A 60-year-old woman comes to the office for a breast cancer follow-up visit. The patient recently underwent a right mastectomy for a node-negative, estrogen- and progesterone-receptor-positive tumor. She was started on an aromatase inhibitor for adjuvant therapy; however, the medication was discontinued due to severe fatigue and poor sleep. As a result, she is scheduled to begin a 5-year course of adjuvant therapy with tamoxifen. The patient has no other chronic medical conditions and her only medication is a daily multivitamin. Her last menstrual period was 5 years ago. The patient's father had a myocardial infarction at age 65; family history is otherwise noncontributory. She does not use tobacco, alcohol, or illicit drugs. Vital signs are stable. BMI is 21 kg/m². The patient has many concerns about tamoxifen therapy and asks about potential side effects. Which of the following is the patient at greatest risk for developing due to tamoxifen therapy?

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11ec25c8_d9a7_ea40_bc81_cd4e9eee4399_MD0003_00 Adjuvant endocrine therapy is commonly used for the treatment of nonmetastatic, hormone-receptor-positive breast cancer. The most commonly used endocrine agents include tamoxifen, aromatase inhibitors, and ovarian suppression (eg, GnRH agonists or surgery). Tamoxifen is a selective estrogen receptor modulator that is an estrogen receptor antagonist in the breast. It is the preferred adjuvant treatment for premenopausal women at low risk of breast cancer recurrence. Tamoxifen is also a second-line endocrine adjuvant agent for postmenopausal women who cannot use aromatase inhibitor therapy (eg, intolerable side effects). Tamoxifen acts as an estrogen agonist in the uterus that can stimulate excessive endometrial proliferation. Therefore, tamoxifen use is associated with endometrial polyps in premenopausal women as well as endometrial hyperplasia and cancer in postmenopausal women. These risks continue for the duration of therapy and resolve after discontinuation of treatment. However, the benefit of improved survival from breast cancer due to tamoxifen outweighs the risk of endometrial cancer. endometrial polyps (Choice A) In postmenopausal women, tamoxifen has some estrogen-like activity on the bone, which can increase bone mineral density and significantly reduce the incidence of osteoporosis. However, tamoxifen is generally not a first-line agent for osteoporosis treatment due to the risk of endometrial cancer. (Choice B) Dysplasia of the cervical transformation zone is typically caused by chronic human papillomavirus infection. Tamoxifen has no known effects on the cervix. (Choice C) Tamoxifen is not associated with an increased risk for adenomyosis (ectopic endometrial tissue in the myometrium). (Choice E) Intimal thickening of the coronary arteries is a precursor lesion for atherosclerosis. Tamoxifen decreases the blood cholesterol level and may protect against coronary artery disease. Educational objective: Tamoxifen is an estrogen antagonist on breast tissue and is used in the treatment and prevention of breast cancer. Tamoxifen is an estrogen agonist in the uterus and increases the risk of endometrial polyps, hyperplasia, and cancer. References: Selective estrogen receptor modulators in clinical practice: a safety overview. (http://www.ncbi.nlm.nih.gov/pubmed/25936229) ACOG practice bulletin no. 126: management of gynecologic issues in women with breast cancer. (http://www.ncbi.nlm.nih.gov/pubmed/22353976)

A 60-Year-Old Woman Comes to the Office for a Breast