- Tamoxifen is indicated for:
- Premenopausal patients with:
- Node-negative, hormone receptor–positive, HER2-negative breast cancer with low-risk recurrence scores
- Premenopausal patients with:
- Tamoxifen:
- Is a selective estrogen receptor modulator (SERM) with antiestrogenic activity in breast tissue:
- Reducing epithelial cell proliferation
- Is a selective estrogen receptor modulator (SERM) with antiestrogenic activity in breast tissue:
- 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
- A central nervous system antiestrogenic effect:
- 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), and they may influence the likelihood of tamoxifen-related hot flashes
- Cytochrome P450 enzyme, CYP2D6):
- Coadministration 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
- Such as the selective serotonin reuptake inhibitors (SSRIs):
- Up to 80% of women prescribed tamoxifen complain of hot flashes:
- 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
1. 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.
2. 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.
3. 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.
Rodrigo Arrangoiz MS, MD, FACS, FSSO 