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Anastrozole-Associated Joint Pain and Other Symptoms in Patients With Breast Cancer

      Abstract

      More than a third of breast cancer patients undergoing aromatase inhibitor (AI) treatment report joint pain. We conducted a longitudinal study to characterize the course of AI-induced joint pain and other symptoms and to identify potential predictors for developing these symptoms. Patients were recruited before AI initiation. The Brief Pain Inventory, M. D. Anderson Symptom Inventory, and a joint-pain questionnaire were administered at baseline and then biweekly for 1 year. Analysis included logistic regression, Cox models, and mixed-effects models. Of 47 patients assessed, 16 (34%) reported joint pain at least once. Median time to first report of joint pain was 7 weeks (range, 1–38). Baseline pain was the only predictor for both incidence of joint pain and time to first event. In the first 6 weeks, emergence of joint pain was associated with increase in general pain, fatigue, disturbed sleep, hot flashes, vaginal dryness, and decreased sexual activity. After week 6, having joint pain was associated with increase in general pain and with persistently high fatigue. Having AI-associated joint pain correlated with increase in or persistence of other symptoms likely related to AI therapy. Further research is needed to validate predictors of AI-associated symptoms.

      Perspective

      We demonstrate for the first time that AI-induced joint pain associates with development of other symptoms and that pretreatment pain level is a potential, measurable predictor of symptom development during treatment. Because baseline pain is easily assessed with a brief questionnaire, it can be applied clinically with minimal patient burden.

      Key words

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      References

        • Basch E.
        The missing voice of patients in drug-safety reporting.
        N Engl J Med. 2010; 362: 865-869
        • Burstein H.J.
        Aromatase inhibitor-associated arthralgia syndrome.
        Breast. 2007; 16: 223-234
        • Cella D.
        • Fallowfield L.
        • Barker P.
        • Cuzick J.
        • Locker G.
        • Howell A.
        Quality of life of postmenopausal women in the ATAC (“Arimidex”, tamoxifen, alone or in combination) trial after completion of 5 years' adjuvant treatment for early breast cancer.
        Breast Cancer Res Treat. 2006; 100: 273-284
        • Cleeland C.S.
        • Mendoza T.R.
        • Wang X.S.
        • Chou C.
        • Harle M.T.
        • Morrissey M.
        • Engstrom M.C.
        Assessing symptom distress in cancer patients: The M.D. Anderson Symptom Inventory.
        Cancer. 2000; 89: 1634-1646
        • Cleeland C.S.
        Measurement of pain by subjective report.
        in: Chapman C.R. Loeser J.D. Advances in Pain Research and Therapy. Raven Press, New York, NY1989: 391-403
        • Colleoni M.
        • Giobbie-Hurder A.
        Benefits and adverse effects of endocrine therapy.
        Ann Oncol. 2010; 21: vii107-vii111
        • Coombes R.C.
        • Hall E.
        • Gibson L.J.
        • Paridaens R.
        • Jassem J.
        • Delozier T.
        • Jones S.E.
        • Alvarez I.
        • Bertelli G.
        • Ortmann O.
        • Coates A.S.
        • Bajetta E.
        • Dodwell D.
        • Coleman R.E.
        • Fallowfield L.J.
        • Mickiewicz E.
        • Andersen J.
        • Lønning P.E.
        • Cocconi G.
        • Stewart A.
        • Stuart N.
        • Snowdon C.F.
        • Carpentieri M.
        • Massimini G.
        • Bliss J.M.
        • van de Velde C.
        A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer.
        N Engl J Med. 2004; 350: 1081-1092
        • Crew K.D.
        • Capodice J.L.
        • Greenlee H.
        • Apollo A.
        • Jacobson J.S.
        • Raptis G.
        • Blozie K.
        • Sierra A.
        • Hershman D.L.
        Pilot study of acupuncture for the treatment of joint symptoms related to adjuvant aromatase inhibitor therapy in postmenopausal breast cancer patients.
        J Cancer Surviv. 2007; 1: 283-291
        • Fontaine C.
        • Meulemans A.
        • Huizing M.
        • Collen C.
        • Kaufman L.
        • De Mey J.
        • Bourgain C.
        • Verfaillie G.
        • Lamote J.
        • Sacre R.
        • Schallier D.
        • Neyns B.
        • Vermorken J.
        • De Greve J.
        Tolerance of adjuvant letrozole outside of clinical trials.
        Breast. 2008; 17: 376-381
        • Fransen J.
        • Stucki G.
        • Twisk J.
        • Chamot A.M.
        • Gerster J.C.
        • Langenegger T.
        • Seitz M.
        • Michel B.A.
        Effectiveness of a measurement feedback system on outcome in rheumatoid arthritis: A controlled clinical trial.
        Ann Rheum Dis. 2003; 62: 624-629
        • Henry N.L.
        • Azzouz F.
        • Desta Z.
        • Li L.
        • Nguyen A.T.
        • Lemler S.
        • Hayden J.
        • Tarpinian K.
        • Yakim E.
        • Flockhart D.A.
        • Stearns V.
        • Hayes D.F.
        • Storniolo A.M.
        Predictors of aromatase inhibitor discontinuation as a result of treatment-emergent symptoms in early-stage breast cancer.
        J Clin Oncol. 2012; 30: 936-942
        • Henry N.L.
        • Giles J.T.
        • Ang D.
        • Mohan M.
        • Dadabhoy D.
        • Robarge J.
        • Hayden J.
        • Lemler S.
        • Shahverdi K.
        • Powers P.
        • Li L.
        • Flockhart D.
        • Stearns V.
        • Hayes D.F.
        • Storniolo A.M.
        • Clauw D.J.
        Prospective characterization of musculoskeletal symptoms in early stage breast cancer patients treated with aromatase inhibitors.
        Breast Cancer Res Treat. 2008; 111: 365-372
        • Howell A.
        • Cuzick J.
        • Baum M.
        • Buzdar A.
        • Dowsett M.
        • Forbes J.F.
        • Hoctin-Boes G.
        • Houghton J.
        • Locker G.Y.
        • Tobias J.S.
        Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer.
        Lancet. 2005; 365: 60-62
        • Kapstad H.
        • Rokne B.
        • Stavem K.
        Psychometric properties of the Brief Pain Inventory among patients with osteoarthritis undergoing total hip replacement surgery.
        Health Qual Life Outcomes. 2010; 8: 148
        • Mao J.J.
        • Stricker C.
        • Bruner D.
        • Xie S.
        • Bowman M.A.
        • Farrar J.T.
        • Greene B.T.
        • DeMichele A.
        Patterns and risk factors associated with aromatase inhibitor-related arthralgia among breast cancer survivors.
        Cancer. 2009; 115: 3631-3639
        • Mourits M.J.
        • de Vries E.G.
        • Willemse P.H.
        • ten Hoor K.A.
        • Hollema H.
        • van der Zee A.G.
        Tamoxifen treatment and gynecologic side effects: A review.
        Obstet Gynecol. 2001; 97: 855-866
        • Muslimani A.A.
        • Spiro T.P.
        • Chaudhry A.A.
        • Taylor H.C.
        • Jaiyesimi I.
        • Daw H.A.
        Aromatase inhibitor-related musculoskeletal symptoms: Is preventing osteoporosis the key to eliminating these symptoms?.
        Clin Breast Cancer. 2009; 9: 34-38
        • Presant C.A.
        • Bosserman L.
        • Young T.
        • Vakil M.
        • Horns R.
        • Upadhyaya G.
        • Ebrahimi B.
        • Yeon C.
        • Howard F.
        Aromatase inhibitor-associated arthralgia and/or bone pain: Frequency and characterization in non-clinical trial patients.
        Clin Breast Cancer. 2007; 7: 775-778
        • Sestak I.
        • Cuzick J.
        • Sapunar F.
        • Eastell R.
        • Forbes J.F.
        • Bianco A.R.
        • Buzdar A.U.
        Risk factors for joint symptoms in patients enrolled in the ATAC trial: A retrospective, exploratory analysis.
        Lancet Oncol. 2008; 9: 866-872
        • Thürlimann B.
        • Keshaviah A.
        • Coates A.S.
        • Mouridsen H.
        • Mauriac L.
        • Forbes J.F.
        • Paridaens R.
        • Castiglione-Gertsch M.
        • Gelber R.D.
        • Rabaglio M.
        • Smith I.
        • Wardley A.
        • Price K.N.
        • Goldhirsch A.
        A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer.
        N Engl J Med. 2005; 353: 2747-2757