Abstract
Purpose
The most frequent adverse effects of aromatase inhibitors (AI) are arthralgia and bone loss induction. These reduce the quality of life of patients and their adherence to the treatment. This study evaluates the early AI cessation caused by AI intolerance, and the evolution of joint pain and health-related quality of life (HRQoL) during AI treatment until 1-year after AI completion.
Methods
Data of 910 women diagnosed with early breast cancer and candidates for AI were recruited in B-ABLE cohort. AI discontinuation was analyzed by survival analysis, including Kaplan–Meier estimation and Cox regression. Patients were distributed in three groups of the study according to previous tamoxifen (TAM) exposure and length of AI treatment: TAM-2yAI, TAM-3yAI, and 5yAI. Evolution of joint pain and HRQoL in osteoporosis was evaluated using Visual Analog Scale (VAS) and ECOS-16 tests, respectively, from baseline to 1-year after AI completion through repeated-measures ANOVA.
Results
Risk of AI discontinuation was increased in patients previously exposed to tamoxifen compared to non-exposed (adjusted HR 5.30 [95% CI 2.23 to 12.57]). VAS and ECOS-16 scores of TAM-2yAI and TAM-3yAI groups increased during AI treatment, mainly during the first 3–12 months. After 1-year from AI completion, values tend to decrease to baseline levels. In 5yAI group, VAS and ECOS-16 levels increased at three months, and VAS remained significantly higher at 1-year post-treatment.
Conclusions
AI therapy increased joint pain and reduced HRQoL, mainly during the first year of treatment. Patients previously treated with tamoxifen experienced greater pain when they switched to AI therapy and had an excess risk of discontinuation during the first 12 months.
Trial registration
ClinicalTrials.gov: NCT03811509. Registered 28 January 2018-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03811509.
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References
Burstein HJ, Lacchetti C, Anderson H, Buchholz TA, Davidson NE, Gelmon KA, Giordano SH, Hudis CA, Solky AJ, Stearns V, Winer EP, Griggs JJ (2018) Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: ASCO clinical practice guideline focused update. J Clin Oncol. https://doi.org/10.1200/JCO.18.01160
Cuzick J, Sestak I, Baum M, Buzdar A, Howell A, Dowsett M, Forbes JF, Investigators AL (2010) Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol 11(12):1135–1141. https://doi.org/10.1016/S1470-2045(10)70257-6
Regan MM, Neven P, Giobbie-Hurder A, Goldhirsch A, Ejlertsen B, Mauriac L, Forbes JF, Smith I, Lang I, Wardley A, Rabaglio M, Price KN, Gelber RD, Coates AS, Thurlimann B, Group BIGC, International Breast Cancer Study G (2011) 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 Oncol 12(12):1101–1108. https://doi.org/10.1016/S1470-2045(11)70270-4
Kadakia KC, Snyder CF, Kidwell KM, Seewald NJ, Flockhart DA, Skaar TC, Desta Z, Rae JM, Otte JL, Carpenter JS, Storniolo AM, Hayes DF, Stearns V, Henry NL (2016) Patient-reported outcomes and early discontinuation in aromatase inhibitor-treated postmenopausal women with early stage breast cancer. Oncologist 21(5):539–546. https://doi.org/10.1634/theoncologist.2015-0349
Eastell R, Adams JE, Coleman RE, Howell A, Hannon RA, Cuzick J, Mackey JR, Beckmann MW, Clack G (2008) Effect of anastrozole on bone mineral density: 5-year results from the anastrozole, tamoxifen, alone or in combination trial 18233230. J Clin Oncol 26(7):1051–1057. https://doi.org/10.1200/JCO.2007.11.0726
Laroche F, Coste J, Medkour T, Cottu PH, Pierga JY, Lotz JP, Beerblock K, Tournigand C, Decleves X, de Cremoux P, Bouhassira D, Perrot S (2014) Classification of and risk factors for estrogen deprivation pain syndromes related to aromatase inhibitor treatments in women with breast cancer: a prospective multicenter cohort study. J Pain 15(3):293–303. https://doi.org/10.1016/j.jpain.2013.11.004
Pineda-Moncusi M, Servitja S, Casamayor G, Cos ML, Rial A, Rodriguez-Morera J, Tusquets I, Diez-Perez A, Garcia-Giralt N, Nogues X (2018) Bone health evaluation one year after aromatase inhibitors completion. Bone 117:54–59. https://doi.org/10.1016/j.bone.2018.09.010
Niravath P (2013) Aromatase inhibitor-induced arthralgia: a review. Ann Oncol 24(6):1443–1449. https://doi.org/10.1093/annonc/mdt037
Goldvaser H, Barnes TA, Seruga B, Cescon DW, Ocana A, Ribnikar D, Amir E (2018) Toxicity of extended adjuvant therapy with aromatase inhibitors in early breast cancer: a systematic review and meta-analysis. J Natl Cancer Inst. https://doi.org/10.1093/jnci/djx141
Rizzoli R (2018) Postmenopausal osteoporosis: assessment and management. Best Pract Res Clin Endocrinol Metab 32(5):739–757. https://doi.org/10.1016/j.beem.2018.09.005
Ferreira-Valente MA, Pais-Ribeiro JL, Jensen MP (2011) Validity of four pain intensity rating scales. Pain 152(10):2399–2404. https://doi.org/10.1016/j.pain.2011.07.005
Badia X, Diez-Perez A, Lahoz R, Lizan L, Nogues X, Iborra J (2004) The ECOS-16 questionnaire for the evaluation of health related quality of life in post-menopausal women with osteoporosis. Health Qual Life Outcomes 2:41. https://doi.org/10.1186/1477-7525-2-41
Hawker GA, Mian S, Kendzerska T, French M (2011) Measures of adult pain: visual analog scale for pain (VAS Pain), numeric rating scale for pain (NRS Pain), McGill pain questionnaire (MPQ), short-form McGill pain questionnaire (SF-MPQ), chronic pain grade scale (CPGS), short form-36 bodily pain scale (SF-36 BPS), and measure of intermittent and constant osteoarthritis pain (ICOAP). Arthritis Care Res (Hoboken) 63(Suppl 11):S240–252. https://doi.org/10.1002/acr.20543
Prieto-Alhambra D, Javaid MK, Servitja S, Arden NK, Martinez-Garcia M, Diez-Perez A, Albanell J, Tusquets I, Nogues X (2011) Vitamin D threshold to prevent aromatase inhibitor-induced arthralgia: a prospective cohort study. Breast Cancer Res Treat 125(3):869–878. https://doi.org/10.1007/s10549-010-1075-9
Garcia-Giralt N, Rodriguez-Sanz M, Prieto-Alhambra D, Servitja S, Torres-Del Pliego E, Balcells S, Albanell J, Grinberg D, Diez-Perez A, Tusquets I, Nogues X (2013) Genetic determinants of aromatase inhibitor-related arthralgia: the B-ABLE cohort study. Breast Cancer Res Treat 140(2):385–395. https://doi.org/10.1007/s10549-013-2638-3
ClinicalTrials.gov (2019) Study for improving life quality in breast cancer women treated with aromatase inhibitors: cohort B-ABLE. Parc de Salut Mar, Instituto de Salud Carlos III, Hospital del Mar, Barcelona
Rodriguez-Sanz M, Prieto-Alhambra D, Servitja S, Garcia-Giralt N, Garrigos L, Rodriguez-Morera J, Albanell J, Martinez-Garcia M, Gonzalez I, Diez-Perez A, Tusquets I, Nogues X (2016) AI-related BMD variation in actual practice conditions: a prospective cohort study. Endocr Relat Cancer 23(4):303–312. https://doi.org/10.1530/ERC-16-0025
Servitja S, Nogues X, Prieto-Alhambra D, Martinez-Garcia M, Garrigos L, Pena MJ, de Ramon M, Diez-Perez A, Albanell J, Tusquets I (2012) Bone health in a prospective cohort of postmenopausal women receiving aromatase inhibitors for early breast cancer. Breast 21(1):95–101. https://doi.org/10.1016/j.breast.2011.09.001
Winer EP, Hudis C, Burstein HJ, Wolff AC, Pritchard KI, Ingle JN, Chlebowski RT, Gelber R, Edge SB, Gralow J, Cobleigh MA, Mamounas EP, Goldstein LJ, Whelan TJ, Powles TJ, Bryant J, Perkins C, Perotti J, Braun S, Langer AS, Browman GP, Somerfield MR (2005) American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer: status report 2004. J Clin Oncol 23(3):619–629. https://doi.org/10.1200/JCO.2005.09.121
Henry NL, Azzouz F, Desta Z, Li L, Nguyen AT, Lemler S, Hayden J, Tarpinian K, Yakim E, Flockhart DA, Stearns V, Hayes DF, Storniolo AM (2012) Predictors of aromatase inhibitor discontinuation as a result of treatment-emergent symptoms in early-stage breast cancer. J Clin Oncol 30(9):936–942. https://doi.org/10.1200/JCO.2011.38.0261
Santa-Maria CA, Bardia A, Blackford AL, Snyder C, Connolly RM, Fetting JH, Hayes DF, Jeter SC, Miller RS, Nguyen A, Quinlan K, Rosner GL, Slater S, Storniolo AM, Wolff AC, Zorzi J, Henry NL, Stearns V (2018) A phase II study evaluating the efficacy of zoledronic acid in prevention of aromatase inhibitor-associated musculoskeletal symptoms: the ZAP trial. Breast Cancer Res Treat. https://doi.org/10.1007/s10549-018-4811-1
Basch E, Jia X, Heller G, Barz A, Sit L, Fruscione M, Appawu M, Iasonos A, Atkinson T, Goldfarb S, Culkin A, Kris MG, Schrag D (2009) Adverse symptom event reporting by patients vs clinicians: relationships with clinical outcomes. J Natl Cancer Inst 101(23):1624–1632. https://doi.org/10.1093/jnci/djp386
Wang J, Tang X, Shen Y, Shang G, Fang L, Wang R, Xu Y (2015) The correlations between health-related quality of life changes and pain and anxiety in orthodontic patients in the initial stage of treatment. Biomed Res Int 2015:725913. https://doi.org/10.1155/2015/725913
Kawai K, Kawai AT, Wollan P, Yawn BP (2017) Adverse impacts of chronic pain on health-related quality of life, work productivity, depression and anxiety in a community-based study. Fam Pract 34(6):656–661. https://doi.org/10.1093/fampra/cmx034
Acknowledgements
We would like to thank Elaine M. Lilly, PhD, for providing language assistance, helpful advice, and critical reading of the manuscript.
Funding
This work was funded by the Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES) [Grant Number CB16/10/00245]; FIS Project from Instituto de Salud Carlos III (ISCIII), Ministerio de Ciencia e Innovación [Grant Number PI16/00818 and PI17/01875], and FEDER funds.
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The ethics committee of Parc de Salut Mar (2016/6803/I) approved the study protocol, which was carried out in accordance with the 1964 Declaration of Helsinki and its later amendments.
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Informed consent was obtained from all individual participants included in the study after they had read the study information sheet and any questions had been answered. The privacy rights of human subjects are carefully protected in our institution.
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Pineda-Moncusí, M., Servitja, S., Tusquets, I. et al. Assessment of early therapy discontinuation and health-related quality of life in breast cancer patients treated with aromatase inhibitors: B-ABLE cohort study. Breast Cancer Res Treat 177, 53–60 (2019). https://doi.org/10.1007/s10549-019-05289-7
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DOI: https://doi.org/10.1007/s10549-019-05289-7