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      Adherence to adjuvant endocrine therapy among breast cancer survivors: a systematic review and meta-synthesis of the qualitative literature using grounded theory

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          Abstract

          Purpose

          Numerous studies have examined non-adherence to adjuvant endocrine therapy in women recovering from breast cancer, but none provides a comprehensive theory to explain the challenges of long-term medication taking and resilience needed to continue. The aim of this study was to source, appraise, and synthesize data from existing qualitative studies to develop an in-depth explanatory model of non-adherence and discontinuation of hormonal medication among breast cancer survivors.

          Methods

          A comprehensive search of databases and the literature identified 24 eligible qualitative studies published 2010–2019. Quotations ( n = 801) listed within these papers and the original author interpretations were synthesized using NVivo, and grounded theory methodology.

          Results

          At the beginning, knowledge about adjuvant endocrine therapy, trust in doctors, and worries and expectations, mean agreeing to medication is the only viable option, akin to a Hobson’s choice. Thereafter, women’s ability to deal with medication side-effects, knowledge and support received affect their decision to continue, akin to a horned dilemma where giving up the medication risks cancer recurrence and continuing means reduced contentment. Women stopping medication altogether question treatment necessity, search for normalcy and prioritize quality of life.

          Conclusion

          Shared experiences and understandings were uncovered by examining commonalities in existing publications. The core category explained the difficulties women face with the initial decision to accept long-term endocrine therapy and then the everyday challenges of continuing or deciding to stop treatment early. An educational tool to inform survivors and health professionals about these challenges could potentially improve women’s experience on treatment and in turn their adherence.

          Electronic supplementary material

          The online version of this article (10.1007/s00520-020-05585-9) contains supplementary material, which is available to authorized users.

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          Most cited references26

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          Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials.

          The optimal ways of using aromatase inhibitors or tamoxifen as endocrine treatment for early breast cancer remains uncertain.
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            Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial

            Summary Background For women with oestrogen receptor (ER)-positive early breast cancer, treatment with tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the first 15 years after diagnosis. We aimed to assess the further effects of continuing tamoxifen to 10 years instead of stopping at 5 years. Methods In the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial, 12 894 women with early breast cancer who had completed 5 years of treatment with tamoxifen were randomly allocated to continue tamoxifen to 10 years or stop at 5 years (open control). Allocation (1:1) was by central computer, using minimisation. After entry (between 1996 and 2005), yearly follow-up forms recorded any recurrence, second cancer, hospital admission, or death. We report effects on breast cancer outcomes among the 6846 women with ER-positive disease, and side-effects among all women (with positive, negative, or unknown ER status). Long-term follow-up still continues. This study is registered, number ISRCTN19652633. Findings Among women with ER-positive disease, allocation to continue tamoxifen reduced the risk of breast cancer recurrence (617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls, p=0·002), reduced breast cancer mortality (331 deaths vs 397 deaths, p=0·01), and reduced overall mortality (639 deaths vs 722 deaths, p=0·01). The reductions in adverse breast cancer outcomes appeared to be less extreme before than after year 10 (recurrence rate ratio [RR] 0·90 [95% CI 0·79–1·02] during years 5–9 and 0·75 [0·62–0·90] in later years; breast cancer mortality RR 0·97 [0·79–1·18] during years 5–9 and 0·71 [0·58–0·88] in later years). The cumulative risk of recurrence during years 5–14 was 21·4% for women allocated to continue versus 25·1% for controls; breast cancer mortality during years 5–14 was 12·2% for women allocated to continue versus 15·0% for controls (absolute mortality reduction 2·8%). Treatment allocation seemed to have no effect on breast cancer outcome among 1248 women with ER-negative disease, and an intermediate effect among 4800 women with unknown ER status. Among all 12 894 women, mortality without recurrence from causes other than breast cancer was little affected (691 deaths without recurrence in 6454 women allocated to continue versus 679 deaths in 6440 controls; RR 0·99 [0·89–1·10]; p=0·84). For the incidence (hospitalisation or death) rates of specific diseases, RRs were as follows: pulmonary embolus 1·87 (95% CI 1·13–3·07, p=0·01 [including 0·2% mortality in both treatment groups]), stroke 1·06 (0·83–1·36), ischaemic heart disease 0·76 (0·60–0·95, p=0·02), and endometrial cancer 1·74 (1·30–2·34, p=0·0002). The cumulative risk of endometrial cancer during years 5–14 was 3·1% (mortality 0·4%) for women allocated to continue versus 1·6% (mortality 0·2%) for controls (absolute mortality increase 0·2%). Interpretation For women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10. These results, taken together with results from previous trials of 5 years of tamoxifen treatment versus none, suggest that 10 years of tamoxifen treatment can approximately halve breast cancer mortality during the second decade after diagnosis. Funding Cancer Research UK, UK Medical Research Council, AstraZeneca UK, US Army, EU-Biomed.
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              Patients' beliefs about prescribed medicines and their role in adherence to treatment in chronic physical illness.

              The aim of this cross-sectional study was to quantify patients' personal beliefs about the necessity of their prescribed medication and their concerns about taking it and to assess relations between beliefs and reported adherence among 324 patients from four chronic illness groups (asthma, renal, cardiac, and oncology). The findings revealed considerable variation in reported adherence and beliefs about medicines within and between illness groups. Most patients (89%) believed that their prescribed medication was necessary for maintaining health. However, over a third had strong concerns about their medication based on beliefs about the dangers of dependence or long-term effects. Beliefs about medicines were related to reported adherence: higher necessity scores correlated with higher reported adherence (r=0.21, n=324, p<0.01) and higher concerns correlated with lower reported adherence (r=0.33, n=324, p<0.01). For 17% of the total sample, concerns scores exceeded necessity scores and these patients reported significantly lower adherence rates (t=-4.28, p<0.001). Stepwise multiple linear regression analysis showed that higher reported adherence rates were associated with higher necessity-concerns difference scores (beta=0.35, p<0.001), a diagnosis of asthma (beta= -0.31, p<0.001), a diagnosis of heart disease (beta=0.19, p<0.001), and age (beta=0.22, p<0.001). Gender, educational experience, or the number of prescribed medicines did not predict reported adherence. Medication beliefs were more powerful predictors of reported adherence than the clinical and sociodemographic factors, accounting for 19% of the explained variance in adherence. These data were consistent with the hypothesis that many patients engage in an implicit cost-benefit analysis in which beliefs about the necessity of their medication are weighed against concerns about the potential adverse effects of taking it and that these beliefs are related to medication adherence.
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                Author and article information

                Contributors
                o.k.o.alomeir@pgr.reading.ac.uk
                Journal
                Support Care Cancer
                Support Care Cancer
                Supportive Care in Cancer
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0941-4355
                1433-7339
                29 June 2020
                29 June 2020
                2020
                : 28
                : 11
                : 5075-5084
                Affiliations
                [1 ]GRID grid.9435.b, ISNI 0000 0004 0457 9566, School of Pharmacy, , University of Reading, Whiteknights Campus, ; Reading, UK
                [2 ]GRID grid.9435.b, ISNI 0000 0004 0457 9566, Department of Pharmacy, , University of Reading, ; PO Box 226, Whiteknights, Reading, Berkshire RG6 6AP UK
                Author information
                https://orcid.org/0000-0002-3800-6825
                https://orcid.org/0000-0002-8600-0663
                http://orcid.org/0000-0001-5403-6170
                Article
                5585
                10.1007/s00520-020-05585-9
                7546985
                32601852
                87894f82-0230-4316-b778-4e9ac72b0e61
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 4 February 2020
                : 18 June 2020
                Funding
                Funded by: University of Reading
                Categories
                Review Article
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2020

                Oncology & Radiotherapy
                adherence, antineoplastic agents, hormonal,systematic review,grounded theory,qualitative research,breast neoplasms

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