Title: Improving outcomeS for Women diagnosed with early breast cancer through adhErence to adjuvant Endocrine Therapy (SWEET)
Funder: Department of Health and Social Care

Abstract: Background There is strong evidence that five years of adjuvant endocrine therapy (AET) substantially reduces risks of recurrence and mortality in estrogen-receptor (ER) positive early breast cancer. Recent guidance recommends extending use beyond five years. However, adherence is sub-optimal: 20% of women show poor adherence at two years and 50% at five years. Poor adherence is strongly associated with increasing risk of recurrence and death, and is related to worse cancer-specific health-related quality-of-life (HRQoL). Our preparatory research reveals reasons for poor adherence include: feeling negative or concerned about taking AET; not understanding its importance; AET-related side-effects; feeling unsupported; and forgetfulness. No effective interventions to support women with AET adherence currently exist. Aim To develop and evaluate an intervention to reduce poor adherence to AET and improve cancer-specific HRQoL and, in the longer-term, reduce recurrence, in women with ER-positive invasive breast cancer. Methods WS1 will iteratively develop a person-centred, evidence-based, theoretically-informed intervention to support AET adherence. We envisage this will be tailored and will include a face-to-face consultation with a trained health professional soon after AET prescription to discuss beliefs, concerns and AET experiences, with introduction of an app/website or workbook providing information, a symptom monitoring tool, and other support mechanisms. A three-month follow-up telephone consultation will address any emerging concerns and communicate continued importance of treatment. Women will also receive regular contact via routine text/email messages. WS2 will use mixed methods to assess the feasibility and acceptability of the intervention and the future randomised controlled trial (RCT). Any final modifications to the intervention will be made. WS3 will deliver a RCT with an internal pilot and process evaluation. 1018 eligible women at medium/high risk of recurrence will be randomised to usual care or intervention+usual care. Adherence, cancer-specific HRQoL, and potential mediators, will be measured at 6, 12 and 18-months post-randomisation. WS4 will assess the cost-effectiveness of the intervention, within trial and longer term, and conduct a budget impact analysis. WS5 will use theory, qualitative research and stakeholder involvement to develop a pathway to impact and inform potential for scale-up within the NHS. If the intervention is effective in reducing poor adherence, WS6 will assess effectiveness in reducing recurrence at five years. PPI will be integral throughout. Timelines for Delivery WS1-5 will be delivered over six years (with WS6, if undertaken, in years 9-10). Intervention development and feasibility testing will be completed within two years; the internal pilot will be completed by month 34. Anticipated Impact and Dissemination More than 11,500 women die from the breast cancer annually in the UK. This programme offers potential to reduce breast cancer recurrences and deaths benefiting patients, the NHS and society. By improving HRQoL it will further significantly benefit many patients. Wider potential can be envisaged in relation to supporting adherence to other anti-cancer oral therapies, and long-term medications, and informing studies looking at new approaches to cancer follow-up. Findings will be disseminated via: presentations, publications, website, social media, stakeholder briefing/events, and PPI engagement. Partnerships with charities and commissioners will enhance implementation and sustainability.

Lay abstract: In 2016, 11,563 women died from breast cancer in the UK. Most would have been prescribed endocrine therapy (ET); sometimes known as hormone therapy, which blocks the effect of oestrogen on breast cancer cells. ET is prescribed as a daily tablet, usually for at least five years. When women stop taking ET prematurely, or don t take it as prescribed (known as &ldquo;poor adherence&rdquo;), they have up to a three times higher chance of the cancer returning and dying from cancer. At least 20% of women have poor adherence after two years and around 50% by five years. Our previous research has identified reasons for poor adherence, including: feeling negative or concerned about ET; not fully understanding its importance; side-effects; feeling unsupported; and forgetfulness. This research programme, supported by a User and Clinical Advisory Groups, will develop and test a support package to help women take ET. It will target women with a higher risk of breast cancer returning. Stage 1: We will work closely with patients and health professionals to develop the support package. We think it will involve an initial appointment with a trained health professional (e.g. nurse) shortly after ET prescription, to discuss the woman s beliefs, concerns and initial experiences of ET. We will develop an App/website/booklet providing information, reminders and other support features. Women will receive a follow-up phone call at three months. Women will also receive regular, tailored, contact using text or email messages, recommending contacting Breast Cancer Care support services or their clinical team if they have any concerns with ET. Stage 2: We will test how the support package can be put into practice, in three different hospitals, and check if it is acceptable to women. Stage 3: If Stage 2 findings are promising, we will then conduct a &ldquo;trial&rdquo; of the support package. Around 1,000 women from 15-20 hospitals will be randomly put into two groups: one group will receive care as usual and the other group will receive care as usual plus the support package. The trial will establish if, after 18 months, the women who receive the additional support package have better ET adherence and quality-of-life than those who do not. Stage 4: We will calculate the costs of the support package to see if it is worth the NHS providing it nationwide. Stage 5: We will investigate how the support package could best be rolled-out across the NHS. Stage 6: If adherence is better after 18 months for women who receive the package, we will see if breast cancer recurrence at 5 years is less common in this group. We will publish our findings, and work with Charities, commissioners and other organisations to ensure results are used to benefit patients.

Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING;7.1 INDIVIDUAL CARE NEEDS
Health categories: CANCER AND NEOPLASMS