Atypia detected during breast screening and subsequent development of cancer: observational analysis of the Sloane atypia prospective cohort in England.

OBJECTIVE: To explore how the number and type of breast cancers developed after screen detected atypia compare with the anticipated 11.3 cancers detected per 1000 women screened within one three year screening round in the United Kingdom. DESIGN: Observational analysis of the Sloane atypia prospective cohort in England. SETTING: Atypia diagnoses through the English NHS breast screening programme reported to the Sloane cohort study. This cohort is linked to the English Cancer Registry and the Mortality and Birth Information System for information on subsequent breast cancer and mortality. PARTICIPANTS: 3238 women diagnosed as having epithelial atypia between 1 April 2003 and 30 June 2018. MAIN OUTCOME MEASURES: Number and type of invasive breast cancers detected at one, three, and six years after atypia diagnosis by atypia type, age, and year of diagnosis. RESULTS: There was a fourfold increase in detection of atypia after the introduction of digital mammography between 2010 (n=119) and 2015 (n=502). During 19 088 person years of follow-up after atypia diagnosis (until December 2018), 141 women developed breast cancer. Cumulative incidence of cancer per 1000 women with atypia was 0.95 (95% confidence interval 0.28 to 2.69), 14.2 (10.3 to 19.1), and 45.0 (36.3 to 55.1) at one, three, and six years after atypia diagnosis, respectively. Women with atypia detected more recently have lower rates of subsequent cancers detected within three years (6.0 invasive cancers per 1000 women (95% confidence interval 3.1 to 10.9) in 2013-18 v 24.3 (13.7 to 40.1) in 2003-07, and 24.6 (14.9 to 38.3) in 2008-12). Grade, size, and nodal involvement of subsequent invasive cancers were similar to those of cancers detected in the general screening population, with equal numbers of ipsilateral and contralateral cancers. CONCLUSIONS: Many atypia could represent risk factors rather than precursors of invasive cancer requiring surgery in the short term. Women with atypia detected more recently have lower rates of subsequent cancers detected, which might be associated with changes to mammography and biopsy techniques identifying forms of atypia that are more likely to represent overdiagnosis. Annual mammography in the short term after atypia diagnosis might not be beneficial. More evidence is needed about longer term risks.

Evidence-informed recommendations on managing breast screening atypia: perspectives from an expert panel consensus meeting reviewing results from the Sloane atypia project.

Evidence-based clinical guidelines are essential to maximize patient benefit and to reduce clinical uncertainty and inconsistency in clinical practice. Gaps in the evidence base can be addressed by data acquired in routine practice. At present, there is no international consensus on management of women diagnosed with atypical lesions in breast screening programmes. Here, we describe how routine NHS breast screening data collected by the Sloane atypia project was used to inform a management pathway that maximizes early detection of cancer and minimizes over-investigation of lesions with uncertain malignant potential. A half-day consensus meeting with 11 clinical experts, 1 representative from Independent Cancer Patients' Voice, 6 representatives from NHS England (NHSE) including from Commissioning, and 2 researchers was held to facilitate discussions of findings from an analysis of the Sloane atypia project. Key considerations of the expert group in terms of the management of women with screen detected atypia were: (1) frequency and purpose of follow-up; (2) communication to patients; (3) generalizability of study results; and (4) workforce challenges. The group concurred that the new evidence does not support annual surveillance mammography for women with atypia, irrespective of type of lesion, or woman's age. Continued data collection is paramount to monitor and audit the change in recommendations.

Mastectomy patterns among older women with early invasive breast cancer in England and Wales: A population-based cohort study.

INTRODUCTION: Older women with early invasive breast cancer (EIBC) are more likely to receive a mastectomy compared with younger women. This study assessed factors associated with receiving a mastectomy among older women with EIBC, with a particular focus on comorbidity and frailty. MATERIALS AND METHODS: Women diagnosed with EIBC (stages I-IIIa) aged ≥50 years from 2014 to 2019 in English and Welsh NHS organisations who received breast surgery were identified from cancer registration datasets linked to routine hospital data. Separate multivariable logistic regression models explored factors associated with mastectomy use, within each tumour stage (T1-T3). For each tumour stage, risk-adjusted rates of mastectomy were calculated for each NHS organisation and displayed using funnel plots. RESULTS: We included 106,952 women with EIBC: 23.4% received a mastectomy as their first breast cancer surgery. Receipt of mastectomy was more common among patients with a higher tumour stage (T1: 12.3%; T2: 37.6%; T3: 77.5%), and mastectomy use increased with age within each tumour stage category (50-59 vs 80 + years: 11.8% vs 26.3% for T1; 31.5% vs 56.9% for T2; 73.4% vs 90.3% for T3). Results from a multivariable regression model showed that more severe frailty was associated with mastectomy use for women with T1 (p = 0.002) or T2 (p = 0.003) tumours, but may not be for women with T3 tumours (p = 0.041). There was no association between comorbidity and mastectomy use after accounting for frailty (all p > 0.1). Adjusting for clinical and patient factors only slightly reduced the association between age and mastectomy use. Variation in mastectomy use between NHS organisations was greatest for women with T2 EIBC (unadjusted range: 17.7% to 68.4%). DISCUSSION: Older women with EIBC are more commonly treated with mastectomy. This could not be explained by tumour characteristics or physical fitness, raising questions about whether surgical decision-making inconsistently incorporates information on patient fitness and functional age.

Association of DCIS size and margin status with risk of developing breast cancer post-treatment: multinational, pooled cohort study.

OBJECTIVE: To examine the association between size and margin status of ductal carcinoma in situ (DCIS) and risk of developing ipsilateral invasive breast cancer and ipsilateral DCIS after treatment, and stage and subtype of ipsilateral invasive breast cancer. DESIGN: Multinational, pooled cohort study. SETTING: Four large international cohorts. PARTICIPANTS: Patient level data on 47 695 women with a diagnosis of pure, primary DCIS between 1999 and 2017 in the Netherlands, UK, and US who underwent surgery, either breast conserving or mastectomy, often followed by radiotherapy or endocrine treatment, or both. MAIN OUTCOME MEASURES: The main outcomes were 10 year cumulative incidence of ipsilateral invasive breast cancer and ipsilateral DCIS estimated in relation to DCIS size and margin status, and adjusted hazard ratios and 95% confidence intervals, estimated using multivariable Cox proportional hazards analyses with multiple imputed data RESULTS: The 10 year cumulative incidence of ipsilateral invasive breast cancer was 3.2%. In women who underwent breast conserving surgery with or without radiotherapy, only adjusted risks for ipsilateral DCIS were significantly increased for larger DCIS (20-49 mm) compared with DCIS <20 mm (hazard ratio 1.38, 95% confidence interval 1.11 to 1.72). Risks for both ipsilateral invasive breast cancer and ipsilateral DCIS were significantly higher with involved compared with clear margins (invasive breast cancer 1.40, 1.07 to 1.83; DCIS 1.39, 1.04 to 1.87). Use of adjuvant endocrine treatment was not significantly associated with a lower risk of ipsilateral invasive breast cancer compared to treatment with breast conserving surgery only (0.86, 0.62 to 1.21). In women who received breast conserving treatment with or without radiotherapy, higher DCIS grade was not significantly associated with ipsilateral invasive breast cancer, only with a higher risk of ipsilateral DCIS (grade 1: 1.42, 1.08 to 1.87; grade 3: 2.17, 1.66 to 2.83). Higher age at diagnosis was associated with lower risk (per year) of ipsilateral DCIS (0.98, 0.97 to 0.99) but not ipsilateral invasive breast cancer (1.00, 0.99 to 1.00). Women with large DCIS (≥50 mm) more often developed stage III and IV ipsilateral invasive breast cancer compared to women with DCIS <20 mm. No such association was found between involved margins and higher stage of ipsilateral invasive breast cancer. Associations between larger DCIS and hormone receptor negative and human epidermal growth factor receptor 2 positive ipsilateral invasive breast cancer and involved margins and hormone receptor negative ipsilateral invasive breast cancer were found. CONCLUSIONS: The association of DCIS size and margin status with ipsilateral invasive breast cancer and ipsilateral DCIS was small. When these two factors were added to other known risk factors in multivariable models, clinicopathological risk factors alone were found to be limited in discriminating between low and high risk DCIS.

Evidence into practice: a national cohort study of NICE-recommended oncological drug therapy utilisation among women diagnosed with invasive breast cancer in England.

BACKGROUND: Multiple drug treatments are approved for invasive breast cancer (IBC). We investigated uptake of NICE-recommended oncological drugs and variation by age, comorbidity burden and geographical region. METHODS: Women (aged 50+ years) diagnosed with IBC from 2014 to 2019, were identified from England Cancer Registry data and drug utilisation from Systemic Anti-Cancer Therapy data. Interrupted time series analysis assessed national-level changes in drug use after publication of NICE recommendations. Regression models analysed variation in use. RESULTS: This national cohort included 168,449 women. Use of drugs recommended for first-line treatment varied, from 26.6% for CDK 4/6 inhibitors to 63.8% for HER2-targeting therapies. Utilisation of drugs with a NICE recommendation published between 2014 and 2019, increased among patients diagnosed around the time of publication, except in the case of pertuzumab for metastatic breast cancer (MBC) which was previously accessible via the Cancer Drugs Fund (though use of pertuzumab for MBC increased from 34.1% to 75.0% across the study period). Use of trastuzumab and neoadjuvant/adjuvant pertuzumab varied by geographical region. Use was low for ribociclib (2.2%), abemaciclib (2.3%) and for drugs recommended beyond the first-line setting. For all drugs, use after NICE recommendation varied by age at diagnosis and increased as stage increased. CONCLUSIONS: Use of NICE-recommended drugs for IBC in routine care is variable, with lowest use among women aged 70+ years. Improving access to effective treatments is an important step in improving outcomes.

Completeness of endocrine therapy information in the Primary Care Prescription Database (PCPD) and secondary care treatment datasets: A national population-based cohort study using routine healthcare data.

BACKGROUND: Endocrine therapy (ET) is a widely used treatment for breast cancer. In the UK, use is typically initiated in secondary care, with subsequent treatment in primary care. Evaluating use of ET depends on data sources containing accurate and complete information. This study aimed to evaluate the completeness and consistency of ET recorded in primary and secondary care data (SCD) and determine the value of combining data sources in describing use of ET. METHODS: This cohort study included women (50 + years) diagnosed with hormone receptor-positive invasive breast cancer in England, April-2015 to December-2019. Concordance of ET recorded in SCD and the Primary Care Prescription Database (PCPD) was evaluated. Factors associated with recording of ET in each setting were assessed using statistical models. RESULTS: Overall 110,529 women were included. 94% had ET recorded in either SCD or PCPD. ET captured in SCD varied from 3% (in Systemic Anti-Cancer Therapy data) to 52% (in the Cancer Outcomes and Services Dataset; COSD). By contrast, 93% of patients had an ET prescription in PCPD. Among patients with ET recorded, this was not captured in COSD for 45%. Capture in COSD was lowest for younger women, those with no comorbidity/frailty, with lower stage or HER2-positive disease, or with other treatments recorded. Overall concordance between COSD and PCPD was 57%, but varied substantially across NHS trusts (lowest decile≤28%; highest decile≥86%). Among women with ET recorded in both settings, the earliest record was in COSD for 97%; 59% of initial ET prescriptions recorded in COSD were not captured in PCPD. Combining PCPD and COSD data enabled estimation of ET duration. CONCLUSIONS: PCPD is vital for understanding the use of ET within this population. Completeness of SCD could be improved by ensuring information on first ET prescription is recorded. PCPD (linked to SCD) is a valuable resource for examining patterns of care for patients with cancer, including treatment duration and adherence.

Concordance of cancer drug therapy information derived from routinely collected hospital admissions data and the Systemic Anti-Cancer Therapy (SACT) dataset, for older women diagnosed with early invasive breast cancer in England.

BACKGROUND: Evaluating uptake of oncological treatments, and subsequent outcomes, depends on data sources containing accurate and complete information about cancer drug therapy (CDT). This study aimed to evaluate the consistency of CDT information in the Hospital Episode Statistics Admitted Patient Care (HES-APC) and Systemic Anti-Cancer Therapy (SACT) datasets for early invasive breast cancer (EIBC). METHODS: The study included women (50 + years) diagnosed with EIBC in England from 2014 to 2019 who had surgery within six months of diagnosis. Concordance of CDT recorded in HES-APC (identified using OPCS codes) and SACT was evaluated at both patient-level and cycle-level. Factors associated with CDT use captured only in HES-APC were assessed using statistical models. RESULTS: The cohort contained 129,326 women with EIBC. Overall concordance between SACT and HES-APC on CDT use was 94 %. Concordance increased over the study period (91-96 %), and there was wide variation across NHS trusts (lowest decile of trusts had concordance≤77 %; highest decile≥99 %). Among women receiving CDT, 9 % (n = 2781/31693) of use was not captured in SACT; incompleteness was worst (18 %=47/259) among women aged 80 + and those diagnosed in 2014 (21%=1121/5401). OPCS codes in HES-APC were good at identifying patient-level and cycle-level use of trastuzumab or FEC chemotherapy (fluorouracil, epirubicin, cyclophosphamide), with 89 % and 93 % concordance with SACT respectively (patient-level agreement). Among cycles of solely oral CDT recorded in SACT, only 24 % were captured in HES-APC, compared to 71 % for intravenous/subcutaneous CDT. CONCLUSIONS: Combining information in HES-APC and SACT provides a more complete picture of CDT treatment in women aged 50 + receiving surgery for EIBC than using either data source alone. HES-APC may have particular value in identifying CDT use among older women, those diagnosed less recently, and in NHS trusts with low SACT data returns.

Cohort profile of the Sloane Project: methodology for a prospective UK cohort study of >15 000 women with screen-detected non-invasive breast neoplasia.

PURPOSE: The introduction of breast screening in the UK led to an increase in the detection of non-invasive breast neoplasia, predominantly ductal carcinoma in situ (DCIS), a non-obligatory precursor of invasive breast cancer. The Sloane Project, a UK prospective cohort study of screen-detected non-invasive breast neoplasia, commenced in 2003 to evaluate the radiological assessment, surgical management, pathology, adjuvant therapy and outcomes for non-invasive breast neoplasia. Long-term follow-up and accurate data collection are essential to examine the clinical impact. Here, we describe the establishment, development and analytical processes for this large UK cohort study. PARTICIPANTS: Women diagnosed with non-invasive breast neoplasia via the UK National Health Service Breast Screening Programme (NHSBSP) from 01 April 2003 are eligible, with a minimum age of 46 years. Diagnostic, therapeutic and follow-up data collected via proformas, complement date and cause of death from national data sources. Accrual for patients with DCIS ceased in 2012 but is ongoing for patients with epithelial atypia/in situ neoplasia, while follow-up for all continues long term. FINDINGS TO DATE: To date, patients within the Sloane cohort comprise one-third of those diagnosed with DCIS within the NHSBSP and are representative of UK practice. DCIS has a variable outcome and confirms the need for longer-term follow-up for screen-detected DCIS. However, the radiology and pathology features of DCIS can be used to inform patient management. We demonstrate validation of follow-up information collected from national datasets against traditional, manual methods. FUTURE PLANS: Conclusions derived from the Sloane Project are generalisable to women in the UK with screen-detected DCIS. The follow-up methodology may be extended to other UK cohort studies and routine clinical follow-up. Data from English patients entered into the Sloane Project are available on request to researchers under data sharing agreement. Annual follow-up data collection will continue for a minimum of 20 years.

Studying the implementation of Zero Suicide in a large health system: Challenges, adaptations, and lessons learned.

Background: Suicide remains the 10th leading cause of death in the United States. Many patients presenting to healthcare settings with suicide risk are not identified and their risk mitigated during routine care. Our aim is to describe the planned methodology for studying the implementation of the Zero Suicide framework, a systems-based model designed to improve suicide risk detection and treatment, within a large healthcare system. Methods: We planned to use a stepped wedge design to roll-out the Zero Suicide framework over 4 years with a total of 39 clinical units, spanning emergency department, inpatient, and outpatient settings, involving ∼310,000 patients. We used Lean, a widely adopted a continuous quality improvement (CQI) model, to implement improvements using a centralize "hub" working with smaller "spoke" teams comprising CQI personnel, unit managers, and frontline staff. Results: Over the course of the study, five major disruptions impacted our research methods, including a change in The Joint Commission's safety standards for suicide risk mitigation yielding massive system-wide changes and the COVID-19 pandemic. What had been an ambitious program at onset became increasingly challenging because of the disruptions, requiring significant adaptations to our implementation approach and our study methods. Conclusions: Real-life obstacles interfered markedly with our plans. While we were ultimately successful in implementing Zero Suicide, these obstacles led to adaptations to our approach and timeline and required substantial changes in our study methodology. Future studies of quality improvement efforts that cut across multiple units and settings within a given health system should avoid using a stepped-wedge design with randomization at the unit level if there is the potential for sentinel, system-wide events.

The presentation, management and outcome of patients with ductal carcinoma in situ (DCIS) with microinvasion (invasion ≤1 mm in size)-results from the UK Sloane Project.

BACKGROUND: The diagnosis, management and prognosis of microinvasive breast carcinoma remain controversial. METHODS: We analysed the outcomes of patients with DCIS with and without microinvasion diagnosed between 2003 and 2012 within the Sloane project. RESULTS: Microinvasion was recorded in 521 of 11,285 patients (4.6%), with considerable variation in reported incidence among screening units (0-25%). Microinvasion was associated with high-grade DCIS, larger DCIS size, comedo necrosis and solid, cribriform architecture (all P < 0.001). Microinvasion was more frequent in patients who underwent mastectomy compared with breast-conserving surgery (BCS) (6.9% vs 3.6%, P < 0.001), and in those undergoing axillary nodal surgery (60.4% vs 30.3%, P < 0.001) including the subset undergoing BCS (43.4% vs 8.5%, P < 0.001). Nodal metastasis rate was low and not statistically significant difference from the DCIS only group (P = 0.68). Following median follow-up of 110 months, 3% of patients had recurrent ipsilateral high-grade DCIS, and 4.2% developed invasive carcinoma. The subsequent ipsilateral invasion was of Grade 3 in 71.4% of patients with microinvasion vs 30.4% in DCIS without microinvasion (P = 0.02). Distant metastasis and breast cancer mortality were higher with microinvasion compared with DCIS only (1.2% vs 0.3%, P = 0.01 and 2.1% vs 0.8%; P = 0.005). CONCLUSIONS: The higher breast cancer mortality with microinvasion indicates a more aggressive disease.

Cost-benefit analysis of sacubitril/valsartan in a Medicaid population.

OBJECTIVE: To evaluate the cost-benefit of sacubitril/valsartan in adults with heart failure (HF) enrolled in a state Medicaid plan to prevent HF-related hospitalizations and emergency department (ED) visits. STUDY DESIGN: Retrospective, claims-based, cost-benefit study. METHODS: This exploratory cost-benefit study evaluated Massachusetts Medicaid (MassHealth) members with HF who had an initial pharmacy claim for sacubitril/valsartan between July 7, 2015, and August 31, 2018 (index date). Efficacy outcomes, HF-related hospitalizations and ED visits, and cost outcomes for HF-related medical and pharmacy claims were compared 1 year pre- and post index date. Benefit-cost ratio and net benefit were calculated for all members. A subgroup analysis evaluated the outcomes for members who were adherent to sacubitril/valsartan. RESULTS: A total of 22 members were identified for the study. There were fewer hospitalizations and ED visits post sacubitril/valsartan initiation in the overall population (post vs pre-: 23 vs 26) and among 12 members adherent to sacubitril/valsartan (10 vs 12). The median (IQR) cost for hospitalizations and ED visits was lower during the postindex period ($576 [$19,439] vs $132 [$11,692]) whereas the median (IQR) cost for HF pharmacotherapies was greater during the postindex period ($4578 [$3033] vs $270 [$255]). The benefit-cost ratio and net benefit were 0.91 and -$336, respectively, for all members and 1.43 and $2337, respectively, for members adherent to sacubitril/valsartan. CONCLUSIONS: The benefit as demonstrated by the cost avoidance of HF-related hospitalizations and ED visits did not outweigh the additional costs of sacubitril/valsartan, but cost-benefit was observed in members who were adherent to sacubitril/valsartan.

Genomic analysis defines clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancer.

Ductal carcinoma in situ (DCIS) is the most common form of preinvasive breast cancer and, despite treatment, a small fraction (5-10%) of DCIS patients develop subsequent invasive disease. A fundamental biologic question is whether the invasive disease arises from tumor cells in the initial DCIS or represents new unrelated disease. To address this question, we performed genomic analyses on the initial DCIS lesion and paired invasive recurrent tumors in 95 patients together with single-cell DNA sequencing in a subset of cases. Our data show that in 75% of cases the invasive recurrence was clonally related to the initial DCIS, suggesting that tumor cells were not eliminated during the initial treatment. Surprisingly, however, 18% were clonally unrelated to the DCIS, representing new independent lineages and 7% of cases were ambiguous. This knowledge is essential for accurate risk evaluation of DCIS, treatment de-escalation strategies and the identification of predictive biomarkers.

Uptake of hepatitis C virus treatment in a multi-state Medicaid population, 2013-2017.

OBJECTIVE: To examine trends in the direct acting antiviral (DAA) uptake in a multi-state Medicaid population with hepatitis C virus (HCV) prior to and after ledipasvir/sofosbuvir (LDV/SOF) approval and changes in prior authorization (PA) requirements. DATA SOURCES: Analyses utilized enrollment, medical, and pharmacy claims in four states, December 2013-December 2017. STUDY DESIGN: An interrupted time series examined trends in uptake (1+ claim for a DAA) before and after two events: LDV/SOV approval (October 2014) and lifting of PA requirements for 40% of members (July 2016). Analyses were also performed in subgroups defined by the number and dates of change in PA requirements in members' Medicaid plans. DATA COLLECTION/EXTRACTION METHODS: Members aged 18-64 years with an ICD code for HCV were included in the sample from diagnosis date until treatment initiation or Medicaid disenrollment. PRINCIPAL FINDINGS: The annual sample size ranged from 38,302 to 45,005 with approximately 30% ages 18-34 years and 40% female. In December 2013, 0.08% was treated, rising to 0.74% in December 2017 (p < 0.001). Uptake increased from 0.34%/month in October 2014 to 0.70%/month after LDV/SOF approval, (p < 0.001), and increased relative to the pre-LDV/SOV trend through June 2016 (p = 0.04). Uptake increased to 1.18%/month after PA change, (p < 0.001) and remained flat through 2017 (p = 0.64). Cumulatively, 20.1% were treated by December 2017. In plans with few/no requirements through 2017, uptake increased to 1.19%/month after LDV/SOF approval (p < 0.001) and remained flat through 2017 (p = 0.11), with 22.2% cumulatively treated. Among plans that lifted PA requirements from three to zero in mid-2016, uptake did not increase after LDV/SOF approval (p = 0.36) but did increase to 1.41%/month (p < 0.001) after PA change, with 18.1% cumulatively treated. CONCLUSIONS: HCV Treatment increased through 2017. LDV/SOF approval and lifting PA requirements led to an increase in uptake followed by flat monthly utilization. Cumulative uptake was higher in plans with few/no PA requirements relative to those with three requirements through mid-2016.

The association between guideline adherence, age and overall survival among women with non-metastatic breast cancer: A systematic review.

INTRODUCTION: Conformity with treatment guidelines should benefit patients. Studies have reported variation in adherence to breast cancer (BC) guidelines, particularly among older women. This study investigated (i) whether adherence to treatment guideline recommendations for women with non-metastatic BC improves overall survival (OS), (ii) whether that relationship varies by age. METHODOLOGY: MEDLINE and EMBASE were systematically searched for studies on guideline adherence and OS in women with non-metastatic BC, published after January 2000, which examined recommendations on breast surgery, chemotherapy, radiotherapy or endocrine therapy. Study results were summarised using narrative synthesis. RESULTS: Sixteen studies met the inclusion criteria. The recommendations for each treatment covered were similar, but studies differed in their definitions of adherence. 5-year OS rates among patients having compliant treatment ranged from 91.3% to 93.2%, while rates among patients having non-compliant treatment ranged from 75.9% to 83.4%. Six studies reported an adjusted hazard ratio (aHR) for non-compliant treatment compared with compliant treatment; all concluded OS was worse among patients whose overall treatment was non-compliant (aHR range: 1.52 [1.30-1.82] to 2.57 [1.96-3.37]), but adjustment for potential confounders was limited. Worse adherence among older women was reported in 12/16 studies, but they did not provide consistent evidence on whether OS was associated with treatment adherence and age. CONCLUSIONS: Individual studies reported that better adherence to guidelines improved OS among women with non-metastatic BC, but the evidence base has weaknesses including inconsistent definitions of adherence. More precise and consistent research designs, including the evaluation of barriers to adherence across the spectrum of healthcare practice, are required to fully understand guideline compliance, as well as the relationship between compliance and OS following a BC diagnosis.

Unresected screen-detected ductal carcinoma in situ: Outcomes of 311 women in the Forget-Me-Not 2 study.

BACKGROUND AND AIM: The natural history of ductal carcinoma in situ (DCIS) is poorly understood. The aim of this cohort study was to determine the outcomes of women who had no surgery for screen-detected DCIS in the 6 months following diagnosis. METHODS: English breast screening databases were retrospectively searched for women diagnosed with DCIS without invasive cancer at screening and who had no record of surgery within 6 months of diagnosis. These were cross-referenced with cancer registry data. Details of the potentially eligible women were sent to the relevant breast screening units for verification and for completion of data forms detailing clinical, radiological and pathological findings, non-surgical treatment and subsequent clinical course. RESULTS: Data for 311 eligible women (median age 62 years) were available. 60 women developed invasive cancer, 56 ipsilateral and 4 contralateral. Ipsilateral invasion risk increased approximately linearly with time for at least 10 years. The 10-year cumulative risk of ipsilateral invasion was 9% (95% CI 4-21%), 39% (24-58%) and 36% (24-50%) for low, intermediate and high grade DCIS respectively and was higher in younger women, in those with larger DCIS lesions and in those with microinvasion. Most invasive cancers that developed were grade 2 or 3. CONCLUSION: The findings suggest that active surveillance may be a reasonable alternative to surgery in patients with low grade DCIS but that women with intermediate or high grade disease should continue to be offered surgery. This highlights the importance of reproducible grading of DCIS to ensure patients receive appropriate treatment.

Breast screening atypia and subsequent development of cancer: protocol for an observational analysis of the Sloane database in England (Sloane atypia cohort study).

INTRODUCTION: The National Health Service (NHS) Breast Screening Programme aims to detect cancer earlier when treatment is more effective but can harm women by over diagnosing and overtreating cancers which would never have become symptomatic. As well as breast cancer, a spectrum of atypical epithelial proliferations (atypia) can also be detected as part of screening. This spectrum of changes, while not cancer, may mean that a woman is more likely to develop breast cancer in the future. Follow-up of atypia is not evidence based. We currently do not know which atypia should be detected to avoid future cancer. This study will explore how atypia develops into breast cancer in terms of number of women, time of cancer development, cancer type and severity, and whether this varies for different types of atypia. METHODS AND ANALYSIS: The Sloane cohort study began in April 2003 with ongoing data collection including atypia diagnosed through screening at screening units in the UK. The database for England has 3645 cases (24 September 2020) of epithelial atypia, with follow-up from 1 to 15 years. The outcomes include subsequent invasive breast cancer and the nature of subsequent cancer. Descriptive statistics will be produced. The observed rates of breast cancer at 1, 3 and 6 years for types of atypia will be reported with CIs, to enable comparison to women in the general population. Time to event methods will be used to describe the time to breast cancer diagnosis for the types of atypia, including flexible parametric modelling if appropriate. Patient representatives from Independent Cancer Patients' Voice are included at every stage of the research. ETHICS AND DISSEMINATION: The study has received research ethics approval from the University of Warwick Biomedical and Scientific Research Ethics Committee (BSREC 10/20-21, 8 October 2020), Public Health England office for data release approvals (ODR1718_313) and approval from the English Breast Research Advisory Committee (BSPRAC_031). The findings will be disseminated to breast screening clinicians (via journal publication and conference presentation), to the NHS Breast Screening Programme to update their guidelines on how women with atypia should be followed up, and to the general public.

Evaluating proactive outreach for prior authorization recertifications in Medicaid patients.

OBJECTIVES: To assess the effectiveness of a proactive provider intervention in prompting prior authorization (PA) submissions or provider response prior to PA expiration for medically complex Medicaid patients. STUDY DESIGN: Pre-post outreach study with data from pharmacy claims and provider outreach. METHODS: The intervention and historical comparison (control) groups included expired PAs from December 2019 to February 2020 and from December 2018 to February 2019, respectively. Provider outreach, including telephonic and fax attempts, was conducted over a 2-week period prior to PA expiration. Outcomes were classified as positive or negative based on provider conversation coupled with the result (eg, PA submission) for the intervention group and based solely on pharmacy claims for the control group. The primary end point was the percentage of positive outcomes between the groups, analyzed via χ2 test. The time from PA expiration to the new PA submission was evaluated via t test. RESULTS: A total of 342 outreach attempts were conducted for 270 PAs representing 193 unique patients. Outreach was more likely to result in positive outcomes in the intervention group vs no outreach in the control group (87% vs 25%; P < .00001). On average, PAs were submitted 3.5 days prior to expiration in the intervention group vs 13.0 days after expiration in the control group (t = -7.50; P < .00001). CONCLUSIONS: Proactive outreach resulted in a greater percentage of PA submissions and a significantly reduced time to PA submission. These findings provide important information for payers in guiding clinical programs to enhance continuity of care among at-risk populations.

Supporting families of children with overweight and obesity to live healthy lifestyles: Design and rationale for the Fitline cluster randomized controlled pediatric practice-based trial.

BACKGROUND: Over a third of preadolescent children with overweight or obesity. The American Academy of Pediatrics (AAP) recommends pediatric providers help families make changes in eating and activity to improve body mass index (BMI). However, implementation is challenging given limited time and referral sources, and family burden to access in-person weight management programs. PURPOSE: To describe the design of a National Heart Blood and Lung Institute sponsored cluster randomized controlled pediatric-based trial evaluating the effectiveness of the Fitline pediatric practice-based referral program to reduce BMI and improve diet and physical activity in children with overweight or obesity. Comparison will be made between brief provider intervention plus referral to (1) eight weekly nutritionist-delivered coaching calls with workbook to help families make AAP-recommended lifestyle changes (Fitline-Coaching), vs. (2) the same workbook in eight mailings without coaching (Fitline-Workbook). METHODS: Twenty practices are pair-matched and randomized to one of the two conditions; 494 parents and their children ages 8-12 with a BMI of ≥85th percentile are being recruited. The primary outcome is child BMI; secondary outcomes are child's diet and physical activity at baseline and 6- and 12-months post-baseline. Cost-effectiveness of the two interventions also will be examined. CONCLUSION: This is the first randomized controlled trial to examine use of a centrally located telephonic coaching service to support families of children with overweight and obesity in making AAP-recommended lifestyle changes. If effective, the Fitline program will provide an innovative model for widespread dissemination, setting new standards for weight management care in pediatric practice. TRIAL REGISTRATION: The ClinicalTrials.gov registration number is NCT03143660.