Comparisons of assessment pathways after abnormal mammography screening in Denmark, Norway, and Spain.

PURPOSE: To ensure high-quality screening programmes and effective utilization of resources, it is important to monitor how cancer detection is affected by different strategies performed at recall assessment. This study aimed to describe procedures performed at recall assessment and compare and evaluate the performance of the assessment in Denmark, Norway, and Spain in terms of screen-detected cancer (SDC) and interval cancer (IC) rates. METHODS: We included women aged 50-69 years from Denmark, Norway, and Spain, who were recalled for assessment after screening mammography, and recorded all procedures performed during six months after diagnosis, and the timing of the procedures. Women were followed for two years and screen-detected and interval cancer, and sensitivity of recall was calculated and compared. RESULTS: In total, data from 24,645 Danish, 30,050 Norwegian, and 41,809 Spanish women were included in the study. Most of the women had some assessment within 2 months in all three countries. SDC rates were higher in Denmark (0.57) and Norway (0.60) compared to Spain (0.38), as were the IC rates, i.e. 0.25 and 0.18 vs. 0.12, respectively. The sensitivity of the diagnostic follow-up was somewhat higher in Denmark (98.3%) and Norway (98.2%), compared to Spain (95.4%), but when excluding non-invasive assessment pathways, the sensitivities were comparable. CONCLUSION: This comparison study showed variation in the assessment procedures used in the three countries as well as the SDC and IC rates and the sensitivity of recall.

Personalized Breast Cancer Screening: A Risk Prediction Model Based on Women Attending BreastScreen Norway.

BACKGROUND: We aimed to develop and validate a model predicting breast cancer risk for women targeted by breast cancer screening. METHOD: This retrospective cohort study included 57,411 women screened at least once in BreastScreen Norway during the period from 2007 to 2019. The prediction model included information about age, mammographic density, family history of breast cancer, body mass index, age at menarche, alcohol consumption, exercise, pregnancy, hormone replacement therapy, and benign breast disease. We calculated a 4-year absolute breast cancer risk estimates for women and in risk groups by quartiles. The Bootstrap resampling method was used for internal validation of the model (E/O ratio). The area under the curve (AUC) was estimated with a 95% confidence interval (CI). RESULTS: The 4-year predicted risk of breast cancer ranged from 0.22-7.33%, while 95% of the population had a risk of 0.55-2.31%. The thresholds for the quartiles of the risk groups, with 25% of the population in each group, were 0.82%, 1.10%, and 1.47%. Overall, the model slightly overestimated the risk with an E/O ratio of 1.10 (95% CI: 1.09-1.11) and the AUC was 62.6% (95% CI: 60.5-65.0%). CONCLUSIONS: This 4-year risk prediction model showed differences in the risk of breast cancer, supporting personalized screening for breast cancer in women aged 50-69 years.

Use of chronic medications and risk of severe death due to COVID-19 in hospitalised patients.

OBJECTIVES: To evaluate the potential association between chronic exposure to medication and death related to COVID-19. METHODS: This is a retrospective cross-sectional study that included all patients hospitalised due to COVID-19 from 11 March to 4 June 2020 in our centre. Chronic patient medication was classified by the Anatomical Therapeutic Chemical (ATC) classification; demographic and clinical data were analysed. Multivariate logistic regression models were used to estimate the adjusted odds ratios (aOR) of death for each drug exposure; each aOR represents an independent model adjusted by clinical factors related to COVID-19 mortality. RESULTS: The study included 978 patients with a mean (SD) age of 64.5 (17.7) years who were predominantly male (531, 54.3%). Of all 978 patients, 182 (18.61%) died during the follow-up of the study. The most common Charlson Comorbidity Index (CCI) was 0, 4.2% were smokers, 16.7% were obese, 47.4% had hypertension, and 19.4% were diabetic. Most patients (70.8%) were prescribed at least one treatment, 32.5% used >5 treatments, and 8.6% >10. Our data suggest that COVID-19 hospitalised patients taking trimethoprim and analogues, leukotriene receptor antagonists, calcineurin inhibitors, aldosterone antagonists, selective immunosuppressants, propulsives, insulins and analogues, and benzodiazepine derivatives have a higher risk of death. CONCLUSIONS: This study investigated the association between chronic exposure to drugs and the risk of death in COVID-19 patients. Our results have shed some light on the impact of chronic drug exposure on the risk of severe COVID-19; however, further research is needed to increase the understanding about its relevance.

Impact of the COVID-19 pandemic on breast cancer screening indicators in a Spanish population-based program: a cohort study.

Background: To assess the effect of the COVID-19 pandemic on performance indicators in the population-based breast cancer screening program of Parc de Salut Mar (PSMAR), Barcelona, Spain. Methods: We conducted a before-and-after, study to evaluate participation, recall, false positives, the cancer detection rate, and cancer characteristics in our screening population from March 2020 to March 2021 compared with the four previous rounds (2012-2019). Using multilevel logistic regression models, we estimated the adjusted odds ratios (aORs) of each of the performance indicators for the COVID-19 period, controlling by type of screening (prevalent or incident), socioeconomic index, family history of breast cancer, and menopausal status. We analyzed 144,779 invitations from 47,571women. Results: During the COVID-19 period, the odds of participation were lower in first-time invitees (aOR = 0.90 [95% CI = 0.84-0.96]) and in those who had previously participated regularly and irregularly (aOR = 0.63 [95% CI = 0.59-0.67] and aOR = 0.95 [95% CI = 0.86-1.05], respectively). Participation showed a modest increase in women not attending any of the previous rounds (aOR = 1.10 [95% CI = 1.01-1.20]). The recall rate decreased in both prevalent and incident screening (aOR = 0.74 [95% CI = 0.56-0.99] and aOR = 0.80 [95% CI = 0.68-0.95], respectively). False positives also decreased in both groups (prevalent aOR = 0.92 [95% CI = 0.66-1.28] and incident aOR = 0.72 [95% CI = 0.59-0.88]). No significant differences were observed in compliance with recall (OR = 1.26, 95% CI = 0.76-2.23), cancer detection rate (aOR = 0.91 [95% CI = 0.69-1.18]), or cancer stages. Conclusions: The COVID-19 pandemic negatively affected screening attendance, especially in previous participants and newcomers. We found a reduction in recall and false positives and no marked differences in cancer detection, indicating the robustness of the program. There is a need for further evaluations of interval cancers and potential diagnostic delays. Funding: This study has received funding by grants PI19/00007 and PI21/00058, funded by Instituto de Salud Carlos III (ISCIII) and cofunded by the European Union and Grant RD21/0016/0020 funded by Instituto de Salud Carlos III and by the European Union NextGenerationEU, Mecanismo para la Recuperación y la Resiliencia (MRR).

Comparison of technical parameters and women's experience between self-compression and standard compression modes in mammography screening: a single-blind randomized clinical trial.

OBJECTIVES: We compared the compression force, breast thickness, and glandular dose, as well as the severity of discomfort and women's experience between the patient-assisted compression (PAC) and standard compression (SC) modes. MATERIALS AND METHODS: We conducted a prospective randomized controlled study at Hospital del Mar in Barcelona, Spain. We included 448 asymptomatic women aged 50 to 69 years old, attending their screening round from December 2017 to December 2019. Mammograms included the two bilateral views. In each woman, one breast was studied with SC and the other with PAC. The mode used in each breast was selected following a randomized list. Compression force, breast thickness, and average glandular dose were obtained for each of the 1792 images. We also recorded the degree of discomfort and women's experience, after mammogram acquisitions, using a predefined survey. RESULTS: Higher compression forces were obtained with PAC than with SC (99.27 N vs 83.25 N, p < 0.001). Breast thickness mode (56.11 mm vs 57.52 mm, p = 0.015) and glandular dose (1.34 mGy vs 1.37 mGy, p = 0.018) were lower in PAC. The discomfort score was slightly higher with PAC (mean 3.94 vs 3.69, p = 0.042), but in the satisfaction survey, more women reported that PAC caused less discomfort. Additionally, 63.2% of women (289/448) preferred PAC. CONCLUSION: PAC achieved higher compression forces without impairing the other technical imaging parameters and enhanced women's experience of screening mammography. We believe there were no clinically significant differences in the severity of discomfort between the two modes. KEY POINTS: • Self-compression allows higher compression forces than the standard compression mode. • Self-compression does not affect technical imaging parameters. • Self-compression improved women's experience of screening mammography when standard compression was used on one breast and self-compression on the other.

Does the patient-assisted compression mode affect the mammography quality? A within-woman randomized controlled trial.

OBJECTIVES: Evaluate the image quality of a mammography screening device using the patient-assisted compression (PAC) compared with the standard compression (SC) mode. METHODS: This prospective within-woman, randomized controlled trial was conducted between September 2017 and December 2019. Participants were asymptomatic women aged 50 to 69 years attending their second or subsequent screening mammography round. By random assignment, one breast underwent the SC and the other breast, the PAC. Image quality was evaluated as perfect, good, moderate, or inadequate (PGMI) on 10 criteria for the craniocaudal (CC) view and 8 criteria for the mediolateral oblique (MLO) view. Pearson's chi-square test, with Yates' correction if pertinent, was performed to compare image quality between compression modes. RESULTS: A total of 444 participants were included (mean [± standard deviation] age, 60 [± 4.9] years). There were no differences in the percentages of PGMI between the PAC and SC modes for the CC view (perfect, 37% [162/444] vs 37% [163/444]; good, 1% [5/444] vs 2% [9/444]; moderate, 62% [277/444] vs 61% [271/444]; inadequate, 0% vs 0.2% [1/444]; p = .88) or for the MLO view (perfect, 53% [237/444] vs 56% [247/444]; good, 22% [99/444] vs 22% [97/444]; moderate, 23% [102/444] vs 22% [98/444]; inadequate, 1% [6/444] vs 0.5% [2/444]; p = .72). No differences were found when we stratified by laterality or when analyzed by PGMI criteria. CONCLUSION: PAC does not seem to impair mammographic image quality. Future research should focus in a daily practice setting. KEY POINTS: No differences were found in the distribution of the PGMI classification, a tool for quality assessment, between patient-assisted compression and standard compression. Similar results were found on stratification of image quality by mammographic view and breast laterality for both types of compression. None of the PGMI criteria had significantly more errors in patient-assisted compression than in standard compression.

Impact of Detection Mode in a Large Cohort of Women Taking Part in a Breast Screening Program.

Objective: The aim of this study was to evaluate the existing survival rate and clinical-pathological differences among patients with breast cancer detected by mammographic screening. Materials and Methods: This multicenter cohort study examined 1,248 patients who took part in a national screening program for the early detection of breast cancer over an eight-year period. Results: Of the two patient subgroups (interval and screening), we found significant differences in the distribution of prognostic factors, with interval cases presenting at a lower mean age (p = 0.002), with higher percentages of human epidermal growth factor receptor 2 (HER-2) or triple negative and lower percentages of luminal A or luminal B carcinomas (p = 0.001), advanced stages (p<0.001), lower hormone receptor expression (p<0.001), poorer differentiation (p<0.001) and lower survival (p<0.001). Among the screening group, patients with tumors detected during the first screening round had a significantly lower mean age (p<0.001), a lower frequency of comorbidities (p = 0.038) and a lower tendency (p<0.1) to be diagnosed as triple negative breast carcinomas than incident cases. Conclusion: Our results highlight that breast tumors detected during the first screening round are frequently characterized by a more benign phenotype than the rest of the screening subgroups, which could be of help when stratifying the risk of death and selecting the best treatment option for each patient.

Impact of COVID-19 on Hospital Admissions and Healthcare Quality Indicators in Non-COVID Patients: A Retrospective Study of the First COVID-19 Year in a University Hospital in Spain.

Few studies have assessed the impact of the COVID-19 pandemic on non-COVID diseases and healthcare quality. We aimed to evaluate changes in rates of hospitalisations, complications, in-hospital mortality, and readmissions among patients with non-COVID diseases during a one-year period after the pandemic onset. From March 2018 to February 2021 a retrospective observational study of hospital admissions in a university hospital in Spain was conducted. Non-COVID hospitalisations admitted through the emergency department were compared between the pre-COVID period (n = 28,622) and the COVID period (n = 11,904). We assessed rate ratios (RaR), comparing the weekly number of admissions and risk ratios (RR) to examine rates of complications, in-hospital mortality, readmissions, and severity. Statistical significance was set at p < 0.05. The weekly admission rate dropped by 20.8% during the complete lockdown. We observed significant reductions in admissions related to diseases of the respiratory system and circulatory system. Admissions for endocrine and metabolic diseases increased. The complication rates increased (RR = 1.21, 95% CI: 1.05;1.4), while in-hospital mortality rates held steady during the COVID period (RR = 1.09, 95% CI: 0.98;1.2). Hospital efforts to maintain quality and safety standards despite disruptions translated into a moderate increase in complications but not in in-hospital mortality. Reduced hospitalisations for conditions requiring timely treatment may have significant public health consequences.

Long-Term Risk of Breast Cancer after Diagnosis of Benign Breast Disease by Screening Mammography.

Assessing the long-term risk of breast cancer after diagnosis of benign breast disease by mammography is of utmost importance to design personalised screening strategies. We analysed individual-level data from 778,306 women aged 50-69 years with at least one mammographic screening participation in any of ten breast cancer screening centers in Spain from 1996 to 2015, and followed-up until 2017. We used Poisson regression to compare the rates of incident breast cancer among women with and without benign breast disease. During a median follow-up of 7.6 years, 11,708 (1.5%) women had an incident of breast cancer and 17,827 (2.3%) had a benign breast disease. The risk of breast cancer was 1.77 times higher among women with benign breast disease than among those without (95% CI: 1.61 to 1.95). The relative risk increased to 1.99 among women followed for less than four years, and remained elevated for two decades, with relative risk 1.96 (95% CI: 1.32 to 2.92) for those followed from 12 to 20 years. Benign breast disease is a long-term risk factor for breast cancer. Women with benign breast disease could benefit from closer surveillance and personalized screening strategies.

Adherence of long-term breast cancer survivors to follow-up care guidelines: a study based on real-world data from the SURBCAN cohort.

PURPOSE: To identify adherence to follow-up recommendations in long-term breast cancer survivors (LTBCS) of the SURBCAN cohort and to identify its determinants, using real-world data. METHODS: We conducted a retrospective study using electronic health records from 2012 to 2016 of women diagnosed with incident breast cancer in Spain between 2000 and 2006 and surviving at least 5 years. Adherence to basic follow-up recommendations, adherence according to risk of recurrence, and overall adherence were calculated based on attendance at medical appointments and imaging surveillance, by year of survivorship. Logistic regression models were fitted to depict the association between adherence and its determinants. RESULTS: A total of 2079 LTBCS were followed up for a median of 4.97 years. Of them, 23.6% had survived ≥ 10 years at baseline. We estimated that 79.5% of LTBCS were overall adherent to at least one visit and one imaging test. Adherence to recommendations decreased over time and no differences were found according to recurrence risk. Determinants of better overall adherence were diagnosis in middle age (50-69 years old), living in a more-deprived area, having fewer years of survival, receiving primary treatment, and being alive at the end of follow-up. CONCLUSION: We identified women apparently not complying with surveillance visits and tests. Special attention should be paid to the youngest and eldest women at diagnosis and to those with longer survival.

Mammographic features of benign breast lesions and risk of subsequent breast cancer in women attending breast cancer screening.

OBJECTIVES: To evaluate the mammographic features in women with benign breast disease (BBD) and the risk of subsequent breast cancer according to their mammographic findings. METHODS: We analyzed data from a Spanish cohort of women screened from 1995 to 2015 and followed up until December 2017 (median follow-up, 5.9 years). We included 10,650 women who had both histologically confirmed BBD and mammographic findings. We evaluated proliferative and nonproliferative BBD subtypes, and their mammographic features: architectural distortion, asymmetries, calcifications, masses, and multiple findings. The adjusted hazard ratios (aHR) and 95% confidence intervals (95% CI) for breast cancer were estimated using a Cox proportional hazards model. We plotted the adjusted cumulative incidence curves. RESULTS: Calcifications were more frequent in proliferative disease with atypia (43.9%) than without atypia (36.8%) or nonproliferative disease (22.2%; p value < 0.05). Masses were more frequent in nonproliferative lesions (59.1%) than in proliferative lesions without atypia (35.1%) or with atypia (30.0%; p value < 0.05). Multiple findings and architectural distortion were more likely in proliferative disease (16.1% and 4.7%) than in nonproliferative disease (12.8% and 1.9%). Subsequent breast cancer occurred in 268 (2.5%) women. Compared with women who had masses, the highest risk of subsequent breast cancer was found in those with architectural distortions (aHR, 2.21; 95% CI, 1.16-4.22), followed by those with multiple findings (aHR, 1.89; 95% CI, 1.34-2.66), asymmetries (aHR, 1.66; 95% CI, 0.84-3.28), and calcifications (aHR, 1.60; 95% CI, 1.21-2.12). CONCLUSION: BBD subtypes showed distinct mammographic findings. The risk of subsequent breast cancer was high in those who have shown architectural distortion, multiple findings, asymmetries, and calcifications than in women with masses. KEY POINTS: • The presence of mammographic findings in women attending breast cancer screening helps clinicians to assess women with benign breast disease (BBD). • Calcifications were frequent in BBDs with atypia, which are the ones with a high breast cancer risk, while masses were common in low-risk BBDs. • The excess risk of subsequent breast cancer in women with BBD was higher in those who showed architectural distortion compared to those with masses.

Use of health services among long-term breast cancer survivors in Spain: longitudinal study based on real-world data.

PURPOSE: This study aimed to evaluate health service utilization in Spain among long-term breast cancer survivors and to compare it with that among women with no history of breast cancer. METHODS: Study based on the SURBCAN cohort includes a sample of long-term breast cancer survivors and a sample of women without breast cancer from 5 Spanish regions. Healthcare utilization was assessed through primary care, hospital visits, and tests during the follow-up period (2012 to 2016) by using electronic health records. Annual contact rates to healthcare services were calculated, and crude and multivariate count models were fitted to estimate the adjusted relative risk of healthcare services use. RESULTS: Data were obtained from 19,328 women, including 6512 long-term breast cancer survivors. Healthcare use was higher among breast cancer survivors (20.9 vs 16.6; p < 0.0001) and decreased from >10 years of survival. Breast cancer survivors who underwent a mastectomy were more likely to have a primary care visit (RR = 3.10 95% CI 3.08-3.11). Five to ten years survivors were more likely to have hospital inpatient visits and imaging test compared to women without breast cancer (RRa = 1.35 95% CI 1.30-1.39 and RRa = 1.27 95% CI 1.25-1.29 respectively). CONCLUSION: This study shows higher use of health services in long-term breast cancer survivors than in women without breast cancer regardless of survival time. IMPLICATIONS FOR CANCER SURVIVORS: These results help to estimate the health resources needed for the growing group of breast cancer survivors and to identify risk factors that drive higher use of health services.

Developing and validating an individualized breast cancer risk prediction model for women attending breast cancer screening.

BACKGROUND: Several studies have proposed personalized strategies based on women's individual breast cancer risk to improve the effectiveness of breast cancer screening. We designed and internally validated an individualized risk prediction model for women eligible for mammography screening. METHODS: Retrospective cohort study of 121,969 women aged 50 to 69 years, screened at the long-standing population-based screening program in Spain between 1995 and 2015 and followed up until 2017. We used partly conditional Cox proportional hazards regression to estimate the adjusted hazard ratios (aHR) and individual risks for age, family history of breast cancer, previous benign breast disease, and previous mammographic features. We internally validated our model with the expected-to-observed ratio and the area under the receiver operating characteristic curve. RESULTS: During a mean follow-up of 7.5 years, 2,058 women were diagnosed with breast cancer. All three risk factors were strongly associated with breast cancer risk, with the highest risk being found among women with family history of breast cancer (aHR: 1.67), a proliferative benign breast disease (aHR: 3.02) and previous calcifications (aHR: 2.52). The model was well calibrated overall (expected-to-observed ratio ranging from 0.99 at 2 years to 1.02 at 20 years) but slightly overestimated the risk in women with proliferative benign breast disease. The area under the receiver operating characteristic curve ranged from 58.7% to 64.7%, depending of the time horizon selected. CONCLUSIONS: We developed a risk prediction model to estimate the short- and long-term risk of breast cancer in women eligible for mammography screening using information routinely reported at screening participation. The model could help to guiding individualized screening strategies aimed at improving the risk-benefit balance of mammography screening programs.

Breast density, benign breast disease, and risk of breast cancer over time.

OBJECTIVES: Assessing the combined effect of mammographic density and benign breast disease is of utmost importance to design personalized screening strategies. METHODS: We analyzed individual-level data from 294,943 women aged 50-69 years with at least one mammographic screening participation in any of four areas of the Spanish Breast Cancer Screening Program from 1995 to 2015, and followed up until 2017. We used partly conditional Cox models to assess the association between benign breast disease, breast density, and the risk of breast cancer. RESULTS: During a median follow-up of 8.0 years, 3697 (1.25%) women had a breast cancer diagnosis and 5941 (2.01%) had a benign breast disease. More than half of screened women had scattered fibroglandular density (55.0%). The risk of breast cancer independently increased with the presence of benign breast disease and with the increase in breast density (p for interaction = 0.84). Women with benign breast disease and extremely dense breasts had a threefold elevated risk of breast cancer compared with those with scattered fibroglandular density and without benign breast disease (hazard ratio [HR] = 3.07; 95%CI = 2.01-4.68). Heterogeneous density and benign breast disease was associated with nearly a 2.5 elevated risk (HR = 2.48; 95%CI = 1.66-3.70). Those with extremely dense breast without a benign breast disease had a 2.27 increased risk (95%CI = 2.07-2.49). CONCLUSIONS: Women with benign breast disease had an elevated risk for over 15 years independently of their breast density category. Women with benign breast disease and dense breasts are at high risk for future breast cancer. KEY POINTS: • Benign breast disease and breast density were independently associated with breast cancer. • Women with benign breast disease had an elevated risk for up to 15 years independently of their mammographic density category.

Risk of breast cancer two years after a benign biopsy depends on the mammographic feature prompting recall.

OBJECTIVE: We aimed to explore whether the type of mammographic feature prompting a false-positive recall (FPR) during mammography screening influences the risk and timing of breast cancer diagnosis, particularly if assessed with invasive procedures. STUDY DESIGN: We included information on women screened and recalled for further assessment in Spain between 1994 and 2015, with follow-up until 2017, categorizing FPRs by the assessment (noninvasive or invasive) and mammographic feature prompting the recall. MAIN OUTCOME MEASURES: Breast cancer rates in the first two years after FPR (first period) and after two years (second period). RESULTS: The study included 99,825 women with FPRs. In both periods, the breast cancer rate was higher in the invasive assessment group than in the noninvasive group (first period 12 ‰ vs 1.9 ‰, p < 0.001; second period 4.4‰ vs 3.1‰, p < 0.001). During the first period, the invasive assessment group showed diverse breast cancer rates for each type of mammographic feature, with a higher rate for asymmetric density (31.9‰). When the second period was compared with the first, the breast cancer rate decreased in the invasive assessment group (from 12‰ to 4.4‰, p < 0.001) and increased in the noninvasive assessment group (from 1.9‰ to 3.1‰, p < 0.001). CONCLUSION: In the context of mammography screening, the risk of breast cancer diagnosis during the first two years after FPR was particularly high for women undergoing invasive assessment; importantly, the risk was modified by type of mammographic feature prompting the recall. This information could help to individualize follow-up after exclusion of malignancy.

Differences in breast cancer risk after benign breast disease by type of screening diagnosis.

INTRODUCTION: We aimed to assess differences in breast cancer risk across benign breast disease diagnosed at prevalent or incident screens. MATERIALS AND METHODS: We conducted a retrospective cohort study with data from 629,087 women participating in a long-standing population-based breast cancer screening program in Spain. Each benign breast disease was classified as non-proliferative, proliferative without atypia, or proliferative with atypia, and whether it was diagnosed in a prevalent or incident screen. We used partly conditional Cox hazard regression to estimate the adjusted hazard ratios of the risk of breast cancer. RESULTS: Compared with women without benign breast disease, the risk of breast cancer was significantly higher (p-value = 0.005) in women with benign breast disease diagnosed in an incident screen (aHR, 2.67; 95%CI: 2.24-3.19) than in those with benign breast disease diagnosed in a prevalent screen (aHR, 1.87; 95%CI: 1.57-2.24). The highest risk was found in women with a proliferative benign breast disease with atypia (aHR, 4.35; 95%CI: 2.09-9.08, and 3.35; 95%CI: 1.51-7.40 for those diagnosed at incident and prevalent screens, respectively), while the lowest was found in women with non-proliferative benign breast disease (aHR, 2.39; 95%CI: 1.95-2.93, and 1.63; 95%CI: 1.32-2.02 for those diagnosed at incident and prevalent screens, respectively). CONCLUSION: Our study showed that the risk of breast cancer conferred by a benign breast disease differed according to type of screen (prevalent or incident). To our knowledge, this is the first study to analyse the impact of the screening type on benign breast disease prognosis.

Exploring the Role of Breast Density on Cancer Prognosis among Women Attending Population-Based Screening Programmes.

BACKGROUND: Our aim was to assess the role of breast density on breast cancer mortality and recurrences, considering patient and tumour characteristics and the treatments received among women attending population-based screening programmes. METHODS: We conducted a retrospective cohort study among women aged 50-69 years attending population-based screening programmes, diagnosed with invasive breast cancer between 2000 and 2009, and followed up to 2014. Breast density was categorised as low density (≤25% dense tissue), intermediate density (25-50%), and high density (≥50%). Cox proportional hazards regression models were fitted to estimate the adjusted hazard ratios (aHR) and 95% confidence intervals (95% CI) for death and recurrences, adjusting by patient characteristics, mode of detection (screen-detected vs. interval cancer), and tumour features. RESULTS: The percentage of deaths and recurrences was higher among women with intermediate- and high-density breasts than among women with low-density breasts (p=0.011 for death; p=0.037 for recurrences). Adjusted Cox proportional hazards regression models revealed that women with intermediate- and high-density breasts had a higher risk of death than women with low-density breasts, being statistically significant for intermediate densities (aHR = 2.19 [95% CI: 1.16-4.13], aHR = 1.44 [95% CI: 0.67-3.1], respectively). No association was found between breast density and recurrences. CONCLUSIONS: Breast density was associated with a higher risk of death, but not of recurrences, among women participating in breast cancer screening. These findings reinforce the need to improve screening sensitivity among women with dense breasts and to routinely assess breast density, not only for its role as a risk factor for breast cancer but also for its potential influence on cancer prognosis.

Personalized breast cancer screening strategies: A systematic review and quality assessment.

BACKGROUND: The effectiveness of breast cancer screening is still under debate. Our objective was to systematically review studies assessing personalized breast cancer screening strategies based on women's individual risk and to conduct a risk of bias assessment. METHODS: We followed the standard methods of The Cochrane Collaboration and PRISMA declaration and searched the MEDLINE, EMBASE and Clinical Trials databases for studies published in English. The quality of the studies was assessed using the ISPOR-AMCP-NPC Questionnaire and The Cochrane Risk of Bias Tool. Two independent reviewers screened full texts and evaluated the risk of bias. RESULTS: Out of the 1533 initially retrieved citations, we included 13 studies. Three studies were randomized controlled trials, while nine were mathematical modeling studies, and one was an observational pilot study. The trials are in the recruitment phase and have not yet reported their results. All three trials used breast density and age to define risk groups, and two of them included family history, previous biopsies, and genetic information. Among the mathematical modeling studies, the main risk factors used to define risk groups were breast density, age, family history, and previous biopsies. Six studies used genetic information to define risk groups. The most common outcome measures were the gain in quality-adjusted life years (QALY), absolute costs, and incremental cost-effectiveness ratio (ICER), while the main outcome in the observational study was the detection rate. In all models, personalized screening strategies were shown to be effective. The randomized trials were of good quality. The modeling studies showed moderate risk of bias but there was wide variability across studies. The observational study showed a low risk of bias but its utility was moderate due to its pilot design and its relatively small scale. CONCLUSIONS: There is some evidence of the effectiveness of screening personalization in terms of QUALYs and ICER from the modeling studies and the observational study. However, evidence is lacking on feasibility and acceptance by the target population. REVIEW REGISTRATION: PROSPERO: CRD42018110483.