45
Decreased risk of osteoporosis
9%
4/45
Increased risk of ocular toxicity
4%
2/45
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Tamoxifen causes an increased risk of endometrial cancer due to its agonist activity on estrogen receptors in endometrial tissue. Tamoxifen is a selective estrogen receptor modulator (SERM) whose efficacy in treating breast cancer is due to antagonistic activity at estrogen receptors in the malignancy. Tamoxifen also acts as an agonist in bone, leading to decreased risks of osteoporosis. The major difference between tamoxifen and raloxifene, another SERM used to treat breast cancer, is that raloxifene acts as an estrogen receptor antagonist in endometrial tissue. Therefore, while tamoxifen increases the risk of endometrial cancer, raloxifene is protective against endometrial cancer. Maughan et al. review the treatment of breast cancer. They note that stage I and II breast cancer can typically be treated with breast-conserving surgical approaches, followed by radiation. In contrast, treatment of lymph-node positive cancer usually also includes chemotherapy, hormonal therapy, or trastuzumab (anti-ERBB2). Thurlimann et al. perform a large-scale, randomized, double-blind, controlled trial to compare tamoxifen to letrizole for treatment of hormone-receptor positive breast cancer in postmenopausal women. Letrizole is an aromatase inhibitor that was shown to be efficacious in previous trial phases. They conclude that letrizole is superior to tamoxifen, most notably in preventing distant metastases. Illustration A shows an invasive ductal carcinoma on mammogram. Illustration B shows a papillary carcinoma of the breast on mammogram. Incorrect Answers: Answer 2: Tamoxifen is associated with an increased risk of deep venous thrombosis. Answer 3: Tamoxifen use causes earlier onset of menopausal symptoms. Answer 4: Tamoxifen is an estrogen agonist at bone and has protective effects against osteoporosis. Answer 5: Tamoxifen causes an increased risk of ocular toxicity, including retinopathy, optic neuritis, and cataracts.
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