Hot Flashes in Patients Taking Tamoxifen

  • Tamoxifen:
    • Is indicated for premenopausal patients with:
      • Node-negative, hormone receptor–positive, HER2-negative breast cancer with low-risk recurrence scores
    • Is a selective estrogen receptor modulator (SERM):
      • With antiestrogenic activity in breast tissue:
        • Reducing epithelial cell proliferation
  • Hot flashes are one of the most common and bothersome side effects of tamoxifen:
    • Up to 80% of women prescribed tamoxifen complain of hot flashes:
      • About 30% rate them as severe
    • Premenopausal women have a greater increase in hot flashes after starting tamoxifen compared with perimenopausal or postmenopausal women
    • Hot flashes are believed to be due to a central nervous system antiestrogenic effect:
      • Causing thermoregulatory dysfunction
    • Additionally, some data suggest that polymorphisms in drug metabolizing enzymes (cytochrome P450 enzyme, CYP2D6):
      • Decrease the conversion of tamoxifen to its most active metabolite (endoxifen):
        • They may influence the likelihood of tamoxifen-related hot flashes
      • Co administration of drugs that inhibit the activity of CYP2D6:
        • Such as the selective serotonin reuptake inhibitors (SSRIs):
          • Can reduce tamoxifen-related hot flashes
          • Among SSRIs, there is a gradient of potency for inhibition of CYP2D6:
            • For example, paroxetine and fluoxetine are strong CYP2D6 inhibitors, while sertraline and duloxetine are moderate inhibitors.
            • While the strong CYP2D6 inhibitors have the potential to adversely affect drug efficacy, the data to suggest that this issue decreases tamoxifen effect are very weak
            • Venlafaxine is a weak CYP2D6 inhibitor with proven efficacy against hot flashes without risk of significantly interfering with tamoxifen metabolism
  • Black cohosh:
    • Is a substance with purported efficacy treating menopausal symptoms:
      • It is not FDA regulated with reported rare incidence of hepatotoxicity
    • Its use would be contraindicated in a patient on tamoxifen:
      • As it may interfere with CYP2D6 activity
  • References:
  • Aiello Bowles EJ, Boudreau DM, Chubak J, Yu O, Fujii M, Chestnut J, Buist DS. Patient-reported discontinuation of endocrine therapy and related adverse effects among women with early-stage breast cancer. J Oncol Pract. 2012;8(6):e149-e157.
  • Ramaswami R, Villarreal MD, Pitta DM, Carpenter JS, Stebbing J, Kalesan B. Venlafaxine in management of hot flashes in women with breast cancer: a systematic review and meta-analysis. Breast Cancer Res Treat. 2015;152(2):231-237.
  • Johns C, Seav SM, Dominick SA, Gorman JR, Li H, Natarajan L, Mao JJ, et al. Informing hot flash treatment decisions for breast cancer survivors: a systematic review of randomized trials comparing active interventions. Breast Cancer Res Treat. 2016;156(3):415-426.

#Arrangoiz #BreastSurgeon #CancerSurgeon #SurgicalOncologist #BreastCancer #Tamoxifen #Hotflashes #EndocrineTherapy #CASO #CenterforAdvancedSurgicalOncology

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