A 48-year-old woman, gravida 3 para 3, comes to the office for a follow-up visit due to a history of stage I hormone receptor-positive lobular breast carcinoma. She was diagnosed using needle-guided biopsy after a screening mammogram revealed irregular densities. The patient's condition was treated with mastectomy, radiation therapy, and adjuvant chemotherapy. She also has a history of hypertension and hyperlipidemia, which are controlled with daily medications. The patient quit smoking after the cancer diagnosis and tries to exercise 3 times a week. She is prescribed tamoxifen therapy for an anticipated duration of at least 5 years. As a result of tamoxifen initiation, this patient is at greatest risk for developing which of the following?

Question

A 48-year-old woman, gravida 3 para 3, comes to the office for a follow-up visit due to a history of stage I hormone receptor-positive lobular breast carcinoma.  She was diagnosed using needle-guided biopsy after a screening mammogram revealed irregular densities.  The patient's condition was treated with mastectomy, radiation therapy, and adjuvant chemotherapy.  She also has a history of hypertension and hyperlipidemia, which are controlled with daily medications.  The patient quit smoking after the cancer diagnosis and tries to exercise 3 times a week.  She is prescribed tamoxifen therapy for an anticipated duration of at least 5 years.  As a result of tamoxifen initiation, this patient is at greatest risk for developing which of the following?

Quizplus · Accepted Answer

11ec25c8_d9a8_8681_bc81_bfc02a55d452_MD0003_00 Tamoxifen and raloxifene are commonly used selective estrogen receptor modulators. These drugs exhibit estrogen agonist and antagonist activity in a tissue-specific fashion. Tamoxifen is an estrogen antagonist in the breast and is therefore used as adjuvant therapy for estrogen receptor-positive breast cancer. It also reduces the risk for breast cancer recurrence and the development of new cancer in the opposite breast. Hot flashes are the most common adverse effect, experienced by up to 80% of patients taking tamoxifen. Tamoxifen is theorized to exhibit antiestrogenic activity in the CNS and to cause thermoregulatory dysfunction in the anterior hypothalamus via a mechanism similar to the pathophysiology of menopausal hot flashes. Additional adverse effects (related to estrogenic activity) include thromboembolism, endometrial cancer, and uterine sarcoma. (Choice A) The greatest risk factor for cervical dysplasia is persistent infection with oncogenic strains of human papillomavirus (eg, types 16, 18); tamoxifen does not cause cervical dysplasia. (Choice B) This patient has several risk factors for coronary heart disease (eg, hypertension, hyperlipidemia, prior tobacco use), but tamoxifen use does not appear to impact that risk. Tamoxifen does decrease blood lipid levels. (Choice C) Tamoxifen is an estrogen agonist in the uterus, which can lead to endometrial proliferation (ie, reversal of endometrial atrophy) in postmenopausal patients and increased risk for endometrial hyperplasia and cancer. In premenopausal patients, tamoxifen use increases the risk for endometrial polyps. It can also stimulate uterine leiomyoma and is a risk factor for malignant uterine sarcoma development. endometrial polyps (Choice E) Estrogens (eg, estrogen-containing oral contraceptives) and mixed estrogen agonists (eg, tamoxifen, raloxifene) increase protein C resistance. Therefore, patients are at increased risk for venous thromboembolism; bruising is unlikely. (Choice F) Risk factors for ovarian cancer include a family history of ovarian cancer (eg, BRCA gene mutation, Lynch syndrome) and nulliparity. Preliminary data show that tamoxifen use may decrease the risk for ovarian cancer. Educational objective: Tamoxifen is used for adjuvant therapy in hormone-positive breast cancer and has mixed agonist and antagonist activity on estrogen receptors. Hot flashes are the most common adverse effect. Tamoxifen use also increases the risk for endometrial cancer, uterine sarcoma, and venous thromboembolism. References: Gynecologic conditions in participants in the NSABP breast cancer prevention study of tamoxifen and raloxifene (STAR). (http://www.ncbi.nlm.nih.gov/pubmed/21872200) The effect of tamoxifen on the genital tract. (http://www.ncbi.nlm.nih.gov/pubmed/18603495)

A 48-Year-Old Woman, Gravida 3 Para 3, Comes to the Office