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Background: Multi-parameter tumor gene expression assays (MPAs) are used to estimate individual patient risk and guide chemotherapy use in hormone-sensitive, HER2-negative early breast cancer. The TAILORx trial supports MPA use in a node-negative population. Evidence for MPA use in postmenopausal node-positive breast cancer has been provided by the RxPONDER trial interim analysis but this relies on the absence of superiority in an analysis where >50% of events were unrelated to breast cancer. There is much uncertainty about MPA use for premenopausal patients. OPTIMA (Optimal Personalised Treatment of early breast cancer usIng Multi-parameter Analysis) (ISRCTN42400492) is a prospective international randomized controlled trial designed to validate MPAs as predictors of chemotherapy sensitivity in a largely node-positive breast cancer population. Methods: OPTIMA is a partially blinded study with an adaptive two-stage design. The trial recruits women and men age 40 or older with resected ER-positive, HER2-negative invasive breast cancer and up to 9 involved axillary lymph nodes. Randomization is to standard management (chemotherapy and endocrine therapy) or to MPA-directed treatment using the Prosigna (PAM50) test. Those with a Prosigna tumor Score (ROR_PT) >60 receive standard management whilst those with a low score (≤60) tumor are treated with endocrine therapy alone. Endocrine therapy for pre-menopausal women includes ovarian suppression for all participants unless they experience a chemotherapy-induced menopause. Adjuvant abemaciclib is permitted. The trial will be analyzed for (1) non-inferiority of recurrence according to randomization and (2) cost-effectiveness. The key secondary outcome is non-inferiority of recurrence for patients with low ROR_PT score tumors. The efficacy analyses will be performed Per Protocol using Invasive Breast Cancer Free Survival (IBCFS) as the primary outcome measure to limit the risk of a false non-inferiority conclusion. Recruitment of 4500 patients over 8 years will permit demonstration of up to 3% non-inferiority of test-directed treatment with at least 83% power, assuming 5-year IBCFS is 87% with standard management. An integrated qualitative recruitment study addresses challenges to consent and recruitment, building on experience from the feasibility study which found that a multidisciplinary approach is important for recruitment success. OPTIMA is strongly supported by a patient group which has helped design all patient documents and which is represented on the TMG. Results: The OPTIMA main trial opened in January 2017 and has continued to recruit throughout the COVID-19 pandemic. Overall recruitment as of 1 July 2022 was 2814 (2593 from UK, 221 from Norway). Patient characteristics are well balanced between the trial arms. Currently 95% of randomized participants are eligible for inclusion in the PP analysis. 66% of the MPA-directed arm participants have been allocated to endocrine therapy only. The test failure rate is < 1%. Conclusion: OPTIMA will provide robust unbiased evidence on test-directed chemotherapy safety for both postmenopausal and premenopausal women with 1-3 involved nodes as well as for patients with 4-9 involved nodes and for patients treated with abemaciclib. Funding: OPTIMA is funded by the UK NIHR HTA Programme (10/34/501) and in Norway by KLINBEFORSK and the Norwegian Cancer Society. Views expressed are those of the authors and not those of the HTA Programme, NIHR, NHS or the Department of Health. Trial Inquiries: OPTIMA@warwick.ac.uk Patient characteristics Citation Format: Robert Stein, Andreas Makris, Iain Macpherson, Luke Hughes-Davies, Andrea Marshall, Georgina Dotchin, David A. Cameron, Belinda E. Kiely, Caroline Wilson, Anne Armstrong, Helena M. Earl, Christopher J. Poole, Janice Tsang, Bjørn Naume, Daniel Rea, Hege Ohnstad, Peter S. Hall, Stuart A. McIntosh, Bethany Shinkins, Christopher McCabe, Adrienne Morgan, John MS Bartlett, Janet A. Dunn. OPTIMA, a prospective randomized trial to validate the clinical utility and cost-effectiveness of gene expression test-directed chemotherapy decisions in high clinical risk early breast cancer. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-32-01.

Background: Multi-parameter tumour gene expression assays (MPAs) are widely used to estimate individual patient risk and to guide chemotherapy use in hormone-sensitive, HER2-negative early breast cancer. The TAILORx trial supports MPA use in a node-negative population. Evidence in node-positive breast cancer is limited. OPTIMA (Optimal Personalised Treatment of early breast cancer usIng Multi-parameter Analysis) (ISRCTN42400492) is a prospective international randomised controlled trial (RCT) designed to validate MPA’s as predictors of chemotherapy sensitivity in a largely node-positive breast cancer population. Methods: OPTIMA is a partially blinded study with an adaptive two-stage design. The main eligibility criteria are women and men age 40 or older with resected ER-positive, HER2-negative invasive breast cancer and up to 9 involved axillary lymph nodes. Randomisation is to standard management (chemotherapy and endocrine therapy) or to MPA-directed treatment using the Prosigna (PAM50) test. Those with a Prosigna tumour Score (ROR_PT) >60 receive standard management whilst those with a low score (≤60) are treated with endocrine therapy alone. Endocrine therapy for pre-menopausal women includes ovarian suppression. Prosigna tests are currently performed only for participants randomised to MPA-directed treatment. More than 1 tumour may be tested if participants have multi-focal tumours with discordant features and/or are considered clinically significant. The co-primary outcomes are: (1) Invasive Disease Free Survival (IDFS) and (2) cost-effectiveness. Secondary outcomes include IDFS in patients with low-score tumours and quality of life. Recruitment of 4500 patients over 5 years will permit demonstration of 3% non-inferiority of test-directed treatment, assuming 5-year IDFS of 85% with standard management. An integrated qualitative recruitment study addresses challenges to consent and recruitment, building on experience from the feasibility study which found that a multidisciplinary approach is important for recruitment success. Results: The OPTIMA main trial opened in January 2017. Overall recruitment as of 1 July 2019 was 1123 (1100 from UK, 13 from Norway); 91% had axillary node macro-metastases. Median time from consent to treatment allocation was 12 days (interquartile range 10-14 days). The withdrawal rate from trial treatment is 3%; 50% of these continue with follow up. Prosigna tests have been performed on 608 tumours for 549 participants; 59% were luminal A, 38% were luminal B and 3% non-luminal (6 patients with non-luminal tumours [1% overall] were ineligible on receptor retesting). Of the 53 (10%) participants with >1 tumour tested, 3 (6%) had discordant scores only, 7 (13%) had discordant subtypes only and 8 (15%) had both discordant scores and subtypes. Two thirds of the MPA-directed arm participants have been allocated to endocrine therapy only. The test failure rate is Conclusion: OPTIMA is one of two large scale prospective trials validating the use of test-guided chemotherapy decisions in node-positive early breast cancer. It is expected to have a global impact on breast cancer treatment. Funding: OPTIMA is funded by the UK NIHR HTA Programme (10/34/501). Views expressed are those of the authors and not those of the HTA Programme, NIHR, NHS or the Department of Health. Trial Inquiries: OPTIMA@warwick.ac.uk Citation Format: Robert C Stein, Andrea Marshall, Andreas Makris, Luke Hughes-Davies, Iain R MacPherson, Carmel Conefrey, Leila Rooshenas, Sarah E Pinder, Abeer M Shaaban, Bjørn Naume, David A Cameron, Daniel W Rea, Helena M Earl, Christopher J Poole, Peter S Hall, Georgina Dotchin, Stuart A McIntosh, Victoria Harmer, Adrienne Morgan, Bethany Shinkins, Nigel Stallard, Christopher McCabe, Jenny L Donovan, John MS Bartlett, Janet A Dunn. OPTIMA: A prospective randomized trial to validate the clinical utility and cost-effectiveness of gene expression test-directed chemotherapy decisions in mostly node-positive early breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT3-17-01.

Background:Multi-parameter tumour gene expression assays (MPAs) are widely used to estimate individual patient residual risk and to guide chemotherapy use in hormone-sensitive, HER2-negative early breast cancer. The TAILORx trial supports MPA use in a node-negative population. Evidence for MPA use in node-positive breast cancer is limited. OPTIMA (Optimal Personalised Treatment of early breast cancer usIng Multi-parameter Analysis) (ISRCTN42400492) aims to validate MPAs as predictors of chemotherapy sensitivity in a largely node-positive breast cancer population where prospective RCT (Randomised Controlled Trial) evidence is lacking. Methods: OPTIMA is a partially blinded multi-center RCT with an adaptive two-stage design. The main eligibility criteria are women and men age 40 or older with resected ER-positive, HER2-negative invasive breast cancer and up to 9 involved axillary lymph nodes. Randomisation is to standard management (chemotherapy and endocrine therapy) or to MPA-directed treatment using the Prosigna (PAM50) test. Those with a Prosigna tumour score (ROR_PT) >60 receive standard management whilst those with a low score (≤60) are treated with endocrine therapy alone. Endocrine therapy for pre-menopausal women includes ovarian suppression. The co-primary outcomes are (1) Invasive Disease Free Survival (IDFS) and (2) cost-effectiveness of test-directed treatment. Secondary outcomes include IDFS in patients with low-score tumours and quality of life. An integrated qualitative recruitment study addresses challenges to consent and recruitment and will build on experience from the feasibility study that a multidisciplinary approach at sites is important for recruitment success. Tumour blocks will be banked to allow evaluation of additional MPA technologies. Recruitment of 4500 patients over 5 years will permit demonstration of 3% non-inferiority of test-directed treatment, assuming 5-year IDFS of 85% with standard management, equivalent to a HR of 1.22. Inclusion of patients from the feasibility study will increase the power to test for non-inferiority. Results: The OPTIMA main trial opened in January 2017. Overall recruitment (including the feasibility study) will reach 1000 in August 2018. Recruitment in Norway will commence in July 2018. Characteristics of the OPTIMA main participants recruited to 31st May 2018 are shown in the table. Main study patient characteristicsCharacteristic %Median age in years (range)57 (40-80) Menopause statusPre34 Post66 Male1Tumour size=30mm42Node statuspN04 pN1mi(sn)7 pN1(sn)20 pN155 pN214Historic grade16 258 336 Conclusion: OPTIMA is one of two large scale prospective trials validating the use of test-guided chemotherapy decisions in node-positive early breast cancer. It is expected to have a global impact on breast cancer treatment. Experience from the preliminary study and close engagement with centres will aid trial success. Funding: OPTIMA is funded by the UK NIHR HTA Programme (10/34/501). Views expressed are those of the authors and not those of the HTA Programme, NIHR, NHS or the DoH. Citation Format: Stein RC, Hughes-Davies L, Makris A, Macpherson IR, Conefrey C, Rooshenas L, Pinder SE, Thomas J, Hall PS, Cameron DA, Earl HM, Naume B, Poole CJ, Rea DW, MacIntosh SA, Harmer V, Morgan A, Hulme C, McCabe C, Stallard N, Higgins H, Donovan JL, Bartlett JM, Marshall A, Dunn JA. OPTIMA: A prospective randomized trial to validate the clinical utility and cost-effectiveness of gene expression test-directed chemotherapy decisions in high clinical risk early breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT1-05-02.

Purpose The aim of this study was to identify the most appropriate measure of quality of life (QoL) for patients living with and beyond cancer. Methods One hundred eighty-two people attending cancer clinics in Central London at various stages post-treatment, completed a series of QoL measures: FACT-G, EORTC QLQ-C30 , IOCv2 (positive and negative subscales) and WEMWBS, a wellbeing measure. These measures were chosen as the commonest measures used in previous research. Correlation tests were used to assess the association between scales. Participants were also asked about pertinence and ease of completion. Results There was a significant positive correlation between the four domain scores of the two health-related QoL measures (.32 ≤ r ≤ .72, P < .001), and a significant large negative correlation between these and the negative IOCv2 subscale scores (− .39 ≤ r ≤ − .63, P < .001). There was a significant moderate positive correlation between positive IOCv2 subscale and WEMWBS scores (r = .35, P < .001). However, neither the FACT-G nor the EORTC showed any significant correlation with the positive IOCv2 subscale. Participants rated all measures similarly with regards to pertinence and ease of use. Conclusion There was little to choose between FACT-G, EORTC, and the negative IOC scales, any of which may be used to measure QoL. However, the two IOCv2 subscales capture unique aspects of QoL compared to the other measures. The IOCv2 can be used to identify those cancer survivors who would benefit from interventions to improve their QoL and to target specific needs thereby providing more holistic and personalised care beyond cancer treatment.

Introduction Health care professionals who identify as members of underrepresented and racial minority groups may experience bias from patients and patient families. These occurrences disrupt the educational and therapeutic environments, distress the targeted individuals and allies, and create potential legal liability. Yet there are few educational opportunities for individuals to brainstorm and implement strategies for responding professionally during such instances. Methods Presented first as a grand rounds, then an invited workshop, and finally an invited series, this educational activity was developed in a stepwise manner over the course of a year. Each format was sequentially modified based on feedback from participants—more than 200 physicians and other health care professionals—using evaluation forms that were voluntary and anonymous. The educational activity used an adaptation of forum theater, in which participants role-played an instance of oppression with a goal of altering the ultimate outcome. This approach provided participants with the opportunity to develop and rehearse responses to workplace bias in a way that preserved the provider-patient relationship. Results Feedback for these educational sessions was overwhelmingly positive. Participants noted the importance of acknowledging and addressing bias in the workplace and encouraged facilitators to expand the sessions in length, frequency, and scope. Discussion Forum theater is a methodology that can be employed in health care to teach appropriate and authentic responses to expressed patient bias while maintaining the therapeutic relationship. The positive reception from participants in our preliminary sessions established a strong foundation for future improvements to this work.

It is well established that cancer and its treatment, whether by chemotherapy, radiotherapy, hormone therapy, or surgery, can adversely impact reproductive function in both women and men. The effects of cancer treatment on reproductive function in both sexes may lead to loss of fertility, sexual desire and function, and hormone deficiency, which results in additional long-term morbidity in more than a third of patients. Given the importance of reproductive function to most people, and the often devastating effect of cancer treatment on it, we propose that proactive assessment of the functional and endocrinological impact of treatment be made a vital component of the assessment of modern cancer treatment, and should be a routine part of discussions with patients before and after treatment, both in trials and in routine care. Reproductive counselling should be proactive and encouraged, as implementation of such counselling has been shown to be beneficial to patient mental health, quality of life, and adherence to treatment. Similarly, efforts should be made to provide more adequate and accurate information to patients, as well as to offer appropriate fertility preservation approaches, which may potentially influence their treatment decisions., SCOPUS: ar.j, info:eu-repo/semantics/published

Background: Multi-parameter gene expression assays (MPAs) are widely used to estimate individual patient residual risk in hormone-sensitive HER2-negative node-negative early breast cancer, allowing patients with low risk to safely avoid chemotherapy. Evidence for MPA use in node-positive breast cancer is limited. OPTIMA (Optimal Personalised Treatment of early breast cancer usIng Multi-parameter Analysis) aims to validate MPA's as predictors of chemotherapy sensitivity in a largely node-positive breast cancer population. Methods: OPTIMA is a partially blinded multi-center, phase 3 randomized controlled trial with an adaptive two-stage design. The main eligibility criteria are women or men aged 40 or older with resected ER-positive, HER2-negative breast cancer and up to 9 involved axillary lymph nodes. Randomization is to standard management (chemotherapy and endocrine therapy) or to MPA-directed treatment. Those with a “high risk” tumor MPA score receive standard management whilst those at “low risk” are treated with endocrine therapy alone. The preliminary phase (OPTIMA prelim) evaluated the performance of several MPAs to select a test to be used in the main efficacy trial based on economic analysis, and assessed the feasibility and acceptability of a large UK trial. OPTIMA prelim used Oncotype DX as the primary discriminator; the main trial will use Prosigna (PAM50) with Prosigna Score ≤60 defined as “low-risk”. The co-primary outcomes are (1) Invasive Disease Free Survival (IDFS) and (2) cost-effectiveness of test-directed therapy. Secondary outcomes include IDFS in “low-risk” patients, quality of life and additional survival measures. An integrated qualitative recruitment study will identify and address challenges to recruitment and informed consent. Tumor blocks from all consenting participants will be banked allowing the performance of alternative MPA technologies to be evaluated. Recruitment of 4500 patients will permit demonstration of 3% non-inferiority of test-directed treatment, with 5% significance and 85% power, assuming 3 years follow-up and a control arm 5-year IDFS of at least 85%. The addition of patients from OPTIMA prelim will allow non-inferiority to be assessed with 2.5% significance. Results: OPTIMA-prelim recruited 412 patients in 23 months from 35 sites with a 47% acceptance rate. The main study opened in January 2017. Early progress indicates that the recruitment target is achievable in the intended 46-month timescale through the participation of >100 sites Conclusion: OPTIMA, as one of two large scale prospective trials validating the use of test-guided chemotherapy decisions in node-positive early breast cancer, is expected to have a global impact on breast cancer treatment. Experience from OPTIMA prelim showed that patient advocate support and close engagement with sites will aid trial success. Funding: The project is funded in the UK by the NIHR HTA Programme (10/34/501). Views expressed are those of the authors and not those of the HTA Programme, NIHR, NHS or the DoH. Citation Format: Stein RC, Makris A, Hughes-Davies L, Macpherson IR, Hall PS, Cameron DA, Earl HM, Pinder SE, Poole CJ, Rea DW, McIntosh S, Harmer V, Morgan A, Rooshenas L, Conefrey C, Donovan JL, Hulme C, McCabe C, Stallard N, Campbell A, Higgins H, Bartlett JMS, Marshall A, Dunn JA. OPTIMA: A prospective randomized trial to validate the predictive utility and cost-effectiveness of gene expression test-directed chemotherapy decisions in early breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT1-06-01.

Objective According to anxiety buffer disruption theory (ABDT), people function effectively in the world, in part, by relying on anxiety-buffer systems to protect against death awareness; however, traumatic experiences can overwhelm and disrupt those anxiety-buffer systems, leaving people unprotected from death awareness and at increased risk for the major symptom clusters of posttraumatic stress disorder (PTSD). Based on that idea, it was hypothesized that (a) when posttraumatic stress symptoms are low, self-affirmation (a known worldview/self-esteem based anxiety-buffer) should prevent mortality reminders from causing increased death-thought accessibility (DTA); but that (b) when posttraumatic stress symptoms are high (indicating anxiety-buffer disruption), self-affirmation should fail to prevent mortality reminders from increasing DTA. Method To test these hypotheses, participants identified in a general population prescreen assessment as "low posttraumatic-stress symptom" (n = 222) and "high posttraumatic-stress symptom" (n = 210) were reminded of death (vs. control topic), prompted to engage in a self-affirmation (vs. nonself-affirmation) task, and then asked to complete a standard assessment of death-thought accessibility (DTA). Results The hypotheses were confirmed, revealing that posttraumatic stress symptoms were associated with the ineffectiveness of anxiety-buffer system in protecting against increased death awareness. Conclusion The present findings support of a foundational concept of ABDT, and point to new insights about the nature of PTSD and its treatment, because failure to manage death awareness is known to cause anxiety and exacerbate anxiety-related disorders (e.g., PTSD). (PsycINFO Database Record

Ziele: Mehr als zwei Millionen Menschen in Großbritannien und Nordirland leben mit einer Krebserkrankung oder haben diese überlebt. Ein Drittel von ihnen berichtet über eine verminderte Lebensqualität. Design: Review der veröffentlichten systematischen Übersichtsarbeiten zur Identifizierung wirksamer, nicht medikamentöser Interventionen zur Verbesserung der Lebensqualität von Krebsüberlebenden. Datenquellen: Folgende Datenbanken wurden bis Mai 2017 durchsucht: PubMed, Cochrane Central, EMBASE, MEDLINE, Web of Science, Cumulative Index to Nursing and Allied Health Literature sowie PsycINFO. Studienauswahl: Eingeschlossen wurden veröffentlichte systematische Übersichtsarbeiten über randomisierte Studien zu nicht medikamentösen Interventionen bei Patienten mit oder nach einer Krebserkrankung, die mindestens 18 Jahre alt waren. Bei allen Teilnehmern war bereits eine Krebserkrankung diagnostiziert worden. Die Interventionen wurden unabhängig vom Setting, d.h. unabhängig davon, ob sie in einer Gesundheitseinrichtung, im häuslichen Umfeld oder internetbasiert durchgeführt wurden, eingeschlossen. Ausgeschlossen waren Übersichtsarbeiten zu alternativen Therapien oder nicht auf Englisch verfasste Berichte. Zwei Wissenschaftler bewerteten unabhängig voneinander Titel, Abstract und den vollständigen Text der Veröffentlichungen und nahmen eine unabhängige Datenextraktion vor. Outcomes: Das primär interessierende Outcome waren alle Maße der globalen (Gesamt-)Lebensqualität. Analysemethoden: Bewertung der Qualität gemäß AMSTAR (Assessment of Multiple Systematic Reviews) und narrative Synthese zur Beurteilung der Wirksamkeit nicht medikamentöser Interventionen und ihrer Komponenten. Ergebnisse: Von 14 430 eindeutigen Titeln wurden 21 in das Review der Übersichtsarbeiten einbezogen. Zwischen den Übersichtsarbeiten bestanden wenige Überschneidungen hinsichtlich der eingeschlossenen Primärveröffentlichungen. 13 Übersichtsarbeiten behandelten unterschiedliche Tumorgruppen, in 7 lag der Schwerpunkt auf Brustkrebs und in einer ging es um Prostatakrebs. Häufig wurden persönliche Interventionen mit internetbasierten oder telefonischen Ansätzen und gedruckten Informationen kombiniert. Die Interventionen umfassten körperliche, psychologische oder verhaltensorientierte, multidimensionale Rehabilitations- und Online-Ansätze. Vorteile hinsichtlich der Lebensqualität zeigten insbesondere Yoga, körperliche Bewegung allgemein, kognitive Verhaltenstherapie (CBT) und Programme zur achtsamkeitsbasierten Stressreduktion (MBSR). Schlussfolgerungen: Bewegungsbasierte Interventionen waren kurzfristig (weniger als 3 bis 8 Monate) und langfristig wirksam. CBT und MBSR waren, insbesondere kurzfristig, ebenfalls mit Vorteilen verbunden. Die Evidenzlage für multidisziplinäre, internetbasierte und edukative Interventionen fiel uneinheitlich aus. Übersetzung aus Duncan M, et al.: BMJ Open 2017;7:e015860 (DOI: 10.1136/bmjopen-2017-015860)

TPS599 Background: Multi-parameter tumor gene expression assays (MPAs) are validated tools to assist adjuvant chemotherapy decisions for post-menopausal women with luminal-type node-negative breast cancer. Currently there is less certainty for women with 1-3 involved axillary lymph nodes and no information on MPA use for patients with higher level nodal involvement. Three RCTs with available data report chemotherapy benefit for premenopausal women; with limited use of ovarian function suppression (OFS) for non-chemotherapy treated participants, chemotherapy-induced menopause may explain these results. Methods: OPTIMA is an international academic, partially-blinded RCT of test-directed chemotherapy treatment with an adaptive design. Women and men aged 40 or older with resected luminal-type breast cancer may participate if they fulfil one of the following stage criteria: pN1-2; pN1mi with pT ≥20mm; pN0 with pT ≥30mm. Consenting patients are randomized between standard treatment with chemotherapy followed by endocrine therapy or to undergo Prosigna testing; those with high-Prosigna Score ( > 60) tumors receive standard treatment whilst those with low-score tumors are treated with endocrine therapy alone. Patients are informed only of their treatment; test details, and randomization for chemotherapy-treated patients are masked. Clinical choice of chemotherapy is declared at randomization from a menu of standard regimens. Endocrine therapy must be for at least 5 years. Women postmenopausal at trial entry should receive an AI; men, tamoxifen; and premenopausal women, either an AI or tamoxifen, and OFS for 3 or more years; OFS initiation may be deferred because of post-chemotherapy amenorrhea. OPTIMA aims to randomize 2250 patients in each arm to demonstrate non-inferiority of test directed treatment, defined as not more than 3% below the estimated 85% 5-year IDFS for the control arm with a one sided 5% significance level. Power is 81% assuming recruitment over 96-months from January 2017 and 12 months minimum follow-up. OPTIMA also has at least 80% power to demonstrate 3.5% non-inferiority of IDFS for patients with low Prosigna Score tumors (estimated 65% of participants). Cox proportional hazards models will be used to explore important prognostic factors including menopausal status. Additional secondary endpoints include DRFI. A cost-effectiveness analysis of protocol specified MPA driven treatment against standard clinical practice will be conducted. At 31/01/2021, 2004 patients had been randomized. The DMC reviewed the trial in December 2020 with knowledge of related trial results and suggested that the trial continues as planned. OPTIMA is registered as ISRCTN42400492 and funded by the UK NIHR Health Technology Assessment Programme, award number 10/34/501. Clinical trial information: ISRCTN42400492.

Introduction Women who have been treated for breast cancer identify vasomotor symptoms, such as hot flushes and night sweats (HFNS), as a serious problem. An estimated 550 000 people live in the UK today with a diagnosis of breast cancer and up to 70% experience HFNS. Estrogen replacement remains the most effective treatment for hot flushes. However, this is contraindicated in the majority of women with estrogen‐dependent breast cancer. Fewer than 50% of women with estrogen receptor (ER) ‐positive breast cancer complete the recommended 5 years of endocrine treatment—tamoxifen and aromatase inhibitors (AIs). This lack of adherence leads to a 20% excess breast cancer mortality. This lack of adherence may be due to unacceptable side effects such as HFNS. Objectives Patient members of the National Cancer Research Institute UK Breast Clinical Studies Group identified that there is very little research into the management of symptoms after breast cancer treatment. In response we established a Working Party on Symptom Management. The members all have a particular interest in the management of HFNS, and include patients, as well as clinical and academic partners representing oncology, psychology, gynaecology, complementary therapies and the voluntary sector. Methods We gauged current clinical practice of the management of HFNS by surveying breast cancer patients, general practitioners (GPs) and healthcare professionals (HCPs) and we will present these data. Results Forty percent of patients reported that no HCPs or GPs had asked them about HFNS. Despite >90% of GPs and HCPs reporting that they prescribed drugs to alleviate HFNS, only 26% of the patients had been offered drugs and fewer than 2% said they helped; 31% of the patients said that the HFNS were severe enough for them to consider stopping endocrine therapy. Conclusion If women are to be helped to adhere to their life‐saving treatment, new approaches need to be developed to ameliorate HFNS.

Objective To evaluate the impact of the QuinteT Recruitment Intervention (QRI) on recruitment in challenging randomized controlled trials (RCTs) that have applied the intervention. The QRI aims to understand recruitment difficulties and then implements “QRI actions” to address these as recruitment proceeds. Study Design and Setting A mixed-methods study, comprising (1) before-and-after comparisons of recruitment rates and the numbers of patients approached and (2) qualitative case studies, including documentary analysis and interviews with RCT investigators. Results Five UK-based publicly funded RCTs were included in the evaluation. All recruited to target. Randomized controlled trial 2 and RCT 5 both received up-front prerecruitment training before the intervention was applied. Randomized controlled trial 2 did not encounter recruitment issues and recruited above target from its outset. Recruitment difficulties, particularly communication issues, were identified and addressed through QRI actions in RCTs 1, 3, 4, and 5. Randomization rates significantly improved after QRI action in RCTs 1, 3, and 4. Quintet Recruitment Intervention actions addressed issues with approaching eligible patients in RCTs 3 and 5, which both saw significant increases in the number of patients approached. Trial investigators reported that the QRI had unearthed issues they had been unaware of and reportedly changed their practices after QRI action. Conclusion There is promising evidence to suggest that the QRI can support recruitment to difficult RCTs. This needs to be substantiated with future controlled evaluations.

To report on the reduction in the surgical site infection (SSI) rate in the Southern Cross Hospitals network over a 12-year period, 2004-2015, following active surveillance and quality improvement actions.Ten hospitals in the network performed prospective SSI surveillance using standard definitions across a range of ten surgical procedure groups. Data was manually collected on a standardised form and entered into a bespoke database. Information collected included timing and dose of surgical antibiotic prophylaxis, type of surgical site skin preparation used, and patient information on smoking, diabetes and body mass index (BMI). Patients were contacted 30 days after their elective surgery to detect SSIs presenting after discharge from hospital. Surveillance results were widely reported to infection control and clinical review committees. Quality improvement activities to increase use of best practice interventions for surgical antibiotic prophylaxis and alcohol-based skin preparations were initiated during the surveillance period.42,792 procedures performed in ten hospitals were analysed. There were 932 (2.2%) SSIs. The SSI rate decreased from 3.5% in 2004 to 1.2% in 2015, r-0.865, p=0.0001, a decrease of 59%, approximately 5% a year. Rates decreased in seven of the 10 hospitals, p≤0.02 for each, and in five of the ten procedure groups, p≤0.02 for each. Diabetic patients, odds ratio (OR) 1.4 (95% confidence interval (CI) 1.1-1.9), obese patients (BMI30), OR 2.0 (95% CI 1.6-2.4), and those with a surgical risk score of ≥1 OR 1.3 (95% CI 1.1-1.6) had higher SSI rates. These three patient risk factors increased during the 12-year period. The use of alcohol-based skin preparations increased during the period from 63% to 84% in the first two and last two years respectively, p0.0001. Use of an alcohol-based skin preparation was associated with a reduction in SSIs OR 0.54 (95% CI 0.47-0.62). On time prophylaxis improved from 72% to 95% over the 12 years, p0.0001, and on time prophylaxis was associated with a reduction in SSIs, OR=0.62 (95% CI 0.51-0.75). The use of 2g doses of cefazolin increased significantly after 2010, p0.0001. The most common cause of SSI was Staphylococcus aureus which was present in 54% of cases with a positive culture.This long-term surveillance and quality improvement programme has made a significant contribution to the overall reduced rate of SSIs in Southern Cross Hospitals. This reduction occurred despite patient risk factors for SSI increasing. Further reduction is possible with higher adherence to best practice and interventions aimed at reducing S. aureus SSIs.

Background: The randomised control trial (RCT) is the most rigorous method of evaluating interventions. Recruitment is often slower and more challenging than expected. The aim of the current paper is to understand the feasibility of recruitment within the NHS and the barriers and motivators to recruitment from the perspective of patients and healthcare professionals (HCPs). Methods: NHS HCPs were surveyed to establish their willingness to participate. Twenty HCPs were interviewed to establish barriers and motivators to recruitment. Eleven patients were interviewed to understand their willingness to participate. Interviews were analysed using thematic analysis. Results: HCP interviews identified key barriers to recruitment: practical barriers included workload and time; clinical barriers included terminology and concern that the trial implied criticism of their current practice; and patient barriers included gender and cultural factors. Motivators to recruitment included: regular communication between research and clinical teams; feedback on findings; and patient and individual benefits for clinicians. Patient interviews suggested that participation in a trial of a psychosocial intervention would strengthen existing coping skills and develop mechanisms for those who were struggling. Conclusions: Survey results demonstrated that recruitment to an RCT of a psychosocial intervention for people living with and beyond cancer would be feasible within the NHS if specific barriers are addressed. From a clinician point of view, barriers should be addressed to improve recruitment, particularly training and education of clinicians and clear communication. From a patient perspective, interventions and RCT should be tailored to target those not routinely represented in RCTs. National Institute for Health Research

Objectives To explore how the concept of randomization is described by clinicians and understood by patients in randomized controlled trials (RCTs) and how it contributes to patient understanding and recruitment. Study Design and Setting Qualitative analysis of 73 audio recordings of recruitment consultations from five, multicenter, UK-based RCTs with identified or anticipated recruitment difficulties. Results One in 10 appointments did not include any mention of randomization. Most included a description of the method or process of allocation. Descriptions often made reference to gambling-related metaphors or similes, or referred to allocation by a computer. Where reference was made to a computer, some patients assumed that they would receive the treatment that was “best for them”. Descriptions of the rationale for randomization were rarely present and often only came about as a consequence of patients questioning the reason for a random allocation. Conclusions The methods and processes of randomization were usually described by recruiters, but often without clarity, which could lead to patient misunderstanding. The rationale for randomization was rarely mentioned. Recruiters should avoid problematic gambling metaphors and illusions of agency in their explanations and instead focus on clearer descriptions of the rationale and method of randomization to ensure patients are better informed about randomization and RCT participation., Highlights • Practices commonly used to describe randomisation in RCT recruitment could confuse patients. • Patients found it difficult to comprehend gambling-related metaphors of randomisation. • Computer-agency descriptions led to patients believing they would receive the best treatment.

Jo Brett,1 Mary Boulton,1 Debbie Fenlon,2 Nick J Hulbert-Williams,3 Fiona M Walter,4 Peter Donnelly,5 Bernadette A Lavery,6 Adrienne Morgan,7 Carolyn Morris,7 Eila K Watson1 1Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, 2College of Human and Health Sciences, Swansea University, Swansea, Wales, 3Department of Psychology, Chester Research Unit for the Psychology of Health, University of Chester, Chester, 4Department of Public Health and Primary Care, University of Cambridge, Cambridge, 5South Devon Healthcare NHS Foundation Trust, Torbay Hospital, Torquay, 6Cancer Services, Oxford University Hospitals Foundation NHS Trust, Oxford, 7Independent Cancer Patients’ Voice, London, UK Introduction: Despite evidence of the efficacy of adjuvant endocrine therapy (AET) in reducing the risk of recurrence and mortality after treatment for primary breast cancer, adherence to AET is suboptimal. This study aimed to explore factors that influence adherence and nonadherence to AET following breast cancer to inform the development of supportive interventions.Methods: Interviews were conducted with 32 women who had been prescribed AET, 2–4years following their diagnosis of breast cancer. Both adherers (n=19) and nonadherers (n=13) were recruited. The analysis was conducted using the Framework approach.Results: Factors associated with adherence were as follows: managing side effects including information and advice on side effects and taking control of side effects, supportive relationships, and personal influences. Factors associated with nonadherence were as follows: burden of side effects, feeling unsupported, concerns about long-term AET use, regaining normality, including valuing the quality of life over length of life, and risk perception.Conclusion: Provision of timely information to prepare women for the potential side effects of AET and education on medication management strategies are needed, including provision of timely and accurate information on the efficacy of AET in reducing breast cancer recurrence and on potential side effects and ways to manage these should they arise. Trust in the doctor–patient relationship and clear patient pathways for bothersome side effects and concerns with AET are important. Training and education on AET for GPs should be considered alongside novel care pathways such as primary care nurse cancer care review and community pharmacist follow-up. Keywords: hormone therapy, oncology, patient experiences, support, follow-up

Introduction All published adjuvant chemotherapy trials in breast cancer have made the assumption that the proportional benefits of chemotherapy apply uniformly across molecular subgroups. However, it can be argued that chemotherapy effectiveness for luminal A breast cancer is low in comparison to other subtypes irrespective of tumour stage. A logical extension of this argument is that novel multiparametric tests that use biological features of breast cancers to assess risk may also inform chemotherapy benefit in luminal cancers. The OPTIMA trial is a multi-centre, partially blinded, randomised clinical trial with a non-inferiority endpoint, and an adaptive design, to compare standard treatment (chemotherapy followed by endocrine therapy) with multi-parameter test-guided treatment allocation to either chemotherapy followed by endocrine therapy or endocrine therapy alone. OPTIMA-prelim aimed to compare the predicted risk stratification, sub-type classification and cost effectiveness of different multiparameter tests performed on the same patient population. Methods Over 20 months of recruitment 285 patients were randomised to OPTIMA-prelim. Tissue was collected centrally, ER and HER2 status confirmed and samples provided for testing with Oncotype DX™, Prosigna™ (PAM50), Mammaprint™, Mammatyper™, IHC4-AQUA and IHC4 using conventional biomarkers. Sub-type classification was provided by Blueprint™, Mammatyper™ and Prosigna™. Each test was performed at central diagnostic laboratories (OncotypeDx, Mammaprint/Blueprint, Mammatyper) or in a central laboratory (Prosigna™/IHC4) strictly according to GLP practices. Results Samples from 181 patients randomised by January 2014 were tested and data analysed for this study. Patients were categorised as low/intermediate or high risk using predetermined cut-offs for each test. Oncotype DX predicted a proportion of low-risk tumours (79%; 95% CI 73-85%) similar to that predicted as either low or intermediate risk using Prosigna ROR_P (71%; 95% CI 64-78%) and IHC4 (69%; 95% CI 62-76%), whilst MammaPrint identified the fewest low-risk tumours (59%; 95% CI 52-66%). Strikingly, a comparison between tests showed modest agreement between tests when dichotomising results between high vs low/intermediate risk. Disagreement between different tests, in assigning individual tumours to risk categories, is not uncommon; for the four tests [Oncotype DX, MammaPrint, Prosigna ROR_P (low/int) and IHC4 (low/int)], only 71 (39%) tumours were classified as low/intermediate risk for all four tests and only 17 (9%) tumours were high risk for all four tests, 93 (52%) tumours were assigned to different risk categories by different tests. Similarly all three subtypes tests (Blueprint/Prosigna/Mammatyper) each assigned 59% of tumors to luminal A subtype but only 70% of these cases were classified as luminal A by all three assays. Conclusion Existing evidence on the comparative prognostic information provided by different tests suggests current multiparameter tests provide broadly equivalent risk information for the population of women with luminal breast cancers. However, for the individual patient, tests may provide differing risk categorisation or indeed subtype information. Acknowledgement This project was funded by the NIHR Health Technology Assessment (HTA) Programme (project 10/34/01). The opinions expressed therein are those of the authors and do not necessarily reflect those of the HTA programme, NIHR, NHS or Department of Health. Citation Format: John MS Bartlett, Robert C Stein, Jane Bayani, Andrea Marshall, Janet A Dunn, Amy F Campbell, Carrie Cunningham, Monika Sobol, Peter Hall, Leila Rooshenas, Adrienne Morgan, Christopher Poole, Sarah E Pinder, David A Cameron, Nigel Stallard, Jenny Donovan, Christopher McCabe, Luke Hughes-Davies, Andreas Makris, on Behalf of the OPTIMA Trial Management Group. Comparison of multiparameter tests in the UK OPTIMA-Prelim trial [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-11-07.

Aberrant promoter DNA hypermethylation is a hallmark of cancer; however, whether this is sufficient to drive cellular transformation is not clear. To investigate this question, we use a CRISPR-dCas9 epigenetic editing tool, where an inactive form of Cas9 is fused to DNA methyltransferase effectors. Using this system, here we show simultaneous de novo DNA methylation of genes commonly methylated in cancer, CDKN2A, RASSF1, HIC1 and PTEN in primary breast cells isolated from healthy human breast tissue. We find that promoter methylation is maintained in this system, even in the absence of the fusion construct, and this prevents cells from engaging senescence arrest. Our data show that the key driver of this phenotype is repression of CDKN2A transcript p16 where myoepithelial cells harbour cancer-like gene expression but do not exhibit anchorage-independent growth. This work demonstrates that hit-and-run epigenetic events can prevent senescence entry, which may facilitate tumour initiation., “Although aberrant promoter DNA hypermethylation is a hallmark of cancer, it is not clear whether it is sufficient to drive transformation. Here, the authors use CRISPR-dCas9 to perform hit-and-run epigenetic editing, which prevents senescence entry in primary breast cells from healthy donors.”

Background Precision medicine is heralded as offering more effective treatments to smaller targeted patient populations. In breast cancer, adjuvant chemotherapy is standard for patients considered as high-risk after surgery. Molecular tests may identify patients who can safely avoid chemotherapy. Objectives To use economic analysis before a large-scale clinical trial of molecular testing to confirm the value of the trial and help prioritize between candidate tests as randomized comparators. Methods Women with surgically treated breast cancer (estrogen receptor–positive and lymph node–positive or tumor size ≥30 mm) were randomized to standard care (chemotherapy for all) or test-directed care using Oncotype DX™. Additional testing was undertaken using alternative tests: MammaPrint TM , PAM-50 (Prosigna TM ), MammaTyper TM , IHC4, and IHC4-AQUA™ (NexCourse Breast™). A probabilistic decision model assessed the cost-effectiveness of all tests from a UK perspective. Value of information analysis determined the most efficient publicly funded ongoing trial design in the United Kingdom. Results There was an 86% probability of molecular testing being cost-effective, with most tests producing cost savings (range −£1892 to £195) and quality-adjusted life-year gains (range 0.17–0.20). There were only small differences in costs and quality-adjusted life-years between tests. Uncertainty was driven by long-term outcomes. Value of information demonstrated value of further research into all tests, with Prosigna currently being the highest priority for further research. Conclusions Molecular tests are likely to be cost-effective, but an optimal test is yet to be identified. Health economics modeling to inform the design of a randomized controlled trial looking at diagnostic technology has been demonstrated to be feasible as a method for improving research efficiency.

This study evaluated the Beliefs about Medicine Questionnaire to explore adherence to adjuvant endocrine therapy after treatment for breast cancer (BMQ-AET). Factor structure of the BMQ-AET was explored alongside internal consistency, convergent validity and acceptability. The BMQ-AET Specific Scale fitted the original 10 item model. Internal consistency of the BMQ-AET was much improved compared to the original BMQ and convergent validity showed predicted direction of correlation, although correlation with BMQ-AET concerns scale was low. Acceptability was good. The evaluation of the BMQ-AET is encouraging, and could facilitate future research around adherence to AET.

More and more people are living with the consequences of cancer and its treatment (living with and beyond cancer), yet the level of relevant research is low compared to other types of cancer research in the UK. NCRI aims to increase the level of research in this area and to ultimately improve the lives of those affected by cancer. Undefined research priorities in this broad area has been a barrier to research. The 2015 NHS Independent Cancer Taskforce report also recommends defining research priorities and to enable this research to happen. To address this barrier the NCRI has undertaken a James Lind Alliance Priority Setting Partnership (PSP) to identify priorities that matter most to people affected by cancer and the health and social care professionals.A PSP consists of patients and carers, health and social care professionals. PSPs have several stages and begin with a UK-wide survey to gather questions about uncertainties in living with and beyond cancer. Once the results were analysed, an interim exercise takes place to further prioritise the uncertainties. The last stage is a final workshop where partners debate and finally arrive at a top 10 list of shared uncertainties.The living with and beyond cancer PSP received 3500 questions submitted by people affected by cancer and healthcare professionals. Through a 18-month established rigorous process, the questions are prioritised down to the Top 10 living with and beyond cancer priorities for research in June 2018. This is the first time that clear research priorities have been identified in this area. They are the most impactful research questions that will help improve the lives of people affected by cancer. The Top 10 uncertainties will be publicised widely to ensure that researchers and those who fund research really understand what matters to people affected by cancer. The top uncertainties will be promoted to many research organizations and relevant funders in the UK. We anticipate they will directly influence future research. Citation Format: Feng Li, Adrienne Morgan, Angela McCullagh, Anne Johnson, Ceinwen Giles, Diana Greenfield, Graeme Crawford, Jacqui Gath, Jane Lyons, Jervoise Andreyev, Jonathan Tobutt, Julia Tugwell, Karen Robb, Laura Cove-Smith, Lindsey Bennister, Natalie Doyle, Nicolas Lee, Rebecca Nash, Richard Simcock, Richard Stephens, Sabine Best, Susan Moug, Kristina Staley, Sandra Regan, Patricia Ellis, Stuart Griffiths, Ian Lewis. Top 10 living with and beyond cancer research priorities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3348.

Background There is uncertainty about the benefit of chemotherapy for some patients with ER-positive HER2-negative early breast cancer. Multi-parameter assays of gene expression may enhance the value of chemotherapy through personalised treatment decisions. An economic evaluation was undertaken in the context of the feasibility phase of an RCT (OPTIMA prelim) designed to validate prospectively the use of such an assay as a treatment decision tool in the UK National Health Service (NHS). The aim of the economic evaluation was to confirm value in an ongoing RCT and optimise its design for economic endpoints. Comparators included (i) All patients treated with chemotherapy, (ii) Oncotype DX, (iii) MammaPrint/BluePrint and (iv) Prosigna. Methods A model-based cost-effectiveness analysis was conducted to the standards of the UK National Institute for Care Excellence (NICE) reference case. A Markov model was constructed to simulate the care pathway of a cohort of patients with characteristics identified in the OPTIMA prelim study or, where unavailable, from the published literature. The costs (GBP) and benefits (QALYs) were estimated over a time horizon of the patient life-time. Alternative scenarios of recurrence rates and chemotherapy effect were explored in patients identified high or low risk by the tests and treated with and without chemotherapy. Scenarios included estimates based on the SWOG-8814 trial, the EBCTCG and outcomes forecasted using Adjuvant! Online. Uncertainty introduced by discrepancy in patient selection between tests was modelled using a Bayesian decision analytic framework. Probabilistic sensitivity analysis and value of information analysis was conducted using Monte Carlo simulation. Results There were 285 randomised patients. Multi-parameter analyses were performed on tumour samples and baseline factors were included in the model. The cost-effectiveness of all tests was uncertain. Uncertainty was predominantly driven by assumptions about long term recurrence rates in test-selected groups and the ability of tests to predict benefit from chemotherapy. The relationship between recurrence-free survival and life expectancy in test-selected groups and in patients who did or did not receive adjuvant chemotherapy was also important. The incremental cost-effectiveness ratio (ICER) for Oncotype DX compared with chemotherapy for all was cost-effective in many scenarios, ranging from GBP26,000 per QALY to resulting in increased QALYs with cost savings (dominate), depending on assumptions. The value of information analysis placed high societal value in further research into recurrence-free survival for test-directed chemotherapy, irrespective of the test evaluated. Conclusion There is substantial value in prospective comparative research into all tests evaluated, including long term outcomes, to resolve uncertainties in the clinical and economic optimal choice of test. Acknowledgements This project was funded by the National Institute for Health Research Health Technology Assessment (NIHR HTA) Programme (project number 10/34/01). The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the HTA programme, NIHR, NHS or the Department of Health. Citation Format: Peter S Hall, Alison F Smith, Armando Vargas-Palacios, Robert C Stein, John Bartlett, Jane Bayani, Andrea Marshall, Janet A Dunn, Amy F Campbell, Carrie Cunningham, Leila Rooshenas, Monika Sobol, Adrienne Morgan, Christopher Poole, Sarah E Pinder, David A Cameron, Nigel Stallard, Jenny Donovan, Luke Hugh-Davies, Helena Earl, Andreas Makris, Claire Hulme, Christopher McCabe. UK OPTIMA-prelim study demonstrates economic value in more clinical evaluation of multi-parameter prognostic tests in early breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-08-11.

Hot Flushes or Flashes are a serious problem. They impact significantly on daily life and sleep quality, affecting employment, relationships and quality of life. The only effective treatment for hot flushes is oestrogen which is contraindicated in 75% of breast cancer patients. An estimated 550,000 people now live in the UK with a diagnosis of breast cancer and up to 70% women experience disabling hot flushes which can continue for years after treatment. Studies have shown that up to 50% of patients stop taking their life-saving antioestrogen drugs before 5 years1 quite probably due to unacceptable side-effects On the initiative of the patient advocate members of the NCRI Breast Clinical Studies Group, a Working Party on Symptom Management has been established. Members of the group have a particular interest in hot flushes and include representatives from patients, oncology, psychology, gynaecology, acupuncture and the voluntary not-for-profit sector The Working Party audited current UK clinical practice for hot flushes in cancer with a short questionnaire circulated to the UK Breast Intergroup mailing list (about 800 breast cancer health professionals) and to the Breast Cancer Care Nursing Network (about 850 clinical nurse specialists/breast care nurses). The full results of the questionnaire will be presented Briefly, a small number of people were prescribed hormone replacement therapy or Progesterone (Megestrol acatate), more Clonidine and Gabapentin and many selective serotonin reuptake inhibitors (SSRIs). Although SSRIs have some effect in reducing the intensity of hot flushes, they have significant side effects including sexual dysfunction, in a group of women, many of whom are already suffering sexual problems due to anti-oestrogen drugs or premature menopause. In addition, available treatments (both pharmacological and non-pharmacological) varied across the UK. The majority (95%) of respondents to our questionnaire agreed or strongly agreed that treatment and management of hot flushes is an unmet need. The questionnaire also demonstrated inequality of access to treatment in the UK. An exploration of the US National Cancer Institute and UK clinical trials databases revealed very few studies working in this area. 21 studies in the UK, Europe and the USA since 2006. Most trials investigate non pharmacological approaches and combinations and new versions of existing approaches. There are no agreed guidelines for managing hot flushes after breast cancer, which may limit the access and availability of appropriate interventions. It is clear from our survey that clinicians are left making individual decisions based on personal experience and availability of local services, which has led to a patchy and inequitable position on the management of this troubling problem. There is a need for research to understand the physiology of flushing and to develop and test new interventions to address this intractable problem, which continues to be a cause of considerable distress to many women after breast cancer. 1. Makubate B et al Cohort study of adherence to adjuvant endocrine therapy, breast cancer recurrence and mortality.Br J Cancer. 2013;108:1515-24. This project was funded by the National Institute for Health Research Health Technology Assessment (NIHR HTA) Programme (project number 10/34/01). The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the HTA programme, NIHR, NHS or the Department of Health. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-08-09.

The Breast Cancer Campaign Tissue Bank (BCCTB) was initiated in 2010 after the charity Breast Cancer Campaign heard from breast cancer experts that insufficient high quality breast cancer tissue was preventing research which would impact people with breast cancer1. The charity decided to involve patient advocates in the development of the BCCTB from the beginning. Two advocates reviewed the initial applications to form the BCCTB. These included both single and multi-centre applications so they suggested that, rather than choosing one centre to form the Bank, the charity consider a collaboration of centres. Throughout the development of the BCCTB, the patient advocates asked the ‘elephant in the room’ questions and brought a different perspective. They also helped to design the Bank's processes, including the consent process and asking that all tissue applicants produce a lay summary of their research. There are now two advocates on the Board which provides strategic direction to the BCCTB. The advocates have equal status to other Board members. There are also three advocates on the Tissue Access Committee which controls the use of tissue in the Bank. Lay summaries of projects have to be approved by all advocates before an application can proceed. This means that no precious tissue is released without the approval of a lay person, who can ensure maximum patient benefit will be achieved from any research. The Bank's data return policy was also driven by the patient advocates who were keen that the tissues donated were used to their maximum benefit. This has resulted in the first publication from BCCTB2 Patient advocates have been involved in promoting the use of tissue from the bank presenting at conferences and at BCCTB road shows. Patient advocates have also been involved in asking potential donors to consent to donate to the tissue bank. The involvement of patient advocates in the development and oversight of the BCCTB has shown researchers that patient and public involvement works. The advocates can also help promote the Bank and the benefits of tissue donation to both professionals and lay groups. The patient advocates involved in the Breast Cancer Campaign Tissue Bank are members of the charity Independent Cancer Patients’ Voice 1. Thompson P, Brennan K, Cox A, Gee J, Harcourt D, Harris A, Harvie M, Holen I, Howell A, Nicholson R, Steel M, Streuli C. Evaluation of the current knowledge limitations in breast cancer research: a gap analysis. Breast Cancer Res 2008: 10(2); R26. 2. Speirs V, Morgan A. Investment biobanking – increased returns on tissue samples. Nat Rev Clin Onc 2013; 10:128-129. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-10-01.

Adherence to adjuvant endocrine therapy (AET) following breast cancer is known to be suboptimal despite its known efficacy in reducing recurrence and mortality. This study aims to investigate factors associated with non-adherence and inform the development of interventions to support women and promote adherence. A questionnaire survey to measure level of adherence, side effects experienced, beliefs about medicine, support received and socio-demographic details was sent to 292 women 2–4 years post breast cancer diagnosis. Differences between non-adherers and adherers to AET were explored, and factors associated with intentional and unintentional non-adherence are reported. Approximately one quarter of respondents, 46 (22%), were non-adherers, comprising 29 (14%) intentional non-adherers and 17 (8%) unintentional non-adherers. Factors significantly associated with intentional non-adherence were the presence of side effects (p < .03), greater concerns about AET (p < .001) and a lower perceived necessity to take AET (p < .001). Half of the sample (105/211) reported that side effects had a moderate or high impact on their quality of life. Factors associated with unintentional non-adherence were younger age (

Follow-up after treatment for cancer currently varies widely depending on the hospital, surgeon, oncologist, cancer diagnosis and sometimes the wishes of the patient. There seems to be no gold standard. Some are followed up frequently with scans, blood tests and physical examinations for anything up to and beyond 10 years. Others are offered ‘open access’ or ‘patient-led’ follow-up and some are referred back to their general practitioner with a guarantee of rapid access back to hospital appointments in the event of signs of recurrence. This editorial addresses follow-up and related survivorship issues from the patient’s view point.

TPS623Background: Multi-parameter gene expression assays (MPAs) are widely used to estimate individual patient residual risk and guide chemotherapy use in hormone sensitive HER2-ve early breast cancer, but prospective validation data are not available. OPTIMA aims to validate the use of MPA testing to predict chemotherapy sensitivity in a largely node-positive breast cancer population. Methods: OPTIMA is a partially blinded multi-center, phase 3 RCT with an adaptive two-stage design. The preliminary phase (OPTIMA prelim) evaluated the performance of MPAs to identify a suitable test to be used in the main efficacy trial, and demonstrated the feasibility and acceptability of a large UK trial. Eligible patients (pts) are men or women aged ≥ 40 years who have surgically resected early stage ER+ve and HER2-ve breast cancer, and have either 1-9 involved axillary lymph nodes or tumors of ≥ 30mm diameter. Randomization is to standard management (chemotherapy followed by endocrine therapy) or to MPA-directed thera...

ObjectivesOver two million people in the UK are living with and beyond cancer. A third report diminished quality of life.DesignA review of published systematic reviews to identify effective non-pharmacological interventions to improve the quality of life of cancer survivors.Data sourcesDatabases searched until May 2017 included PubMed, Cochrane Central, EMBASE, MEDLINE, Web of Science, the Cumulative Index to Nursing and Allied Health Literature, and PsycINFO.Study selectionPublished systematic reviews of randomised trials of non-pharmacological interventions for people living with and beyond cancer were included; included reviews targeted patients aged over 18. All participants had already received a cancer diagnosis. Interventions located in any healthcare setting, home or online were included. Reviews of alternative therapies or those non-English reports were excluded. Two researchers independently assessed titles, abstracts and the full text of papers, and independently extracted the data.OutcomesThe primary outcome of interest was any measure of global (overall) quality of life.Analytical methodsQuality assessment assessing methdological quality of systematic reviews (AMSTAR) and narrative synthesis, evaluating effectiveness of non-pharmacological interventions and their components.ResultsOf 14 430 unique titles, 21 were included in the review of reviews. There was little overlap in the primary papers across these reviews. Thirteen reviews covered mixed tumour groups, seven focused on breast cancer and one focused on prostate cancer. Face-to-face interventions were often combined with online, telephone and paper-based reading materials. Interventions included physical, psychological or behavioural, multidimensional rehabilitation and online approaches. Yoga specifically, physical exercise more generally, cognitive behavioural therapy (CBT) and mindfulness-based stress reduction (MBSR) programmes showed benefit in terms of quality of life.ConclusionsExercise-based interventions were effective in the short (less than 3–8 months) and long term. CBT and MBSR also showed benefits, especially in the short term. The evidence for multidisciplinary, online and educational interventions was equivocal.

As a part of the Double Helix curriculum at the University of Rochester School of Medicine and Dentistry, six themes are addressed throughout 4 years of medical education. One of these themes is that of diversity. The goal of the diversity theme curriculum is to have students develop an understanding of how features of culture and society, economy, and social structures are related to health and disease in populations. This resource contains a three-part activity that includes a student narrative, an interactive large-group activity, and small-group work. The student narrative is prepared in advance while the large- and small-group activities are conducted in the course of a half day. The small-group work allows for debriefing from the large-group activity as well as for students' to provide peer feedback regarding the patient experiences outlined in their narratives. Expert faculty feedback is provided in addition through written critique of the narratives. These materials can be used for students who are at any level of training as long as they are interfacing with real patients. In general, the presentation is well received by the students. Although we do not have a pre- or postassessment data, we have noted that a number of students come to speak independently to speak with the course director, and ask for further insights or resources pertaining to the content.

Women who have been treated for breast cancer identify vasomotor symptoms, such as hot flushes and night sweats, as a serious problem. These symptoms can be unpleasant, with a significant impact on daily life and sleep quality: It’s as though somebody has built a furnace inside of you and it’s your whole body. It starts almost at your feet and works up and you just feel as though you are literally on fire inside and it’s trying to escape and you just want to escape but you can’t escape, there’s nowhere to go and nothing to do [1]. The social consequences of this embarrassing experience can affect employment, personal relationships and quality of life: Umm, when they were at their worst I would be yeah pretty much dripping in, in err, various places umm err from really from the nose downwards; the lips; the neck; umm chest and back; crooks of my arms. And I could, you know, often if I was sitting down I would get up and my trousers would be really wet and it would go right down to my toes [1]. Oestrogen replacement remains the most effective treatment for hot flushes. However, this is contraindicated in the majority of women with oestrogen-dependent breast cancer. An estimated 550 000 people live in the UK today with a diagnosis of breast cancer and up to 70% experience hot flushes [2e5], which are exacerbated by a lack of safe and effective management strategies [4]. Although hot flushes may occur for a number of reasons, including natural or chemotherapy-induced menopause, they may also be side-effects of adjuvant hormonal therapies, such as tamoxifen and the aromatase inhibitors. Two recent clinical trials (aTTom [6] and ATLAS [7]) showed that 10 years of tamoxifen significantly reduces the risk of recurrence and breast cancer mortality. However, an increasing number of studies report that over 50% of women do not adhere to 5 years of endocrine treatment with an associated increase in mortality [8]. The lack of effective management of vasomotor symptoms may be an important contributory factor to this lack of adherence [9]. The pathophysiology of hot flushes is poorly understood. Proposed mechanisms include altered peripheral vascular reactivity and a narrowed thermoneutral zone [10], although how this relates to oestrogen deprivation is not understood. Without a fuller understanding of the physiology, mechanisms and triggers it will be difficult to develop new targeted therapies. Adrienne Morgan says ‘I was diagnosed with breast cancer eight years ago and continue to take anti-oestrogen drugs because my cancer has returned. I have had a hot flush every 45 minutes for the last eight years. It is difficult to convey to anyone who has never had a hot flush how awful they are; exhausting, embarrassing, agitating.. I am fatigued, unable to work, sleep is only possible with medication and every morning my bed is soaked. I have tried everything. Only the SSRIs have some effect by reducing the severity of the hot flushes (venlafaxine made me feel horrible so I take Citalopram)but they make me anorgasmic. It surprises me that there is not more basic research being done into the causes of hot flushes. After all, most women will have them at some stage in their lives - not just breast cancer patients - and now men with prostate cancer are getting them too’.

Background: Multi-parameter gene expression assays (MPAs) are widely used to estimate individual patient residual risk and to guide chemotherapy use in hormone-sensitive HER2-negative node-negative early breast cancer. These uses of MPAs have not yet been prospectively validated. OPTIMA aims to validate the use of MPA testing to predict chemotherapy sensitivity in a largely node-positive breast cancer population. Methods: OPTIMA is a partially blinded multi-center, phase 3 randomized controlled trial with an adaptive two-stage design. The preliminary phase (OPTIMA prelim) evaluated the performance of MPAs to identify a suitable test(s) to be used in the main efficacy trial and assessed the feasibility and acceptability of a large UK trial. Eligible patients are men or women aged 40 years or older who have surgically resected early stage breast cancer, which is ER-positive and HER2-negative and who have either 1-9 involved axillary lymph nodes or tumors of at least 30mm diameter. Randomization is to standard management (chemotherapy followed by endocrine therapy) or to MPA-directed treatment. Those with a tumor categorized as "high-risk" by the test will be assigned to standard management whilst those at "low-risk" will be treated with endocrine therapy alone. OPTIMA prelim used Oncotype DX as the primary discriminator; the main trial will use Prosigna (PAM50). The co-primary outcomes are (1) Invasive Disease Free Survival (IDFS) and (2) cost-effectiveness of test-directed therapy compared to standard practice. Secondary outcomes include IDFS in "low-risk" patients, distant disease free survival, breast cancer specific survival, overall survival and quality of life. An integrated qualitative recruitment study will identify and address challenges to recruitment and informed consent. Tumor blocks from all consenting participants will be banked allowing the performance of alternative MPA technologies to be evaluated. Recruitment of 4500 patients over 4 years will permit demonstration of 3% non-inferiority of test-directed treatment, with 5% significance and 85% power, assuming 3 years follow-up and a control arm 5-year IDFS of at least 85%. The addition of patients from OPTIMA prelim will allow non-inferiority to be assessed with 2.5% significance. Results: OPTIMA-prelim recruited 412 patients in 23 months from 35 sites. It confirmed the acceptability of randomization to patients with a 47% acceptance rate, and to clinicians and hence the feasibility of a large prospective trial of test-directed treatment running in 100-plus UK sites. It showed that investment into research on test-directed therapy, especially with Prosigna, should be of substantial value to the NHS. Conclusion: OPTIMA, as one of two large scale prospective trials validating the use of test-guided chemotherapy in node-positive hormone-sensitive early breast cancer will have a global impact on patient treatment. Recruitment into the main efficacy trial will commence in October 2015. Funding: Project funded by the UK NIHR HTA Programme (10/34/501). Views expressed are those of the authors and not those of the HTA Programme, NIHR, NHS or the DoH. Citation Format: Stein RC, Marshall A, Hall PS, Bartlett JMS, Rooshenas L, Campbell A, Cameron DA, Rea D, Macpherson I, Earl HM, Poole CJ, Francis A, Morgan A, Harmer V, Pinder SE, Stallard N, Donovan J, Hulme C, McCabe C, Hughes-Davies L, Makris A, Dunn JA. OPTIMA (optimal personalised treatment of early breast cancer usIng multi-parameter analysis), a prospective trial to validate the predictive utility and cost-effectiveness of gene expression test-directed chemotherapy decisions. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT3-02-12.

The mortality from breast cancer has improved steadily over the past two decades, in part because of the increased use of more effective adjuvant therapies. Thousands of women are routinely treated with intensive chemotherapy, which can be unpleasant, is expensive and is occasionally hazardous. Oncologists have long known that some of these women may not need treatment, either because they have a low risk of relapse or because they have tumour biology that makes them less sensitive to chemotherapy and more suitable for early adjuvant endocrine therapy. There is an urgent need to improve patient selection so that chemotherapy is restricted to those patients who will benefit from it. Here we review the emerging technologies that are available for improving patient selection for chemotherapy. We describe the OPTIMA trial, which has just opened to recruitment in the UK, is the latest addition to trials in this area, and is the first to focus on the relative cost-effectiveness of alternate predictive assays.

Multi-parameter gene expression assays (MPA) to aid selection of chemotherapy in hormone-sensitive early breast cancer have not been prospectively validated. This field of personalised medicine is rapidly evolving. There is currently no “best test”. OPTIMA is an adaptive trial of MPA-based chemotherapy assignment in a largely node-positive breast cancer population.