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aromatase inhibitor

Indications: - treatment of estrogen receptor-positive status breast cancer in postmenopausal women - aromatase inhibitors lower breast cancer recurrence in postmenopausal women relative to tamoxifen by 30% [8] - aromatase inhibitors lower breast cancer mortality in postmenopausal women relative to tamoxifen [8] - treatment of ovarian cancer [2] Contraindications: - ESR1 mutations Radiology: - serial bone mineral density every other year [1] Adverse effects: 1) see specific aromatase inhibitor 2) osteoporosis resulting in pathologic fracture [1] - evaluated fracture risk in all women starting aromatase inhibitor [10] - bisphosphate or other therapy for women with T-score T-score < -1.5 SD + 1 other fracture risk factor (i.e. age >65 or low body-mass index) or > 1 risk factor. - zoledronate yearly or denosumab every 6 months [4,10] - oral bisphosphonate may be less effective [10] 3) joint pain, musculoskeletal pain (arthralgias & myalgias) [5] may be caused by diminished estrogen levels; estrogen is thought to have anti-inflammatory properties & to inhibit pain signals - clinically significant musculoskeletal complications develop in ~50% of women treated with aromatase inhibitors [11] - development of musculoskeletal pain & arthragias during treatment is linked to better breast cancer outcomes [11] - a 2nd aromatase inhibitor should be tried if patient develops severe musculoskeletal symptoms [1] - duloxetine & exercise may be of benefit [1] - if musculoskeletal symptoms persist, tamoxifen should be tried [1] - acupuncture 2 sesson/week for 6 weeks of benefit [12] 4) vaginal dryness (20%) [2] a) safety of vaginal estrogens not known b) systemic absorption occurs with use of vaginal estrogens 1] tends to decrease as therapy continues 2] absorption highes with creams, lowest with Estrig c) vaginal lubricants (Astroglide, Replens, Lubrin) safer than vaginal estrogens 5) ovarian stimulation in premenopausal women 6) fatigue, anxiety, depression - acupuncture may be of some benefit [7] 7) ESR1 gene mutations confer resistance to aromatase inhibitors - occur most frequently on exposure to aromatase inhibitors [13]

Interactions

drug adverse effects of aromatase inhibitors

Specific

anastrozole (Arimidex) exemestane (Aromasin) letrozole (Femara) metandroden (Atamestane) testolactone (Teslac, Fludestrin)

General

antineoplastic endocrine agent enzyme inhibitor estrogen antagonist

Properties

INHIBITS: cytochrome P450 19A1

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 16, 17, 19. American College of Physicians, Philadelphia 2012, 2015, 2019
  2. Prescriber's Letter 13(5): 2006 Aromatase inhibitors and vaginal estrogen Detail-Document#: 220516 (subscription needed) http://www.prescribersletter.com
  3. Becker T, Lipscombe L, Narod S, et al. Systematic review of bone health in older women treated with aromatase inhibitors for early-stage breast cancer. J Am Geriatr Soc. 2012 Sep;60(9):1761-1767. PMID: 22985145
  4. Coleman R, de Boer R, Eidtmann H et al Zoledronic acid (zoledronate) for postmenopausal women with early breast cancer receiving adjuvant letrozole (ZO-FAST study): final 60-month results. Ann Oncol. 2013 Feb;24(2):398-405. PMID: 23047045 - Llombart A, Frassoldati A, Paija O, Immediate Administration of Zoledronic Acid Reduces Aromatase Inhibitor-Associated Bone Loss in Postmenopausal Women With Early Breast Cancer: 12-month analysis of the E-ZO-FAST trial. Clin Breast Cancer. 2012 Feb;12(1):40-8. PMID: 22014381
  5. Prescriber's Letter 12(9): 2005 Aromatase inhibitors & the Risk of Arthralgias Detail-Document#: 211019 (subscription needed) http://www.prescribersletter.com
  6. Deprecated Reference
  7. Mao JJ et al Electroacupuncture for fatigue, sleep, and psychological distress in breast cancer patients with aromatase inhibitor- related arthralgia: A randomized trial. Cancer. Online July 30, 2014 PMID: 25077452 http://onlinelibrary.wiley.com/doi/10.1002/cncr.28917/abstract
  8. Early Breast Cancer Trialists' Collaborative Group (EBCTCG) Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet. Published Online: 23 July 2015 PMID: 26211827 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2815%2961074-1/abstract - Mayer EL, Burstein HJ Postmenopausal breast cancer: a best endocrine strategy? Lancet. Published Online: 23 July 2015 PMID: 26211823 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2815%2961206-5/abstract
  9. Henry NL, Azzouz F, Desta Z et al Predictors of aromatase inhibitor discontinuation as a result of treatment-emergent symptoms in early-stage breast cancer. J Clin Oncol. 2012 Mar 20;30(9):936-42 PMID: 22331951
  10. Hadji P, Aaprob MS, Body JJ et al Management of Aromatase Inhibitor-Associated Bone Loss (AIBL) in postmenopausal women with hormone sensitive breast cancer: Joint position statement of the IOF, CABS, ECTS, IEG, ESCEO, IMS, and SIOG. J Bone Oncol. 2017 Mar 23;7:1-12. eCollection 2017 Jun. Review PMID: 28413771 Free PMC Article http://www.sciencedirect.com/science/article/pii/S2212137417300258 - International Osteoporosis Foundation Public Release: 25-Apr-2017 New guidance for management of aromatase-inhibitor related bone loss in breast cancer. https://www.eurekalert.org/pub_releases/2017-04/iof-ngf042517.php
  11. Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022 - Tenti S, Correale P, Cheleschi S, et al. Aromatase inhibitors-induced musculoskeletal disorders: current knowledge on clinical and molecular aspects. Int J Mol Sci. 2020;21(16):5625 PMID: 32781535 PMCID: PMC7460580 Free PMC article https://www.mdpi.com/1422-0067/21/16/5625
  12. Hershman DL, Unger JM, Greenlee H et al Comparison of Acupuncture vs Sham Acupuncture or Waiting List Control in the Treatment of Aromatase Inhibitor-Related Joint Pain. A Randomized Clinical Trial. JAMA Netw Open. 2022;5(11):e2241720 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2798317
  13. Tan WW, Marienberg ES Fast Five Quiz: Precision Medicine in Cancer Medscape. January 06, 2023 https://reference.medscape.com/viewarticle/954083