Comparing accuracy of tomosynthesis plus digital mammography or synthetic 2D mammography in breast cancer screening: baseline results of the MAITA RCT consortium.

AIM: The analyses here reported aim to compare the screening performance of digital tomosynthesis (DBT) versus mammography (DM). METHODS: MAITA is a consortium of four Italian trials, REtomo, Proteus, Impeto, and MAITA trial. The trials adopted a two-arm randomised design comparing DBT plus DM (REtomo and Proteus) or synthetic-2D (Impeto and MAITA trial) versus DM; multiple vendors were included. Women aged 45 to 69 years were individually randomised to one round of DBT or DM. FINDINGS: From March 2014 to February 2022, 50,856 and 63,295 women were randomised to the DBT and DM arm, respectively. In the DBT arm, 6656 women were screened with DBT plus synthetic-2D. Recall was higher in the DBT arm (5·84% versus 4·96%), with differences between centres. With DBT, 0·8/1000 (95% CI 0·3 to 1·3) more women received surgical treatment for a benign lesion. The detection rate was 51% higher with DBT, ie. 2·6/1000 (95% CI 1·7 to 3·6) more cancers detected, with a similar relative increase for invasive cancers and ductal carcinoma in situ. The results were similar below and over the age of 50, at first and subsequent rounds, and with DBT plus DM and DBT plus synthetic-2D. No learning curve was appreciable. Detection of cancers >= 20 mm, with 2 or more positive lymph nodes, grade III, HER2-positive, or triple-negative was similar in the two arms. INTERPRETATION: Results from MAITA confirm that DBT is superior to DM for the detection of cancers, with a possible increase in recall rate. DBT performance in screening should be assessed locally while waiting for long-term follow-up results on the impact of advanced cancer incidence.

EUSOMA quality indicators for non-metastatic breast cancer: An update.

INTRODUCTION: Quality care in breast cancer is higher if patients are treated in a Breast Center with a dedicated and specialized multidisciplinary team. Quality control is an essential activity to ensure quality care, which has to be based on the monitoring of specific quality indicators. Eusoma has proceeded with the up-dating of the 2017 Quality indicators for non-metastatic breast cancer based on the new diagnostic, locoregional and systemic treatment modalities. METHODS: To proceed with the updating, EUSOMA setup a multidisciplinary working group of BC experts and patients' representatives. It is a comprehensive set of QIs for early breast cancer care, which are classified as mandatory, recommended, or observational. For the first time patient reported outcomes (PROMs) have been included. As used in the 2017 EUSOMA QIs, evidence levels were based on the short version of the US Agency for Healthcare Research and Quality. RESULTS: This is a set of quality indicators representative for the different steps of the patient pathway in non-metastatic setting, which allow Breast Centres to monitor their performance with referring standards, i.e minimum standard and target. CONCLUSIONS: Monitoring these Quality Indicators, within the Eusoma datacentre will allow to have a state of the art picture at European Breast Centres level and the development of challenging research projects.

Trends and variation in treatment of early breast cancer in European certified breast centres: an EUSOMA-based analysis.

BACKGROUND: Practice indicators (PI) measure provided care making use of real-world data. This study describes trends and variations in adjuvant treatment of early breast cancer (EBC) using the European Society of Breast Cancer Specialists (EUSOMA) database. METHODS: The analysis was conducted on anonymous cumulative data registered by 56 certified breast centres, which all entered at least 500 new diagnoses in the database in the 10-year period 2010-2019. Practice trends of radiotherapy, endocrine treatment, chemotherapy, and anti-HER2 therapy were evaluated. The association with age group (<50, 50-69, ≥70) and geographical area of the centre (Northern, Central, Southern Europe; NE, CE, SE) was assessed with the Pearson Chi2 test for independence in contingency tables. RESULTS: In total, 150,150 patients with EBC were selected. Overall, radiotherapy was administered more frequently in NE centres, and conversely, endocrine, chemo-, and anti-HER2 therapy were used more frequently in SE centres (p<0.001). 46.9% of the pN1 patients received postmastectomy radiotherapy, with significant differences by age and geographical region (p < 0.001). Adjuvant endocrine treatment for endocrine-sensitive carcinoma in situ was administered in 46.1%, with a decreasing trend during the study period (58.5-34.5%; p < 0.001). Anti-HER2 therapy was delivered in 75.6% of all patients with HER2BC T1a/bN0, patients older than 70 received anti-HER2 in 67.6% in SE compared to 31.3% in NE centres. CONCLUSION: Important variations in EBC management between European certified breast centres have been demonstrated. PI using real-world data can help to monitor, evaluate, and eventually guide and align good clinical practice in the management of breast cancer.

European Society of Breast Cancer Specialists/Advanced Breast Cancer Global Alliance quality indicators for metastatic breast cancer care.

AIMS: Improvement in the care of patients with metastatic breast cancer (MBC) can only occur if the adequate quality of care is implemented and verified, including access to multidisciplinary, specialised care given in accordance with high-quality guidelines. To this purpose, European Society of Breast Cancer Specialists and the Advanced Breast Cancer Global Alliance joined efforts to develop the first set of quality indicators (QI) specifically for MBC that should be routinely measured and evaluated to ensure that breast cancer centres meet the required standards. METHODS: A working group of multidisciplinary European experts in breast cancer met to discuss each identified QI, reporting the definition, the minimum and target standard for breast cancer centres to achieve, and the motivation for selection. The level of evidence was determined according to the short version of the United States Agency for Healthcare Research and Quality classification. RESULTS: QI to measure access to and involvement in multidisciplinary and supportive care, appropriate pathological characterisation of disease, systemic therapies and radiotherapy were developed with the consensus of the working group. CONCLUSIONS: This is the first effort of a multistep project that aims to have QI for MBC routinely measured and evaluated to ensure that breast cancer centres achieve mandated standards in the care of patients with metastatic disease.

Overcoming barriers: Modelling the effect of potential future changes of organized breast cancer screening in Italy.

OBJECTIVES: Organized breast cancer screening may not achieve its full potential due to organizational and cultural barriers. In Italy, two identified barriers were low attendance in Southern Italy and, in Italy as a whole, underscreening and overscreening in parts of the eligible population. The objective of this study was to identify potential changes to overcome these barriers and to quantify their costs and effects. METHODS: To assess the impact of potential measures to improve breast cancer screening in Italy, we performed an evaluation of costs and effects for increasing adherence for Southern Italy and harmonizing screening intervals (biennial screening) for the whole of Italy, using an online tool (EU-TOPIA evaluation tool) based on the MIcrosimulation SCreening ANalysis (MISCAN) model. RESULTS: Increasing adherence in Southern Italy through investing in mobile screening units has an acceptable cost-effectiveness ratio of €9531 per quality-adjusted life year gained. Harmonizing the screening interval by investing in measures to reduce opportunistic screening and simultaneously investing in mobile screening units to reduce underscreening is predicted to gain 1% fewer life-years, while saving 19% of total screening costs compared to the current situation. CONCLUSIONS: Increasing adherence in Southern Italy and harmonizing the screening interval could result in substantial improvements at acceptable costs, or in the same benefits at lower costs. This example illustrates a systematic approach that can be easily applied to other European countries, as the online tools can be used by stakeholders to quantify effects and costs of a broad range of specific barriers, and ways to overcome them.

The impact of the SARS-COV-2 pandemic on the quality of breast cancer care in EUSOMA-certified breast centres.

AIMS: We analysed the impact of the SARS-CoV-2 pandemic (COVID-19) on the quality of breast cancer care in certified EUSOMA (European Society of Breast Cancer Specialists) breast centres. MATERIALS AND METHODS: The results of the EUSOMA quality indicators were compared, based on pseudonymised individual records, for the periods 1 March 2020 till 30 June 2020 (first COVID-19 peak in most countries in Europe) and 1 March 2019 till 30 June 2019. In addition, a questionnaire was sent to the participating Centres for investigating the impact of the COVID-19 pandemic on the organisation and the quality of breast cancer care. RESULTS: Forty-five centres provided data and 31 (67%) responded to the questionnaire. The total number of new cases dropped by 19% and there was a small significant higher tumour (p = 0.003) and lymph node (p = 0.011) stage at presentation. Comparing quality indicators (12,736 patients) by multivariable analysis showed mostly non-significant differences. Surgery could be performed in a COVID-free zone in 94% of the centres, COVID testing was performed before surgery in 96% of the centres, and surgical case load was reduced in 55% of the centres. Modifications of the indications for neoadjuvant endocrine therapy, chemotherapy, and targeted therapy were necessary in 23%, 23%, and 10% of the centres; changes in indications for adjuvant endocrine, chemo-, targeted, immune, and radiotherapy in 3%, 19%, 3%, 6%, and 10%, respectively. CONCLUSION: Quality of breast cancer care was well maintained in EUSOMA breast centres during the first wave of the COVID-19 pandemic. A small but significantly higher tumour and lymph node stage at presentation was observed.

Highly specialized Breast Centers did not experience delay of care during COVID-19 pandemic in Italy: the Senonetwork experience.

AIM OF THE STUDY: The study aims to evaluate the performance of selected, high-volume, highly specialized, Italian Breast Centers at the time of COVID-19 pandemic (year 2020), compared to pre-pandemic time (year 2019), highlighting differences in terms of clinical presentation of breast cancer (BC) and therapeutic strategies. METHODS: Patients' data were provided by the Senonetwork data warehouse Senonet. In order to examine changes in the surgical and oncological management of BC patients during different phases of COVID-19 pandemic, we took advantage of a selection quality indicators (QIs). We performed the analyses in two time-frames, from July to September (Jul-Sep) (2019 versus 2020) and from October to December (Oct-Dec) (2019 versus 2020). RESULTS: Our analysis did not show any statistically significant difference in terms of diagnosis, surgical, oncological and radiation therapy procedures between the two trimesters 2019 and 2020. Nevertheless, we observed statistically significant differences, favoring 2020, when analyzing time-to surgery and time-to radiotherapy. On the other hand, we observed a significant reduction of neoadjuvant chemotherapy and we did not recollect any data on a major use of neoadjuvant endocrine therapy. CONCLUSIONS: In Italian Breast Centers, partners of Senonetwork, we could not observe any treatment delay or change in standard clinical practice for BC care during the 2020 pandemic year, compared to 2019 pre-pandemic year. This finding is in contrast with the globally reported decrease in the performance of the Italian Breast Centers due to the COVID-19 pandemic, and has to be linked to the sharp selection of Senonetwork Breast Centers.

A randomised controlled trial of digital breast tomosynthesis vs digital mammography as primary screening tests: Screening results over subsequent episodes of the Proteus Donna study.

Proteus Donna is a randomised controlled trial aimed at prospectively evaluating screening with digital breast tomosynthesis (DBT), including interval cancer detection (ICD) and cancer detection (CD) in the analysis as a cumulative measure over subsequent screening episodes. Consenting women aged 46 to 68 attending the regional Breast Screening Service were randomly assigned to conventional digital mammography (DM, control arm) or DBT in addition to DM (DBT, study arm). At the subsequent round all participants underwent DM. Thirty-six months follow-up allowed for the identification of cancers detected in the subsequent screening and interscreening interval. Relative risk (RR) and 95% confidence interval (95% CI) were computed. Cumulative CD and Nelson-Aalen incidence were analysed over the follow-up period. Between 31 December 2014 and 31 December 2017, 43 022 women were randomised to DM and 30 844 to DBT. At baseline, CD was significantly higher (RR: 1.44, 95% CI: 1.21-1.71) in the study arm. ICD did not differ significantly between the two arms (RR: 0.92, 95% CI: 0.62-1.35). At subsequent screening with DM, the CD was lower (nearly significant) in the study arm (RR: 0.83, 95% CI: 0.65-1.06). Over the follow-up period, the cumulative CD (comprehensive of ICD) was slightly higher in the study arm (RR: 1.15, 95% CI: 1.01-1.31). The Nelson-Aalen cumulative incidence over time remained significantly higher in the study arm for approximately 24 months. Benign lesions detection was higher in the study arm at baseline and lower at subsequent tests. Outcomes are consistent with a lead time gain of DBT compared to DM, with an increase in false positives and moderate overdiagnosis.

Early assessment of the first wave of the COVID-19 pandemic on cancer screening services: The International Cancer Screening Network COVID-19 survey.

Screening can decrease the burden of breast, cervical, and colorectal cancers. The COVID-19 pandemic led many countries to suspend cancer screening services as part of their response to the pandemic. The International Cancer Screening Network (ICSN) carried out an online survey to assess the effects of the first wave of the COVID-19 pandemic on cancer screening. A 33-item survey was distributed to 834 email addresses to gather information about settings and assess decision-making processes that led to cancer screening suspension. Information about communication, impact on resources, and patient follow-up was collected. Quantitative data was analyzed as frequencies overall and by setting, while a comment section under each survey item captured nuanced details. Responses were recategorized into 66 settings, representing 35 countries. Most settings suspended cancer screening services (n = 60, 90.9%) in March 2020 (n = 45, 68.2%), guided by a government decision (n = 51, 77.3%). Few settings made the decision whether to suspend services based on a preparedness plan (n = 17, 25.8%). In most settings, professionals were reassigned (n = 41, 62.1%) and infrastructure repurposed (n = 35, 53.0%). The first wave of the COVID-19 pandemic has had profound effects on cancer screening worldwide, including the suspension of services in almost all settings. Most settings were unprepared to deal with the scale of the pandemic but demonstrated flexibility in the response. These results contribute to inform, through experiences and lessons learned, the next steps for the global cancer screening community to further evaluate the impact of COVID-19 and prepare for future disruptions.

Updated recommendations regarding the management of older patients with breast cancer: a joint paper from the European Society of Breast Cancer Specialists (EUSOMA) and the International Society of Geriatric Oncology (SIOG).

Breast cancer is increasingly prevalent in older adults and is a substantial part of routine oncology practice. However, management of breast cancer in this population is challenging because the disease is highly heterogeneous and there is insufficient evidence specific to older adults. Decision making should not be driven by age alone but should involve geriatric assessments plus careful consideration of life expectancy, competing risks of mortality, and patient preferences. A multidisciplinary taskforce, including members of the European Society of Breast Cancer Specialists and International Society of Geriatric Oncology, gathered to expand and update the previous 2012 evidence-based recommendations for the management of breast cancer in older individuals with the endorsement of the European Cancer Organisation. These guidelines were expanded to include chemotherapy toxicity prediction calculators, cultural and social considerations, surveillance imaging, genetic screening, gene expression profiles, neoadjuvant systemic treatment options, bone-modifying drugs, targeted therapies, and supportive care. Recommendations on geriatric assessment, ductal carcinoma in situ, screening, primary endocrine therapy, surgery, radiotherapy, adjuvant systemic therapy, and secondary breast cancer were updated.

Effect Modifiers of Low-Dose Tamoxifen in a Randomized Trial in Breast Noninvasive Disease.

PURPOSE: Low-dose tamoxifen halved recurrence after surgery in a phase III trial in breast noninvasive disease without increasing adverse events. We explored the effect of low-dose tamoxifen in clinically relevant subgroups, including menopausal status, estradiol levels, smoking, body mass index, and proliferation of baseline lesion. PATIENTS AND METHODS: Incidence of invasive breast cancer or ductal carcinoma in situ was the primary endpoint. HRs and interaction terms were estimated using Cox models. RESULTS: A favorable HR and 95% confidence interval (CI) could be demonstrated for postmenopausal status (HR = 0.30; 95% CI, 0.11-0.82 vs. HR = 0.73; 95% CI, 0.30-1.76 in premenopausal women; P interaction = 0.13), women with estradiol less than 15.8 pg/mL, presence of menopausal symptoms at baseline, and never smoking (P interaction = 0.07), although the interaction P value was >0.05 for all characteristics. Efficacy was similar in all body mass index categories. Tumors with Ki-67 above the median level of 10% had a greater benefit (HR = 0.27; 95% CI, 0.09-0.81) than those with Ki-67 ≤10% (HR = 1.58; 95% CI, 0.45-5.60; P interaction = 0.04). CONCLUSIONS: The efficacy of low-dose tamoxifen seems to be greater in postmenopausal women and in women with lower estradiol levels. Benefits appear to be larger also in women with menopausal symptoms, never smokers, and tumors with Ki-67 >10%. Our results by menopausal status provide important insight into low-dose tamoxifen personalized treatment, although caution is necessary given their exploratory nature. Observation of an improved response in tumors with Ki-67 >10% is consistent but the use of the marker in this setting is investigational.See related commentary by Fabian, p. 3510.

Monitoring and evaluation of breast cancer screening programmes: selecting candidate performance indicators.

BACKGROUND: In the scope of the European Commission Initiative on Breast Cancer (ECIBC) the Monitoring and Evaluation (M&E) subgroup was tasked to identify breast cancer screening programme (BCSP) performance indicators, including their acceptable and desirable levels, which are associated with breast cancer (BC) mortality. This paper documents the methodology used for the indicator selection. METHODS: The indicators were identified through a multi-stage process. First, a scoping review was conducted to identify existing performance indicators. Second, building on existing frameworks for making well-informed health care choices, a specific conceptual framework was developed to guide the indicator selection. Third, two group exercises including a rating and ranking survey were conducted for indicator selection using pre-determined criteria, such as: relevance, measurability, accurateness, ethics and understandability. The selected indicators were mapped onto a BC screening pathway developed by the M&E subgroup to illustrate the steps of BC screening common to all EU countries. RESULTS: A total of 96 indicators were identified from an initial list of 1325 indicators. After removing redundant and irrelevant indicators and adding those missing, 39 candidate indicators underwent the rating and ranking exercise. Based on the results, the M&E subgroup selected 13 indicators: screening coverage, participation rate, recall rate, breast cancer detection rate, invasive breast cancer detection rate, cancers > 20 mm, cancers ≤10 mm, lymph node status, interval cancer rate, episode sensitivity, time interval between screening and first treatment, benign open surgical biopsy rate, and mastectomy rate. CONCLUSION: This systematic approach led to the identification of 13 BCSP candidate performance indicators to be further evaluated for their association with BC mortality.

Performance indicators in breast cancer screening in the European Union: A comparison across countries of screen positivity and detection rates.

Comparable performance indicators for breast cancer screening in the European Union (EU) have not been previously reported. We estimated adjusted breast cancer screening positivity rate (PR) and detection rates (DR) to investigate variation across EU countries. For the age 50-69 years, the adjusted EU-pooled PR for initial screening was 8.9% (cross-programme variation range 3.2-19.5%) while DR of invasive cancers was 5.3/1,000 (range 3.8-7.4/1,000) and DR of ductal carcinoma in situ (DCIS) was 1.3/1,000 (range 0.7-2.7/1,000). For subsequent screening, the adjusted EU-pooled PR was 3.6% (range 1.4-8.4%), the DR was 4.0/1,000 (range 2.2-5.8/1,000) and 0.8/1,000 (range 0.5-1.3/1,000) for invasive and DCIS, respectively. Adjusted performance indicators showed remarkable heterogeneity, likely due to different background breast cancer risk and awareness between target populations, and also different screening protocols and organisation. Periodic reporting of the screening indicators permits comparison and evaluation of the screening activities between and within countries aiming to improve the quality and the outcomes of screening programmes. Cancer Screening Registries would be a milestone in this direction and EU Screening Reports provide a fundamental contribution to building them.

The requirements of a specialist breast centre.

This article is an update of the requirements of a specialist breast centre, produced by EUSOMA and endorsed by ECCO as part of Essential Requirements for Quality Cancer Care (ERQCC) programme, and ESMO. To meet aspirations for comprehensive cancer control, healthcare organisations must consider the requirements in this article, paying particular attention to multidisciplinarity and patient-centred pathways from diagnosis, to treatment, to survivorship.

Role of Magnetic Resonance Imaging in the Evaluation of Breast Cancer Response to Neoadjuvant Chemotherapy.

BACKGROUND/AIM: The aim of the study was to evaluate whether residual tumor assessment by magnetic resonance imaging (MRI) after neoadjuvant chemotherapy (NACT) is fundamental for a successive surgical strategy. PATIENTS AND METHODS: We collected 55 MRIs performed after NACT. RESULTS: Pathological response rate was 20%. MRI's sensitivity, specificity, PPV and NPV were 50%, 88%, 54% and 86%, respectively. We observed a high variability between the different subgroups, with high number of false positives in luminal A/B tumors. Triple negative and HER2+ tumors had almost the same specificity and sensitivity (81% and 50%). Nevertheless, in the HER2+ group, PPV was greater than that in the triple negative group (71% and 33% respectively) and the NPV of the triple negative group was greater than that of the HER2+ one (90% and 64%, respectively). Statistical analysis showed a weak but significant correlation between MRI and pathological assessment of residual tumor dimension. CONCLUSION: The present study, confirms literature data about MRI accuracy in diagnosing HER2+ and triple negative tumors, but suggests caution in case of luminal tumors' evaluation.

Evidence for reducing cancer-specific mortality due to screening for breast cancer in Europe: A systematic review.

BACKGROUND: The aim of this study was to quantify the impact of organised mammography screening on breast cancer mortality across European regions. Therefore, a systematic review was performed including different types of studies from all European regions and stringently used clearly defined quality appraisal to summarise the best evidence. METHODS: Six databases were searched including Embase, Medline and Web of Science from inception to March 2018. To identify all eligible studies which assessed the effect of organised screening on breast cancer mortality, two reviewers independently applied predefined inclusion and exclusion criteria. Original studies in English with a minimum follow-up of five years that were randomised controlled trials (RCTs) or observational studies were included. The Cochrane risk of bias instrument and the Newcastle-Ottawa Scale were used to assess the risk of bias. RESULTS: Of the 5015 references initially retrieved, 60 were included in the final analysis. Those comprised 36 cohort studies, 17 case-control studies and 7 RCTs. None were from Eastern Europe. The quality of the included studies varied: Nineteen of these studies were of very good or good quality. Of those, the reduction in breast cancer mortality in attenders versus non-attenders ranged between 33% and 43% (Northern Europe), 43%-45% (Southern Europe) and 12%-58% (Western Europe). The estimates ranged between 4% and 31% in invited versus non-invited. CONCLUSION: This systematic review provides evidence that organised screening reduces breast cancer mortality in all European regions where screening was implemented and monitored, while quantification is still lacking for Eastern Europe. The wide range of estimates indicates large differences in the evaluation designs between studies, rather than in the effectiveness of screening.

Key issues that need to be considered while revising the current annex of the European Council Recommendation (2003) on cancer screening.

The 2003 European Council recommendation urging the Member States to introduce or scale up breast, cervical and colorectal cancer screening through an organized population-based approach has had a remarkable impact. We argue that the recommendation needs to be updated for at least two sets of reasons. First, some of the current clinical guidelines include new tests or protocols that were not available at the time of the Council document. Some have already been adopted by organized screening programs, such as newly defined age ranges for mammography screening, Human Papillomavirus (HPV)-based cervical cancer screening, fecal immunochemical test (FIT) and sigmoidoscopy for colorectal cancer screening. Second, the outcomes of randomized trials evaluating screening for lung and prostate cancer have been published recently and the balance between harms and benefits needs to be pragmatically assessed. In the European Union, research collaboration and networking to exchange and develop best practices should be regularly supported by the European Commission. Integration between primary and secondary preventive strategies through comprehensive approaches is necessary not only to maximize the reduction in cancer burden but also to control the rising trend of other noncommunicable diseases sharing the same risk factors.

Low-grade screen-detected ductal carcinoma in situ progresses more slowly than high-grade lesions: evidence from an international multi-centre study.

PURPOSE: Nuclear grade is an important indicator of the biological behaviour of ductal carcinoma in situ (DCIS). De-escalation of treatment has been suggested for low-grade DCIS. Our aim is to estimate the relative rate of progression of DCIS by nuclear grade by analysing the distribution of nuclear grade by detection at initial or subsequent screening. METHODS: We asked International Cancer Screening Network sites to complete, based on their screening and clinical databases, an aggregated data file on DCIS detection, diagnosis and treatment. RESULTS: Eleven screening programs reported 5068 screen-detected pure DCIS in nearly 7 million screening tests in women 50-69 years of age. For all programs combined, low-grade DCIS were 20.1% (range 11.4-31.8%) of graded DCIS, intermediate grade 31.0% and high grade 48.9%. Detection rates decreased more steeply from initial to subsequent screening in low compared to high-grade DCIS: the ratios of subsequent to initial detection rates were 0.39 for low grade, 0.51 for intermediate grade, and 0.75 for high grade (p < 0.001). CONCLUSIONS: These results suggest that the duration of the preclinical detectable phase is longer for low than for high-grade DCIS. The findings from this large multi-centre, international study emphasize that the management of low-grade DCIS should be carefully scrutinized in order to minimize overtreatment of screen-detected slow-growing or indolent lesions. The high variation by site in the proportion of low grade suggests that further pathology standardization and training would be beneficial.