Aromatase inhibitors (AIs) are indicated in the treatment of hormone-receptive breast cancer in postmenopausal women in various settings. Studies have shown that they are effective when used as adjuvant therapy to chemotherapy and surgery in metastatic estrogen-dependent breast cancer. Their use in preventative and adjuvant therapies for other conditions is currently under investigation.
FDA approved indications:
FDA non-approved indications:
Aromatase inhibitors (AIs) inhibit the action of the enzyme aromatase. Aromatase (estrogen synthetase) is a member of the cytochrome P450 superfamily of monooxygenases and catalyzes the demethylation of androgens' carbon 19, producing phenolic 18-carbon estrogens. In the case of postmenopausal women, the conversion of androgens to estrogens via this pathway in the adrenal glands, the skin, the muscle, and the adipose tissue, is the primary source of estrogen. Aromatase inhibitors block this pathway and consequently suppress estrogen levels in postmenopausal women. The breast cancer cells also demonstrate aromatase activity, a likely source of local estrogen for the tumor cells. The inhibition or inactivation of aromatase suppresses serum estrogen levels, which decrease estrogen-mediated cancer cell proliferation in hormone receptor-positive breast cancer.
In premenopausal women, AIs induce an increase in gonadotropin secretion secondary to the reduced negative feedback of estrogen to the pituitary, resulting in ovarian stimulation. Clinicians can use AIs to induce ovulation in the treatment of infertility. Aromatase activity increases in endometriosis with extrauterine endometrial tissue acting as a source of estrogens. Estrogen stimulates the synthesis of PGE2, which causes increased aromatase activity in the endometrium. This vicious cycle leads to the growth of ectopic endometrial tissue, which is blocked by aromatase inhibitors by inhibiting the synthesis of estrogen in extrauterine endometrial tissue.
In men, estrogen excess shows an association with premature closure of the epiphyses. Aromatase inhibitors decrease estrogen by inhibiting the conversion of testosterone to estrogen and has therefore been used in patients with short stature and/or constitutional delay of puberty. Lowering estrogen levels is associated with an increase in LH, FSH, and testosterone. Therefore aromatase inhibitors have also been used in late-onset hypogonadism or partial androgen deficiency. In obese men, there is an increased conversion of androgens to estrogen in the adipose tissue, leading to increased estrogen levels. Aromatase inhibitors also decrease this conversion causing decreased estrogen and increased testosterone and FSH in men with obesity-related hypogonadotropic hypogonadism and male subfertility.
Anastrozole is available as a 1 mg tablet, which is to be taken orally once a day, with or without food. No dose adjustment is necessary for patients with renal or liver impairment or elderly patients. The American Society of Clinical Oncology recommends the use of aromatase inhibitors as a component of adjuvant hormonal therapy after surgery for ten years in postmenopausal patients who have a diagnosis of early-stage, node-positive, and hormone receptive breast cancer.
Various adverse reactions can happen with aromatase inhibitors. (Seen in less than 1 in 10,000 patients). Some of them are as follows:
Common adverse reactions (10% incidence) include the following: hot flashes, asthenia, joint disorders such as arthritis or arthralgia, osteoporosis, fractures, bone pain, back pain, vaginal dryness, dyspareunia, sexual dysfunction, uterine atrophy, hypertension, hyperlipidemia, hypercholesterolemia, thromboembolic disease, cardiac and cerebrovascular events, insomnia, nausea.
The most common reason for discontinuing aromatase inhibitor therapy is the development of arthralgias, known as aromatase inhibitor-associated arthralgia syndrome. Patients will present with joint pain and mild swelling in the absence of other systemic diseases or other causes. The deficiency of estrogen causes a decrease in bone mineral density, which contributes to joint pain. Estrogen also shows links to the regulation of cytokine activity as well as the modulation of pain reception in the nervous system.
There are two major contraindications to aromatase inhibitors.
All patients on aromatase inhibitors should have initial routine lab work including a complete blood count, serum calcium, vitamin D levels, lipid profile, and liver function tests. Patients should also have a baseline bone mineral density test (DEXA scan) before the initiation of the treatment.
Clinical trials have shown aromatase inhibitors were well tolerated, even at high doses. There is no established dose of aromatase inhibitors considered as life-threatening. There is no specific treatment for the overdose of this class of medications. Standard treatment of care, such as frequent vital sign checks, induced emesis, and management of symptoms, is recommended.
Interprofessional communication between healthcare teams is essential, especially in the management of cancer patients. Every professional has a vital role to play. Oncologists should select the treatment regimen based on the guidelines after thoroughly assessing the patient factors. For example, in hormone receptor-negative breast cancer or premenopausal patients with breast cancer, aromatase inhibitors may not be appropriate. Physicians and nurses should be concerned enough for the adverse effects of long term therapy with aromatase inhibitors, especially osteoporosis and hyperlipidemia. Pharmacists should evaluate the patient's medication history to prevent any drug interactions, especially with tamoxifen and warfarin. Case management should include counseling regarding improving bone health and early initiation of bisphosphonates in the case of osteopenia. [Level 5]
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