Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients: a systematic review and meta-analysis - PubMed (original) (raw)
Review
. 2011 Sep 7;103(17):1299-309.
doi: 10.1093/jnci/djr242. Epub 2011 Jul 9.
Affiliations
- PMID: 21743022
- DOI: 10.1093/jnci/djr242
Review
Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients: a systematic review and meta-analysis
Eitan Amir et al. J Natl Cancer Inst. 2011.
Abstract
Background: Aromatase inhibitors are associated with consistent improvements in disease-free survival but not in overall survival. We conducted a literature-based meta-analysis of randomized trials to examine whether the relative toxicity of aromatase inhibitors compared with tamoxifen may explain this finding.
Methods: We conducted a systematic review to identify randomized controlled trials that compared aromatase inhibitors and tamoxifen as primary adjuvant endocrine therapy in postmenopausal women by searching MEDLINE, EMBASE, and databases of the American Society of Clinical Oncology and San Antonio Breast Cancer Symposium. Odds ratios (ORs), 95% confidence intervals (CIs), absolute risks, and the number needed to harm associated with one adverse event were computed for prespecified serious adverse events including cardiovascular disease, cerebrovascular disease, bone fractures, thromboembolic events, endometrial carcinoma and other second cancers not including new breast cancer. All statistical tests were two-sided.
Results: Seven trials enrolling 30,023 patients met the inclusion criteria. Longer duration of aromatase inhibitor use was associated with increased odds of developing cardiovascular disease (OR = 1.26, 95% CI = 1.10 to 1.43, P < .001; number needed to harm = 132) and bone fractures (OR = 1.47, 95% CI = 1.34 to 1.61, P < .001; number needed to harm = 46), but a decreased odds of venous thrombosis (OR = 0.55, 95% CI = 0.46 to 0.64, P < .001; number needed to harm = 79) and endometrial carcinoma (OR = 0.34, 95% CI = 0.22 to 0.53, P < .001; number needed to harm = 258). Five years of aromatase inhibitors was associated with a non-statistically significant increased odds of death without recurrence compared with 5 years of tamoxifen alone or tamoxifen for 2-3 years followed by an aromatase inhibitor for 2-3 years (OR = 1.11, 95% CI = 0.98 to 1.26, P = .09).
Conclusions: The cumulative toxicity of aromatase inhibitors when used as up-front treatment may explain the lack of overall survival benefit despite improvements in disease-free survival. Switching from tamoxifen to aromatase inhibitors reduces this toxicity and is likely the best balance between efficacy and toxicity.
Similar articles
- Aromatase inhibitors in adjuvant therapy for hormone receptor positive breast cancer: a systematic review.
Eisen A, Trudeau M, Shelley W, Messersmith H, Pritchard KI. Eisen A, et al. Cancer Treat Rev. 2008 Apr;34(2):157-74. doi: 10.1016/j.ctrv.2007.11.001. Epub 2007 Dec 31. Cancer Treat Rev. 2008. PMID: 18164821 Review. - Postmenopausal women with hormone receptor-positive breast cancer: balancing benefit and toxicity from aromatase inhibitors.
Ingle JN. Ingle JN. Breast. 2013 Aug;22 Suppl 2:S180-3. doi: 10.1016/j.breast.2013.07.035. Breast. 2013. PMID: 24074784 Review. - Evolution in the risk of adverse events of adjuvant endocrine therapy in postmenopausal women with early-stage breast cancer.
Reinhorn D, Yerushalmi R, Moore A, Desnoyers A, Saleh RR, Amir E, Goldvaser H. Reinhorn D, et al. Breast Cancer Res Treat. 2020 Jul;182(2):259-266. doi: 10.1007/s10549-020-05715-1. Epub 2020 Jun 1. Breast Cancer Res Treat. 2020. PMID: 32488391 Review. - A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer.
Breast International Group (BIG) 1-98 Collaborative Group; Thürlimann B, Keshaviah A, Coates AS, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Rabaglio M, Smith I, Wardley A, Price KN, Goldhirsch A. Breast International Group (BIG) 1-98 Collaborative Group, et al. N Engl J Med. 2005 Dec 29;353(26):2747-57. doi: 10.1056/NEJMoa052258. N Engl J Med. 2005. PMID: 16382061 Clinical Trial.
Cited by
- Efficacy and safety of adjuvant therapies in older patients with breast cancer: a systematic review and meta-analysis of real-world data.
Chen YA, Lai HW, Su HC, Loh EW, Huang TW, Tam KW. Chen YA, et al. Breast Cancer. 2024 Sep;31(5):739-753. doi: 10.1007/s12282-024-01622-1. Epub 2024 Aug 1. Breast Cancer. 2024. PMID: 39085679 Review. - Quality of life in women with early-stage and metastatic hormone receptor-positive, HER2-negative breast cancer receiving endocrine therapy.
O'Reilly D, Farooq AR, Nevins Selvadurai P, Sheehan L, Molan K, Krishnanivas B, Mullen V, McMahon D, Hadi D, Ahmed A, Jennings M, Carroll H, Chew S, Macanovic B, O'Hanlon Brown C, Noonan SA, O Reilly S, Connolly RM, Cahir C, Kelly CM. O'Reilly D, et al. Oncologist. 2024 Oct 3;29(10):842-849. doi: 10.1093/oncolo/oyae146. Oncologist. 2024. PMID: 38906704 Free PMC article. - Real-world data of cardio-oncologic interventions for cardiovascular adverse events with oral oncolytics.
Abboud K, Umoru G, Trachtenberg B, Ajewole V. Abboud K, et al. Cardiooncology. 2024 Apr 9;10(1):22. doi: 10.1186/s40959-024-00221-5. Cardiooncology. 2024. PMID: 38594785 Free PMC article. - Aromatase Inhibitors and Plasma Lipid Changes in Postmenopausal Women with Breast Cancer: A Systematic Review and Meta-Analysis.
Bérczi B, Farkas N, Hegyi P, Tóth B, Csupor D, Németh B, Lukács A, Czumbel LM, Kerémi B, Kiss I, Szabó A, Varga G, Gerber G, Gyöngyi Z. Bérczi B, et al. J Clin Med. 2024 Mar 21;13(6):1818. doi: 10.3390/jcm13061818. J Clin Med. 2024. PMID: 38542042 Free PMC article. Review. - Tamoxifen Dose De-Escalation: An Effective Strategy for Reducing Adverse Effects?
Buijs SM, Koolen SLW, Mathijssen RHJ, Jager A. Buijs SM, et al. Drugs. 2024 Apr;84(4):385-401. doi: 10.1007/s40265-024-02010-x. Epub 2024 Mar 14. Drugs. 2024. PMID: 38480629 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous