Can other drugs interfere with hormone therapy?
Certain drugs, including several commonly prescribed antidepressants (those in the category called selective serotonin reuptake inhibitors, or SSRIs), inhibit an enzyme called CYP2D6. This enzyme plays a critical role in the use of tamoxifen by the body because it metabolizes, or breaks down, tamoxifen into molecules, or metabolites, that are much more active than tamoxifen itself.
The possibility that SSRIs might, by inhibiting CYP2D6, slow the metabolism of tamoxifen and reduce its potency is a concern given that as many as one-fourth of breast cancer patients experience clinical depression and may be treated with SSRIs. In addition, SSRIs are sometimes used to treat hot flashes caused by hormone therapy.
Researchers have found that women taking certain SSRIs together with tamoxifen have decreased blood levels of active tamoxifen metabolites. Because of this, many experts suggest that patients who are taking antidepressants along with tamoxifen should discuss treatment options with their doctors. For example, doctors may recommend switching from an SSRI that is a potent inhibitor of CYP2D6 (such as paroxetine) to one that is a weaker inhibitor (such as sertraline) or that has no inhibitory activity (such as venlafaxine or citalopram), or they may suggest that their postmenopausal patients take an aromatase inhibitor instead of tamoxifen.
Other medications that inhibit CYP2D6 include the following:
- Quinidine, which is used to treat abnormal heart rhythms
- Diphenhydramine, which is an antihistamine
- Cimetidine, which is used to reduce stomach acid
People who are prescribed tamoxifen should discuss the use of all other medications with their doctors.
Where can someone find more information about drugs used in hormone therapy for breast cancer?
NCI’s Drug Information Summaries provide consumer-friendly information about certain drugs that are approved by the FDA to treat cancer or conditions related to cancer. For each drug, topics covered include background information, research results, possible side effects, FDA approval information, and ongoing clinical trials. The Drug Information Summaries include information about drugs that have been approved for breast cancer.
1. Dunnwald LK, Rossing MA, Li CI. Hormone receptor status, tumor characteristics, and prognosis: a prospective cohort of breast cancer patients. Breast Cancer Research 2007; 9(1):R6.
2. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 2011; 378(9793)771–784.
3. Untch M, Thomssen C. Clinical practice decisions in endocrine therapy. Cancer Investigation 2010; 28 Suppl 1:4–13.
4. Regan MM, Neven P, Giobbie-Hurder A, et al. Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1–98 randomised clinical trial at 8.1 years median follow-up. Lancet Oncology 2011; 12(12):1101–1108.
5. Burstein HJ, Griggs JJ. Adjuvant hormonal therapy for early-stage breast cancer. Surgical Oncology Clinics of North America 2010; 19(3):639–647.
6. Sawka CA, Pritchard KI, Shelley W, et al. A randomized crossover trial of tamoxifen versus ovarian ablation for metastatic breast cancer in premenopausal women: a report of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) trial MA.1. Breast Cancer Research and Treatment 1997; 44(3):211–215.
7. Howell A, Pippen J, Elledge RM, et al. Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma: a prospectively planned combined survival analysis of two multicenter trials. Cancer 2005; 104(2):236–239.
8. Cuzick J, Sestak I, Baum M, et al. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncology 2010; 11(12):1135–1141.
9. Mouridsen H, Gershanovich M, Sun Y, et al. Phase III study of letrozole versus tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: analysis of survival and update of efficacy from the International Letrozole Breast Cancer Group. Journal of Clinical Oncology 2003; 21(11):2101–2109.
10. Mauri D, Pavlidis N, Polyzos NP, Ioannidis JP. Survival with aromatase inhibitors and inactivators versus standard hormonal therapy in advanced breast cancer: meta-analysis. Journal of the National Cancer Institute 2006; 98(18):1285–1291.
11. Chia YH, Ellis MJ, Ma CX. Neoadjuvant endocrine therapy in primary breast cancer: indications and use as a research tool. British Journal of Cancer 2010; 103(6):759–764.
12. Vogel VG, Costantino JP, Wickerham DL, et al. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P–2 trial. JAMA 2006; 295(23):2727–2741.
13. Vogel VG, Costantino JP, Wickerham DL, et al. Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P–2 Trial: preventing breast cancer. Cancer Prevention Research 2010; 3(6):696–706.
14. Goss PE, Ingle JN, Alés-Martinez JE, et al. Exemestane for breast-cancer prevention in postmenopausal women. New England Journal of Medicine 2011; 364(25):2381–2391.
15. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P–1 Study. Journal of the National Cancer Institute 1998; 90(18):1371–1388.
16. Gorin MB, Day R, Costantino JP, et al. Long-term tamoxifen citrate use and potential ocular toxicity. American Journal of Ophthalmology 1998; 125(4):493–501.
17. Tamoxifen for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists’ Collaborative Group. Lancet 1998; 351(9114):1451–1467.
18. Amir E, Seruga B, Niraula S, Carlsson L, Ocaña A. Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients: a systematic review and meta-analysis. Journal of the National Cancer Institute 2011; 103(17):1299–1309.
19. Coates AS, Keshaviah A, Thürlimann B, et al. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1–98. Journal of Clinical Oncology 2007; 25(5):486–492.
20. Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists’ Group. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncology 2008; 9(1):45–53.
21. Coombes RC, Kilburn LS, Snowdon CF, et al. Survival and safety of exemestane versus tamoxifen after 2–3 years’ tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet 2007; 369(9561):559–570. Erratum in: Lancet 2007; 369(9565):906.
22. Boccardo F, Rubagotti A, Guglielmini P, et al. Switching to anastrozole versus continued tamoxifen treatment of early breast cancer. Updated results of the Italian Tamoxifen Anastrozole (ITA) Trial. Annals of Oncology 2006; 17(Suppl 7):vii10–vii14.
23. Osborne CK, Pippen J, Jones SE, et al. Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial. Journal of Clinical Oncology 2002; 20(16):3386–3395.
Source: National Cancer Institute