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      Aromatase inhibitors are associated with a higher fracture risk than tamoxifen: a systematic review and meta-analysis

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          Abstract

          <div class="section"> <a class="named-anchor" id="section1-1759720X18759291"> <!-- named anchor --> </a> <h5 class="section-title" id="d13290031e147">Background:</h5> <p id="d13290031e149">In this paper, our aim was to systematically evaluate published evidence of bone fracture risk associated with tamoxifen and aromatase inhibitors in women aged 65 and under, and diagnosed with nonmetastatic breast cancer. </p> </div><div class="section"> <a class="named-anchor" id="section2-1759720X18759291"> <!-- named anchor --> </a> <h5 class="section-title" id="d13290031e152">Methods:</h5> <p id="d13290031e154">We comprehensively searched MEDLINE, EMBASE and CINAHL databases from January 1997 through May 2015, and reference lists of the selected articles to identify English-language randomized controlled trials and cohort studies of fracture risk. Two independent reviewers screened articles and assessed methodological quality using Risk of Bias assessment for randomized controlled trials and the Newcastle–Ottawa Scale for cohort studies. Fracture risk was estimated as pooled risk ratios using a random-effects model and inverse variance method. </p> </div><div class="section"> <a class="named-anchor" id="section3-1759720X18759291"> <!-- named anchor --> </a> <h5 class="section-title" id="d13290031e157">Results:</h5> <p id="d13290031e159">Of 1926 identified articles, 21 independent studies fulfilled our selection criteria. Similar fracture risk was observed in women treated and not treated with tamoxifen [pooled risk ratio (RR) 0.95; 95% confidence interval (CI) 0.84–1.07]. A 35% (95% CI 1.21–1.51) higher fracture risk was observed in the aromatase inhibitor group compared with the tamoxifen group. A 17% (95% CI 1.07–1.28) higher fracture risk was observed in the aromatase inhibitor group than the no aromatase inhibitor group. Compared with the tamoxifen group, aromatase inhibitor-associated fracture risk increased by 33% (pooled RR 1.33; 95% CI 1.21–1.47) during the tamoxifen/aromatase inhibitor treatment period, but did not increase (pooled RR 0.99; 95% CI 0.72–1.37) during the post-tamoxifen/aromatase inhibitor treatment period. </p> </div><div class="section"> <a class="named-anchor" id="section4-1759720X18759291"> <!-- named anchor --> </a> <h5 class="section-title" id="d13290031e162">Conclusions:</h5> <p id="d13290031e164">Fracture risk is significantly higher in women treated with aromatase inhibitors, especially during the treatment period. Tamoxifen is not associated with lower fracture risk while tamoxifen could potentially preserve bone mass. Better osteoporosis management programs, especially during the treatment period, are needed for this group of women. </p> </div>

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          2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary.

          Alexandra Papaioannou, Suzanne Morin, Angela Cheung … (2010)
          Article 0 comments Cited 295 times – based on 0 reviews     Review now
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            A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer.

            Beat Thürlimann, Aparna Keshaviah, Alan S Coates … (2005)
            The aromatase inhibitor letrozole is a more effective treatment for metastatic breast cancer and more effective in the neoadjuvant setting than tamoxifen. We compared letrozole with tamoxifen as adjuvant treatment for steroid-hormone-receptor-positive breast cancer in postmenopausal women. The Breast International Group (BIG) 1-98 study is a randomized, phase 3, double-blind trial that compared five years of treatment with various adjuvant endocrine therapy regimens in postmenopausal women with hormone-receptor-positive breast cancer: letrozole, letrozole followed by tamoxifen, tamoxifen, and tamoxifen followed by letrozole. This analysis compares the two groups assigned to receive letrozole initially with the two groups assigned to receive tamoxifen initially; events and follow-up in the sequential-treatment groups were included up to the time that treatments were switched. A total of 8010 women with data that could be assessed were enrolled, 4003 in the letrozole group and 4007 in the tamoxifen group. After a median follow-up of 25.8 months, 351 events had occurred in the letrozole group and 428 events in the tamoxifen group, with five-year disease-free survival estimates of 84.0 percent and 81.4 percent, respectively. As compared with tamoxifen, letrozole significantly reduced the risk of an event ending a period of disease-free survival (hazard ratio, 0.81; 95 percent confidence interval, 0.70 to 0.93; P=0.003), especially the risk of distant recurrence (hazard ratio, 0.73; 95 percent confidence interval, 0.60 to 0.88; P=0.001). Thromboembolism, endometrial cancer, and vaginal bleeding were more common in the tamoxifen group. Women given letrozole had a higher incidence of skeletal and cardiac events and of hypercholesterolemia. In postmenopausal women with endocrine-responsive breast cancer, adjuvant treatment with letrozole, as compared with tamoxifen, reduced the risk of recurrent disease, especially at distant sites. (ClinicalTrials.gov number, NCT00004205.) Copyright 2005 Massachusetts Medical Society.
            Article 0 comments Cited 268 times – based on 0 reviews     Review now
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              Endocrine therapy plus zoledronic acid in premenopausal breast cancer.

              Michael Gnant, Brigitte Mlineritsch, Walter Schippinger … (2009)
              Ovarian suppression plus tamoxifen is a standard adjuvant treatment in premenopausal women with endocrine-responsive breast cancer. Aromatase inhibitors are superior to tamoxifen in postmenopausal patients, and preclinical data suggest that zoledronic acid has antitumor properties. We examined the effect of adding zoledronic acid to a combination of either goserelin and tamoxifen or goserelin and anastrozole in premenopausal women with endocrine-responsive early breast cancer. We randomly assigned 1803 patients to receive goserelin (3.6 mg given subcutaneously every 28 days) plus tamoxifen (20 mg per day given orally) or anastrozole (1 mg per day given orally) with or without zoledronic acid (4 mg given intravenously every 6 months) for 3 years. The primary end point was disease-free survival; recurrence-free survival and overall survival were secondary end points. After a median follow-up of 47.8 months, 137 events had occurred, with disease-free survival rates of 92.8% in the tamoxifen group, 92.0% in the anastrozole group, 90.8% in the group that received endocrine therapy alone, and 94.0% in the group that received endocrine therapy with zoledronic acid. There was no significant difference in disease-free survival between the anastrozole and tamoxifen groups (hazard ratio for disease progression in the anastrozole group, 1.10; 95% confidence interval [CI], 0.78 to 1.53; P=0.59). The addition of zoledronic acid to endocrine therapy, as compared with endocrine therapy without zoledronic acid, resulted in an absolute reduction of 3.2 percentage points and a relative reduction of 36% in the risk of disease progression (hazard ratio, 0.64; 95% CI, 0.46 to 0.91; P=0.01); the addition of zoledronic acid did not significantly reduce the risk of death (hazard ratio, 0.60; 95% CI, 0.32 to 1.11; P=0.11). Adverse events were consistent with known drug-safety profiles. The addition of zoledronic acid to adjuvant endocrine therapy improves disease-free survival in premenopausal patients with estrogen-responsive early breast cancer. (ClinicalTrials.gov number, NCT00295646.) 2009 Massachusetts Medical Society
              Article 0 comments Cited 196 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Title: Therapeutic Advances in Musculoskeletal Disease
                Abbreviated Title: Therapeutic Advances in Musculoskeletal
                Publisher: SAGE Publications
                ISSN (Print): 1759-720X
                ISSN (Electronic): 1759-7218
                Publication date Created: March 22 2018
                Publication date Created: April 2018
                Publication date (Electronic): March 22 2018
                Publication date (Print): April 2018
                Volume: 10
                Issue: 4
                Pages: 71-90
                Affiliations
                [1 ]Department of Family Practice, University of British Columbia, 3rd floor David Strangway Building, 5950 University Boulevard Building, Vancouver, BC V6T 1Z3, Canada
                [2 ]Cancer Control Research Department, BC Cancer Research Centre, BC, Canada School of Population and Public Health, University of British Columbia, BC, Canada
                [3 ]Faculty of Pharmaceutical Science, University of British Columbia, Vancouver, BC, Canada
                [4 ]Department of Family Practice, University of British Columbia, Vancouver, BC, Canada
                Article
                DOI: 10.1177/1759720X18759291
                PMC ID: 5871065
                PubMed ID: 29619093
                SO-VID: 24fcd89f-084f-4207-93a4-fd01e7d63866
                Copyright © © 2018
                License:

                http://journals.sagepub.com/page/policies/text-and-data-mining-license

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