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 effectiveness 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.
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 hydrochloride (Paxil®), to one that is a weaker inhibitor, such assertraline (Zoloft®), or that has no inhibitory activity, such as venlafaxine (Effexor®) or citalopram (Celexa®). 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.
1. Kohler BA, Sherman RL, Howlader N, et al. Annual Report to the Nation on the Status of Cancer, 1975-2011, featuring incidence of breast cancer subtypes by race/ethnicity, poverty, and state. Journal of the National Cancer Institute 2015; 107(6):djv048. doi: 10.1093/jnci/djv048
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. [PubMed Abstract]
3. Untch M, Thomssen C. Clinical practice decisions in endocrine therapy. Cancer Investigation 2010; 28 Suppl 1:4–13. [PubMed Abstract]
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. [PubMed Abstract]
5. Burstein HJ, Griggs JJ. Adjuvant hormonal therapy for early-stage breast cancer. Surgical Oncology Clinics of North America 2010; 19(3):639–647. [PubMed Abstract]
6. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), Dowsett M, Forbes JF, et al. Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet 2015; 386(10001):1341-1352. [PubMed Abstract]
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. [PubMed Abstract]
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. [PubMed Abstract]
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. [PubMed Abstract]
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. [PubMed Abstract]
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. [PubMed Abstract]
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. [PubMed Abstract]
13. Cuzick J, Sestak I, Cawthorn S, et al. Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial. Lancet Oncology 2015; 16(1):67-75. [PubMed Abstract]
14. 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. [PubMed Abstract]
15. 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. [PubMed Abstract]
16. Cuzick J, Sestak I, Forbes JF, et al. Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial. Lancet 2014; 383(9922):1041-1048. [PubMed Abstract]
17. 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. [PubMed Abstract]
18. 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. [PubMed Abstract]
19. Tamoxifen for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists’ Collaborative Group. Lancet 1998; 351(9114):1451–1467. [PubMed Abstract]
20. 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. [PubMed Abstract]
21. 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. [PubMed Abstract]
22. 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. [PubMed Abstract]
23. 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. [PubMed Abstract]
24. 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. [PubMed Abstract]
25. 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. [PubMed Abstract]
Source: National Cancer Institute.