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Background: Abemaciclib-induced diarrhea is a relevant concern in clinical practice. Postbiotics have emerged as a promising option for managing it., Materials and Methods: We conducted a retrospective-prospective, 2-group, observational study to assess the impact of the postbiotic PostbiotiX-Restore, derived by Lactobacillus paracasei CNCM I-5220, on abemaciclib-induced diarrhea in patients with hormone receptor-positive HER2-negative breast cancer. The prospective population (Postbio group) received postbiotic during the first cycle of abemaciclib, while the retrospective one received standard care (Standard group). Diarrhea grading was defined according to the National Cancer Institute's Common Terminology Criteria for Adverse Events., Results: During the first cycle, diarrhea occurred in 78.9% of patients in the Standard cohort and 97.1% in the Postbio one, with most cases being G1-G2. Severe (G3) diarrhea was significantly less frequent in the Postbio group (0%) compared to the Standard one (7.9%; P = .029). Over the entire study period, while the grading difference was not statistically significant, G3 events were less frequent in the Postbio population (5.9%) than the Standard one (15.4%). Moreover, Postbio patients required fewer dose reductions due to diarrhea compared to the Standard group (P = .002). Notably, in the Postbio population, G1 and G2 events had short median durations (3 and 1 days, respectively) and, for the 2 patients experiencing G3 events during the second abemaciclib cycle (off postbiotic), diarrhea lasted only 1 day., Conclusions: Our study demonstrates the effect of PostbiotiX-Restore in mitigating abemaciclib-induced diarrhea, resulting in reduced severity, fewer dose reductions, and shorter duration. Further exploration and validation in larger cohorts are needed., (© The Author(s) 2024. Published by Oxford University Press.)

Purpose: This study quantifies the impact on budget and cost per health benefit of implementing digital breast tomosynthesis (DBT) in place of digital mammography (DM) for breast cancer screening among asymptomatic women in Italy., Methods: A budget impact analysis and a cost consequence analysis were conducted using parameters from the MAITA project and literature. The study considered four scenarios for DBT implementation, i.e., DBT for all women, DBT for women aged 45-49 years, DBT based on breast density (BI-RADS C + D or D only), and compared these to the current DM screening. Healthcare provider's perspective was adopted, including screening, diagnosis, and cancer treatment costs., Results: Introducing DBT for all women would increase overall screening costs by 20%. Targeting DBT to women aged 45-49 years or with dense breasts would result in smaller cost increases (3.2% for age-based and 1.4-10.7% for density-based scenarios). The cost per avoided interval cancer was significantly higher when DBT was applied to all women compared to targeted approaches. The cost per gained early-detected cancer slightly increases in targeted approaches, while the assumptions on the clinical significance and overdiagnosis of cancers detected by DBT and not by DM have a strong impact., Conclusions: Implementing DBT as a primary breast cancer test in screening programs in Italy would lead to a substantial increase in costs. Tailoring DBT use to women aged 45-49 or with dense breasts could enhance the feasibility and sustainability of the intervention. Further research is needed to clarify the impact of DBT on overdiagnosis and the long-term outcomes., (© 2024. Italian Society of Medical Radiology.)

Purpose: We present a comprehensive investigation into the organizational, social, and ethical impact of implementing digital breast tomosynthesis (DBT) as a primary test for breast cancer screening in Italy. The analyses aimed to assess the feasibility of DBT specifically for all women aged 45-74, women aged 45-49 only, or those with dense breasts only., Methods: Questions were framed according to the European Network of Health Technology Assessment (EuNetHTA) Screening Core Model to produce evidence for the resources, equity, acceptability, and feasibility domains of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) decision framework. The study integrated evidence from the literature, the MAITA DBT trials, and Italian pilot programs. Structured interviews, surveys, and systematic reviews were conducted to gather data on organizational impact, acceptability among women, reading and acquisition times, and the technical requirements of DBT in screening., Results: Implementing DBT could significantly affect the screening program, primarily due to increased reading times and the need for additional human resources (radiologists and radiographers). Participation rates in DBT screening were similar, if not better, to those observed with standard digital mammography, indicating good acceptability among women. The study also highlighted the necessity for specific training for radiographers. The interviewed key persons unanimously considered feasible tailored screening strategies based on breast density or age, but they require effective communication with the target population., Conclusions: An increase in radiologists' and radiographers' workload limits the feasibility of DBT screening. Tailored screening strategies may maximize the benefits of DBT while mitigating potential challenges., (© 2024. Italian Society of Medical Radiology.)

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., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Paolo Giorgi Rossi reports financial support was provided by Italian Ministry of Health. Pierpaolo Pattacini reports was provided by Emilia-Romagna Regional Health Authority. Antonio Ponti reports financial support was provided by Piedmont Region (Department of Health). Antonio Ponti reports financial support was provided by foundation Edo Tempia (a non-profit organisation). Antonio Ponti reports equipment, drugs, or supplies was provided by Regional Consortium for Informative Systems (CSI). Antonio Ponti reports financial support was provided by University of Turin. Paola Mantellini reports financial support was provided by Tuscany Region. Pierpaolo Pattacini reports equipment, drugs, or supplies and travel were provided by GE Healthcare. Antonio Ponti reports equipment, drugs, or supplies was provided by im3D S.p.A Torino. Stephen Duffy has received indirect funding in the past from Hologic Inc. Valentina Iotti, Andrea Nitrosi reports travel was provided by GE Healthcare. Pierpaolo Pattacini, Valentina Iotti, Andrea Nitrosi, Francesco Sardanelli reports a relationship with GE Healthcare that includes: speaking and lecture fees. Valentina Iotti reports a relationship with Bayer that includes: speaking and lecture fees. Paolo Giorgi Rossi, Livia Giordano, Stephen Duffy, and Francesco Sardanelli are members of the European Commission Initiative on Breast Cancer working groups. They contributed to the development of new breast cancer screening recommendations and quality assurance scheme. Livia Giordano is past president of the Gruppo Italiano Screening Mammografico, the Italian scientific society on breast cancer screening. All remaining authors have declared no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

We investigated whether we could identify a panel of miRNAs associated with response to treatment in tumor tissues of patients with Hormone Receptor-positive/HER2-negative metastatic breast cancer treated with endocrine therapy (ET) and the CDK4/6 inhibitor (CDK4/6i)i palbociclib. In total, 52 patients were evaluated, with 41 receiving treatment as the first line. The overall median PFS was 20.8 months (range 2.5-66.6). In total, 23% of patients experienced early progression (<6 months). Seven miRNAs ( miR-378e , miR-1233 , miR-99b-5p , miR-1260b , miR-448 , -miR-1252-5p , miR-324-3p , miR-1233-3p ) showed a statistically significant negative association with PFS. When we considered PFS < 6 months, miR-378e , miR-99b-5p , miR-877-5p , miR-1297 , miR-455-5p , and miR-4536-5p were statistically associated with a poor outcome. In the multivariate analysis, the first three miRNAs confirmed a significant and independent impact on PFS. The literature data and bioinformatic tools provide an underlying molecular rationale for most of these miRNAs, mainly involving the PI3K/AKT/mTOR pathway and cell-cycle machinery as cyclin D1, CDKN1B, and protein p27 Kip1 and autophagy. Our findings propose a novel panel of miRNAs associated with a higher likelihood of early progression in patients treated with ET and Palbociclib and may contribute to shed some light on the mechanisms of de novo resistance to CDK4/6i, but this should be considered exploratory and evaluated in larger cohorts.

This article aims to present the results of a national, cross-sectional, voluntary, online survey on the presence and roles of associations of breast cancer patients and volunteers in Italian specialist breast centres. The survey was developed according to standard methods. The questionnaire was pre-tested by a random sample of three breast centres, loaded onto the SurveyMonkey platform, and piloted by one volunteer breast centre. The breast centre clinical leads were invited to participate via email. A link to the online instrument was provided. No financial incentives were offered. The results were reported using standard descriptive statistics. The response rate was 82/128 (65%). Members of associations were routinely present in 70% Italian breast centres. Breast centres most often reporting their presence were those certified by the European Society of Breast Cancer Specialists. Patient support (reception and information, listening, identification of needs, and psychological support) was the primary area where associations were reported to offer services. The magnitude of this phenomenon warrants a study to investigate the impact of the activities of associations on the quality of life of patients and on the cost-benefit ratio of the service, and the modes of their interactions with the nursing staff and the medical staff.

Mammographic breast cancer screening is effective in reducing breast cancer mortality. Nevertheless, several limitations are known. Therefore, developing an alternative or complementary non-invasive tool capable of increasing the accuracy of the screening process is highly desirable. The objective of this study was to identify circulating microRNA (miRs) ratios associated with BC in women attending mammography screening. A nested case-control study was conducted within the ANDROMEDA cohort (women of age 46-67 attending BC screening). Pre-diagnostic plasma samples, information on life-styles and common BC risk factors were collected. Small-RNA sequencing was carried out on plasma samples from 65 cases and 66 controls. miR ratios associated with BC were selected by two-sample Wilcoxon test and lasso logistic regression. Subsequent assessment by RT-qPCR of the miRs contained in the selected miR ratios was carried out as a platform validation. To identify the most promising biomarkers, penalised logistic regression was further applied to candidate miR ratios alone, or in combination with non-molecular factors. Small-RNA sequencing yielded 20 candidate miR ratios associated with BC, which were further assessed by RT-qPCR. In the resulting model, penalised logistic regression selected seven miR ratios (miR-199a-3p&#95;let-7a-5p, miR-26b-5p&#95;miR-142-5p, let-7b-5p&#95;miR-19b-3p, miR-101-3p&#95;miR-19b-3p, miR-93-5p&#95;miR-19b-3p, let-7a-5p&#95;miR-22-3p and miR-21-5p&#95;miR-23a-3p), together with body mass index (BMI), menopausal status (MS), the interaction term BMI * MS, life-style score and breast density. The ROC AUC of the model was 0.79 with a sensitivity and specificity of 71.9% and 76.6%, respectively. We identified biomarkers potentially useful for BC screening measured through a widespread and low-cost technique. This is the first study reporting circulating miRs for BC detection in a screening setting. Validation in a wider sample is warranted.Trial registration: The Andromeda prospective cohort study protocol was retrospectively registered on 27-11-2015 (NCT02618538)., (© 2023. The Author(s).)

Purpose: Five-year data of the phase III trial TAM-01 showed that low-dose tamoxifen at 5 mg once daily administered for 3 years in women with intraepithelial neoplasia (IEN) reduced by 52% the recurrence of invasive breast cancer or ductal carcinoma in situ (DCIS), without additional adverse events over placebo. Here, we present the 10-year results., Methods: We randomly assigned 500 women with breast IEN (atypical ductal hyperplasia, lobular carcinoma in situ [LCIS], or hormone-sensitive or unknown DCIS) to low-dose tamoxifen or placebo after surgery with or without irradiation. The primary end point was the incidence of invasive breast cancer or DCIS., Results: The TAM-01 population included 500 women (20% atypical ductal hyperplasia, 11% LCIS, and 69% DCIS). The mean (±SD) age at the start of treatment was 54 ± 9 years, and 58% of participants were postmenopausal. After a median follow-up of 9.7 years (IQR, 8.3-10.9 years), 66 breast cancers (15 in situ; 51 invasive) were diagnosed: 25 in the tamoxifen group and 41 in the placebo group (annual rate per 1,000 person-years, 11.3 with tamoxifen v 19.5 with placebo; hazard ratio [HR], 0.58; 95% CI, 0.35 to 0.95; log-rank P = .03). Most recurrences were invasive (77%) and ipsilateral (59%). Regarding contralateral breast cancer incidence, there were six events in the tamoxifen arm and 16 in the placebo arm (HR, 0.36; 95% CI, 0.14 to 0.92; P = .025). The number needed to be treated to prevent one case of breast event with tamoxifen therapy was 22 in 5 years and 14 in 10 years. The benefit was seen across all patient subgroups. There was a significant 50% reduction of recurrence with tamoxifen in the DCIS cohort, which represents 70% of the overall population (HR, 0.50; 95% CI, 0.28 to 0.91; P = .02). No between-group difference in the incidence of serious adverse events was reported during the prolonged follow-up period., Conclusion: Tamoxifen 5 mg once daily for 3 years significantly prevents recurrence from noninvasive breast cancer after 7 years from treatment cessation without long-term adverse events.

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., (© 2022 UICC.)

Introduction: Performance indicators for organised breast cancer screening programmes in Italy, 2011-2019, were evaluated., Materials and Methods: Aggregated data were gathered by the National Centre for Screening Monitoring from over 150 regional or sub-regional screening programmes in Italy. Invitation and examination coverage, participation rate (PR), recall rate (RR), detection rate, positive predictive value (PPV) for the target population as a whole (women aged 50-69), by 5-year age-class, geographical macro-area (North, Centre, South-Islands with the exception of three Regions for missing/uncomplete data) and Region were estimated., Results: Coverage showed an increasing positive trend, especially in the South-Islands, and PR was stable all over Italy. On the other hand, an increasing RR and decreasing PPV were recorded, especially at the first screening test and in some regions., Discussion and Conclusions: The positive increase in coverage is accompanied by a worsening of some performance indicators for which a better resource allocation and staff training are required. For this reason, further and continuous monitoring is mandatory.

We retrospectively investigated in women treated with fulvestrant for HR+/HER2 negative advanced breast cancer clinical, pathological and molecular features associated with long-term benefit from treatment defined as being progression-free at 18 months. Specifically, we analyzed on formalin-fixed paraffin-embedded tumor samples ESR1 and PI3KCA mutations and miRNAs profiles. 59 patients were evaluable (median age of 67 years, range 32-92). 18-month PFS rate was 27%; the lack of visceral metastases significantly predicted the likelihood of being progression-free at 18 months, while PI3KCA mutations, found in 36% of patients, were not associated with 18-month PFS. As of miRNAs, miR-549a, miR-644a, miR-16-5p were negatively while let-7c-5p was positively associated with 18-month PFS. In addition, miR-520d-3p and miR-548g-3p values were significantly lower while miR-603, miR-181a-5p and miR-199a-miR-199b-3p values were significantly higher in patients achieving 18-month PFS. In silico analysis of targets modulated by these two latter groups of miRNAs show that in patients achieving 18-month PFS the Hippo and Wnt signaling pathways were predicted to be upregulated while endocrine resistance was potentially repressed by miR-603, miR-181a-5p and miR-199a-miR-199b-3p. Our results provide additional clues on the molecular mechanisms involved in fulvestrant activity and resistance. Underlying pathways should be further elucidated and confirmed in larger cohorts., (© 2022. The Author(s).)

Background: Despite recommendations, mammography screening is often insufficiently integrated into specialist breast centres. A national, cross-sectional, voluntary, online survey on this issue was carried out among the Italian breast centres associated with Senonetwork, the Italian network of breast cancer services., Methods: A 73-item questionnaire was created, pre-tested and piloted. Centres integrating and not integrating a screening programme were compared using the unified theory of acceptance and use of technology (UTAUT) model. Centres' clustering was performed using the Gower's distance metric. Groups and clusters were compared with the equality-of-means test., Results: The response rate was 82/128 (65%). Overall, 84% (69/82) breast centres reported a collaboration with a screening programme in performing and/or reading mammograms and in the diagnostic work-up of women with abnormal screening results. The same proportion was observed among those centres responding to all questions (62/74). Performance expectancies (or the perceived usefulness of integration in terms of clinical quality, patient convenience, ease of job, and professional growth), satisfaction and motivation were higher in those centres collaborating with the screening programme. Effort expectancy indicators (or the degree to which the respondents believe that the integration is easy to implement) and those concerning the existence of facilitating conditions were lower both in centres collaborating and not collaborating with the screening programme. Among the former, six clusters of centres, distributed from 'no integration' to 'high', were identified. In cluster analysis, the highest level of integration was associated with higher agreement that integration eases the job, offers better opportunities for professional growth, and makes the working environment more satisfactory. The least integrated cluster assigned the lowest score to the statement that local health authority made available the resources needed., Conclusions: While confirming the positive effects of integrating screening programmes into breast centres, this survey has brought to light specific difficulties that must be faced. The results provide insights into the importance of integration focusing on the perspectives of professional career and motivation. The deficiency of facilitating conditions to integration is modifiable. Screening professionals' societies may have a role as initiators of the integration. Other supporting actions may be included in health laws at the national and regional level., (© 2022. The Author(s).)

The decision aid "Donnainformata-mammografia" (https://www.donnainformata-mammografia.it/en/) has been developed with the aim of providing clear information on the benefits and harms of breast cancer screening, and the controversies on the relationship between mortality reduction and overdiagnosis. It was evaluated in a randomized clinical trial showing it increases informed choice and does not decrease participation in screening.This article describes the framework, the guiding principles, and the operational phases of the tool development.The project was developed within the national screening programme. The promoters decided to state their placement, to start from the information needs of women and what is already known, and to balance spontaneous navigation with "nudging" to key contents. Three focus groups with 18 women and 4 interviews were organized. Participants expressed a favourable attitude towards screening, and no knowledge of the debate on screening efficacy and overdiagnosis. A literature review and a comparison of decision aids were conducted. The online tool included the results of these steps. The home page presents key information with links to relevant topics, so that the person can decide to stop there having an overview or to continue. The «ready to decide» button, which leads to the section of decision support, can be clicked on every page. Here, the person can evaluate a list of key points on the basis of her values, in order to decide to participate in screening or not.

Background: Few data are available about real-life cardiotoxicity associated with s.c. versus i.v. trastuzumab treatment of early-stage, HER2-positive breast cancer, and little is known about its predisposing factors., Patients and Methods: We retrospectively reviewed data of 363 adult patients treated with adjuvant trastuzumab for HER2-positive breast cancer. Univariate statistical analysis was performed, and a multivariable logistic model was developed to identify independent risk factors of cardiac toxicity., Results: Within 5 years, the overall incidence of events meeting our criteria was 11.8%, and an early discontinuation of trastuzumab was recorded in 20 patients (5.5%). No cases of congestive heart failure occurred, neither multiple events per patient were observed. A total of 184 patients received i.v. and 179 received s.c. trastuzumab. Compared with the s.c. formulation, a higher cardiotoxicity rate for the i.v. administration (15.2% vs 8.4%) was found, and particularly in those patients with cardiovascular risk factors (19.3% vs 8.7%), at the univariate and multivariate analyses. Although more patients with prior anthracycline-based chemotherapy experienced cardiac events, the association of this therapy with cardiac events was not significant. The incidence of cardiac events was not influenced by anthropometric data (e.g. body mass index) or a diagnosis of diabetes mellitus. 5-year event-free survival was 91.7% in the overall population; event-free survival rates were similar between the s.c. and the i.v. groups., Conclusion: Our study shows a more favorable safety profile of s.c. versus i.v trastuzumab administration. The use of s.c. trastuzumab could be advisable in at-risk patients., Competing Interests: Declaration of competing interest Armando Santoro has received honoraria from BMS, AstraZeneca, MSD, Lilly, Bayer, Takeda, Roche, Mundipharma, Novartis, Servier, Amgen, ArQule, Celgene, Incyte, AbbVie, Gilead, Pfizer, Daiichi, Sandoz, and Sanofi. Rita De Sanctis has received honoraria form EISAI, Kyowa Kirin and Novartis. The other authors have no funding and conflicts of interests to disclose., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Into blood relatives of patients affected by breast cancer, the prevalence of pancreatic ductal adenocarcinoma (PDAC) seems to be elevated. BRCA1/2 mutations as other VUS (variants of uncertain significance) could be responsible., Methods: We retrospectively revised dataset of Pancreatic Surgery Unit of Humanitas Clinical and Research Center - IRCCS and identified patients who underwent resection for PDAC between 2010 and 2018. We evaluated neoplastic family history and remote pathological history, particularly for breast and prostate tumors. The characteristics of family history were described. Overall survival (OS) and progression free survival (PFS) were calculated for different identified groups., Results: 483 PDAC have been analyzed; 57% had a family history positive for neoplasia; 25% at least showed a blood relative affected by one of these type of cancers: PDAC, breast and prostate, of which 88% was a first degree relative (FDR). One hundred and six patients (22%) had a previous neoplasia, of which 8% a breast cancer and 4% a prostate one. Into this group of patients, 54% had a family history positive for neoplasia and 23% consisted of either a pancreatic neoplasm, or breast tumor or prostate cancer; 71% was a FDR. With a median follow-up of 54.9 months (range 0.066-120), the median survival was 22,8 months. Both OS than PFS weren't statistically significant, considering family history and remote pathological history., Conclusions: There appears to be a high prevalence of breast and prostate cancer in family members and patients with PDAC. PDAC patients have the prognosis of the pancreatic cancer, not influenced by a previous treated neoplasia.

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., (© 2020 UICC.)

Background: Improving the quality of information and communication is a priority in organised breast cancer screening and an ethical duty. Programmes must offer the information each woman is looking for, promoting informed decision-making. This study aimed to develop and evaluate a web-based dynamic decision aid (DA)., Methods: A pragmatic randomised trial carried out in six regional organised screening programmes recruited women at the first invitation receiving DA or a web-based standard brochure (SB). The primary outcome was informed choice measured on knowledge, attitudes, and intentions. Follow-up period: 7-10 days. Secondary outcomes included participation rate, satisfaction, decisional conflict, and acceptability of DA., Results: Two thousand one hundred and nineteen women were randomised and 1001 completed the study. Respectively, 43.9% and 36.9% in the DA and SB reached the informed choice. The DA gave a 13-point higher proportion of women aware about overdiagnosis compared to SB (38.3% versus 25.2%, p < 0.0001). The percentage of women attending screening was the same: 84% versus 83%. Decisional conflict was significantly lower in the DA group (14.4%) than in the SB group (19.3%)., Conclusion: DA increases informed choice. Complete information including the pros, cons, controversies, and overdiagnosis-overtreatment issues boost a woman's knowledge without reducing the rate of actual screening participation., Clinical Trial Registration: ClinicalTrials.gov number NCT03097653.

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.

Background: Because the risk of relapse of node-negative breast cancer (BC) is varying, we evaluated the prognosis of patients with this disease and the factors associated with increased risk of relapse., Patients and Methods: The clinical charts of patients with BC with evidence of negative nodes and with a potential ≥ 5-year follow-up were retrospectively reviewed., Results: We analyzed 1276 patients. Over a median follow-up of 71.6 months (range, 1-227.2 months), we observed 159 events of relapse or death. The median RFS was 170 months. The median overall survival (OS) was 192 months. At univariate analysis, older age, negative hormonal receptors, larger tumor size and higher proliferation index (Ki67) were associated with worse recurrence-free survival (RFS) and OS (P < .05); higher grading was associated with worse RFS (P = .01). At multivariate analysis for RFS, age, Ki67 and tumor size confirmed their independent prognostic role. At multivariate analysis for OS, age and positive hormonal receptors showed an independent prognostic role. We observed no differences in prognosis between human epidermal growth factor receptor 2 (HER2) positive and triple-negative (TN) BC, but TNBC showed a worse OS compared with luminal-like BC., Conclusions: In node-negative BC, age, hormone receptor status, tumor size and Ki67 were prognostic factors. The TNBC subtype was not associated with poorer prognosis compared with the HER2-positive subtype, but showed a worse OS compared with luminal-like BC., (Copyright © 2020. Published by Elsevier Inc.)

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., (© 2020 International Agency for Research on Cancer (IARC/WHO); licensed by UICC.)

Objectives: to evaluate the incidence of advanced-stage breast cancer (BC) - an early surrogate indicator of effectiveness of mammography screening - among women who attended the Friuli Venezia Giulia (FVG) Region (Northern Italy) screening programme compared to women who did not attend., Design: retrospective cohort study. Women invited to the first screening round (2006-2007) were identified from the database of the programme. The cohort was record-linked to the archive of women invited to the second round (2008-2009). The definition of attendance to screening was based on attendance to at least one of the two rounds. The incidence of BC was assessed through record linkage with the FVG cancer registry using an anonymous univocal identifier (end of follow-up: 31st December 2013). Three distinct definitions of advanced stage were used: pT2 or greater (pT2+), positive lymph nodes (pN+), and TNM stage II or greater (stage II+)., Setting and Participants: organized mammography screening programme for women aged 50-69 years in the five regional healthcare districts., Main Outcome Measures: incidence rate ratio (IRR) between attenders and non-attenders, adjusted for age and deprivation index, with 95% confidence interval (95%CI)., Results: the cohort included 104,488 attenders and 49,839 non-attenders. During follow-up (median duration 84 months), 2,717 invasive BCs were diagnosed among attenders and 1,149 among non-attenders. Total incidence rate was 13% higher among attenders (IRR 1.13; 95%CI 1.05-1.21). These, conversely, had a 36% lower rate of pT2+ BC (IRR 0.64; 95%CI 0.56-0.72), a 13% lower rate of pN+ BC (IRR 0.87; 95%CI 0.78-0.98), a 22% lower rate of stage II+ BC (IRR 0.78; 95%CI 0.70-0.87), and a 32% lower rate of mastectomy (IRR 0.68; 95%CI 0.60-0.78)., Conclusions: attenders had lower incidence rates of advanced-stage BC. This early effect is suggestive of a future impact of the screening programme on BC mortality.

Aim: Trastuzumab prolongs progression-free and overall survival in HER2+ breast cancer (BC), but these are associated with increased distant recurrences and central nervous system metastases (CNSm). We retrospectively evaluated outcome and prognostic factors in CNSm and non-CNSm patients. Methods: Records of HER2+ BC treated in 2000-2017 were reviewed. Results: 283/1171 (24%) HER2+ BC patients developed metastatic disease. 109/283 patients (39%) have CNSm associated with worse prognosis and increased risk of death (hazard ratio: 4.7; 95% CI: 3.5-6.4). Prognostic factors were: number of CNSm (single vs multiple lesions; 3-year overall survival 39 vs 18%; p = 0.003); brain radiation (30 vs 14%; p < 0.001); new HER2-targeting therapies (30.6 vs 22.5%; p = 0.025). Conclusion: Prognosis of BC patients with CNSm has improved using HER2-targeting therapies but remains poor.

Description: The European Commission Initiative for Breast Cancer Screening and Diagnosis guidelines (European Breast Guidelines) are coordinated by the European Commission's Joint Research Centre. The target audience for the guidelines includes women, health professionals, and policymakers., Methods: An international guideline panel of 28 multidisciplinary members, including patients, developed questions and corresponding recommendations that were informed by systematic reviews of the evidence conducted between March 2016 and December 2018. GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence to Decision frameworks were used to structure the process and minimize the influence of competing interests by enhancing transparency. Questions and recommendations, expressed as strong or conditional, focused on outcomes that matter to women and provided a rating of the certainty of evidence., Recommendations: This synopsis of the European Breast Guidelines provides recommendations regarding organized screening programs for women aged 40 to 75 years who are at average risk. The recommendations address digital mammography screening and the addition of hand-held ultrasonography, automated breast ultrasonography, or magnetic resonance imaging compared with mammography alone. The recommendations also discuss the frequency of screening and inform decision making for women at average risk who are recalled for suspicious lesions or who have high breast density.

Neither breast cancer prevention and early-detection programs, nor their outcomes, are uniform across Europe. This article describes the rationale, methods, and process for development of the European Commission (EC) Initiative on Breast Cancer Screening and Diagnosis Guidelines. To be consistent with standards set by the Institute of Medicine and others, the EC followed 6 general principles. First, the EC selected, via an open call, a panel with broad representation of areas of expertise. Second, it ensured that all recommendations were supported by systematic reviews. Third, the EC separately considered important subgroups of women, included patient advocates in the guidelines development group, and focused on good communication to inform women's decisions. Fourth, EC rules on conflicts of interest were followed and the GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence to Decision frameworks were used to structure the process and minimize the influence of competing interests. Fifth, it focused its recommendations on outcomes that matter to women, and certainty of the evidence is rated for each. Sixth, the EC elicited stakeholder feedback to ensure that the recommendations remain up to date and relevant to practice. This article describes the approach and highlights ways of disseminating and adapting the recommendations both within and outside Europe, using innovative information technology tools.

Objectives: Available evidence on axillary surgery has accumulated dramatically in the last two decades in favor of less invasive care. The aim of this paper is to study 16-years trends in the surgical management of the axilla in a large population-based data set of screen-detected breast cancers in Italy and to document at what extent recommendations have been adopted in actual clinical care., Material and Methods: This is a retrospective cohort study documenting the surgical management of the axilla in primary breast cancer patients over time. We retrieved from the Italian database of screen-detected cancers 41213 cases diagnosed in women aged 50-69 between years 2000 and 2015 in twelve Italian Regions., Results: In pN0 cases, an increasing trend (p < 0.001) in the number of patients who received sentinel lymph node biopsy (SLNB) as the only axillary staging procedure was observed. In pN + cases SLNB was the only staging procedure in an increasing number of patients (p < 0.001) especially since the publication of the ACOSOG-Z0011 paper. In ductal carcinoma in situ (DCIS) SLNB was more frequent in mastectomies and in high grade and large lesions. However, 45% of low grade, small DCIS over the whole time period had some form of axillary surgery., Conclusion: This large series of screen-detected cases documents a strong time trend in the direction of reducing axillary surgery and hence potential harms from treatment. The continuing practice of SLNB in low risk DCIS is of concern in an era of increasing awareness towards overdiagnosis and overtreatment., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

In Italy women aged 50-69 are invited for a population-based breast cancer (BC) screening. Physicians, policy makers and patient associations agree on the need to inform women about the benefits and harms in order to permit an informed decision. Decision aids (DA) are an effective way to support people in their decisions about health. This trial aims to assess women's informed choices, according to their health literacy and values, on participating or not in BC screening for the first time. Benefits, harms and controversies are presented. The contents of the DA were developed on the basis of: a) findings of three focus groups and four interviews, organized in the three Italian screening centers; b) analysis of the literature. A web-based platform (www.donnainformata-mammografia) was developed to implement the DA in a multilevel model. The impact of the DA will be evaluated in a randomized controlled trial with a one week follow-up. The women will be randomized to DA or a standard brochure via web. We will invite 8160 women to obtain the final sample size of 816 women. The primary outcome will be informed choice, measured via knowledge, attitudes and intentions on BC screening., Secondary Outcomes: participation rate and decisional conflict process. If the informed choice will be reached, the web DA will be open source and could be implemented in BC screenings. This model could be applied to other health care settings and cancer screenings.

Background: In recent years growing interest has been posed on alternative ways to screen women for breast cancer involving different imaging techniques or adjusting screening interval by breast cancer risk estimates. A new research area is studying circulating microRNAs as molecular biomarkers potentially useful for non invasive early detection together with the analysis of single-nucleotide polymorphisms (SNPs). The Andromeda study is a prospective cohort study on women attending breast cancer screening in a northern Italian area. The aims of the study are: 1) to define appropriate women risk-based stratifications for personalized screening considering different factors (reproductive, family and biopsy history, breast density, lifestyle habits); 2) to evaluate the diagnostic accuracy of selected circulating microRNAs in a case-control study nested within the above mentioned cohort., Methods: About 21,000 women aged 46-67 years compliant to screening mammography are expected to be enrolled. At enrolment, information on well-known breast cancer risk factors and life-styles habits are collected through self-admistered questionnaires. Information on breast density and anthropometric measurements (height, weight, body composition, and waist circumference) are recorded. In addition, women are requested to provide a blood sample for serum, plasma and buffy-coat storing for subsequent molecular analyses within the nested case-control study. This investigation will be performed on approximately 233 cases (screen-detected) and 699 matched controls to evaluate SNPs and circulating microRNAs. The whole study will last three years and the cohort will be followed up for ten years to observe the onset of new breast cancer cases., Discussion: Nowadays women undergo the same screening protocol, independently of their breast density and their individual risk to develop breast cancer. New criteria to better stratify women in risk groups could enable the screening strategies to target high-risk women while reducing interventions in those at low-risk. In this frame the present study will contribute in identifying the feasibility and impact of implementing personalized breast cancer screening., Trial Registration: NCT02618538 (retrospectively registered on 27-11-2015.).

This position paper, issued by ICBR/SIRM and GISMa, summarizes the evidence on DBT and provides recommendations for its use. In the screening setting, DBT in adjunct to digital mammography (DM) increased detection rate by 0.5-2.7‰ and decreased false positives by 0.8-3.6% compared to DM alone in observational and double-testing experimental studies. The reduction in recall rate could be less prominent in those screening programs which already have low recall rates with DM. The increase in radiation exposure associated with DM/DBT protocols has been solved by the introduction of synthetic mammograms (sDM) reconstructed from DBT datasets. Thus, whenever possible, sDM/DBT should be preferred to DM/DBT. However, before introducing DBT as a routine screening tool for average-risk women, we should wait for the results of randomized controlled trials and for a statistically significant and clinically relevant reduction in the interval cancer rate, hopefully associated with a reduction in the advanced cancer rate. Otherwise, a potential for overdiagnosis and overtreatment cannot be excluded. Studies exploring this issue are ongoing. Screening of women at intermediate risk should follow the same recommendations, with particular protocols for women with previous BC history. In high-risk women, if mammography is performed as an adjunct to MRI or in the case of MRI contraindications, sDM/DBT protocols are suggested. Evidence exists in favor of DBT usage in women with clinical symptoms/signs and asymptomatic women with screen-detected findings recalled for work-up. The possibility to perform needle biopsy or localization under DBT guidance should be offered when DBT-only findings need characterization or surgery.

Background: In Italy women aged 50-69 are invited for a population-based breast cancer (BC) screening. Physicians, policy makers and patients associations agree on the need to inform women about the benefits and harms in order to permit an informed decision. Decision aids (DA) are an effective way to support people in their decisions about health. This trial aims to assess women's informed choices, according to their health literacy and values, on participating or not in BC screening for the first time. Benefits, harms and controversies are presented., Methods/design: The impact of the DA will be evaluated in a randomized controlled trial with a two-week follow-up. Women will be randomized via web to DA or a standard brochure. We will invite 8160 women, to obtain a final sample of 816 women. The primary outcome will be informed choice, measured on the basis of knowledge, attitudes and intentions on BC screening. Secondary outcomes are participation rate, satisfaction on information and decisional conflict., Discussion: The web DA will be open-source and implemented on BC screenings and its efficacy for increasing informed choice will be tested. This model could be applied to other healthcare settings, cancer screenings, and public health programs., Trial Registration: The protocol for this trial was registered with the Clinicaltrials.gov registry on March 16, 2017: NCT03097653 .

Introduction: In Italy, due to increasing healthcare budget and staff shortages, the recently created regional mammography screening programmes were established under worse radiology practice quality criteria than the previously created programmes., Methods: Using available data from a national questionnaire survey conducted at the end of 2013 and involving 222 responder radiologists, we compared the main professional quality standards of radiologists working in the screening programmes established during the period 2000-2012 with those working in the screening programmes created from 1990 to 1999., Results: The former reported more years of clinical experience in breast imaging and a greater clinical mammogram reading volume than the latter. Conversely, they dedicated less working time to breast imaging, were less likely to participate in the diagnostic assessment of screen-detected lesions, to work in large-staffed screening centres, and to have a screening and a total mammogram reading volume (SMRV and TMRV) ≥ 5000 per year., Conclusions: The level of most professional quality criteria of Italian mammography screening radiologists has decreased over time. As SMRV and TMRV are important predictors of diagnostic accuracy, we can expect a lower interpretation performance of radiologists working in the recently created screening programmes.

Women who were previously treated for breast cancer (BC) are an important particular subgroup of women at intermediate BC risk. Their breast follow-up should be planned taking in consideration a 1.0-1.5 % annual rate of loco-regional recurrences and new ipsilateral or contralateral BCs during 15-20 years, and be based on a regional/district invitation system. This activity should be carried out by a Department of Radiology integrating screening and diagnostics in the context of a Breast Unit. We recommend the adoption of protocols dedicated to women previously treated for BC, with a clear definition of responsibilities, methods for invitation, site(s) of visits, methods for clinical and radiological evaluation, follow-up duration, role and function of family doctors and specialists. These women will be invited to get a mammogram in dedicated sessions starting from the year after the end of treatment. The planned follow-up duration will be at least 10 years and will be defined on the basis of patient's age and preferences, taking into consideration organizational matters. Special agreements can be defined in the case of women who have their follow-up planned at other qualified centers. Dedicated screening sessions should include: evaluation of familial/personal history (if previously not done) for identifying high-risk conditions which could indicate a different screening strategy; immediate evaluation of mammograms by one or, when possible, two breast radiologists with possible addition of supplemental mammographic views, digital breast tomosynthesis, clinical breast examination, breast ultrasound; and prompt planning of possible further workup. Results of these screening sessions should be set apart from those of general female population screening and presented in dedicated reports. The following research issues are suggested: further risk stratification and effectiveness of follow-up protocols differentiated also for BC pathologic subtype and molecular classification, and evaluation of different models of survivorship care, also in terms of cost-effectiveness., Competing Interests: The authors declare no funding and no conflict of interest for this article. Ethical standards This article does not contain any studies with human participants or animals performed by any of the authors.

Several studies suggest that population-based breast cancer screening programmes might help reduce social inequalities in breast cancer survival both by increasing early diagnosis and by improving access to effective treatments. To start disentangling the two effects, we evaluated social inequalities in quality of treatment of screen-detected breast cancer in the city of Turin (Italy). Combining data from the Audit System on Quality of Breast Cancer Treatment and the Turin Longitudinal Study, we analysed 2700 cases in the screening target age class 50-69 diagnosed in the period 1995-2008. We selected 10 indicators of the pathway of care, relative to timeliness and appropriateness of diagnosis and treatment, and three indicators of socioeconomic position: education, occupational status and housing characteristics. For each indicator of care, relative risks of failure were estimated by robust Poisson regression models, controlling for calendar period of diagnosis, size of tumour and activity volume of the surgery units. The principal predictor of failure of the good care indicators was the calendar period of diagnosis, with a general improvement with time in the quality of diagnosis and treatment, followed by size of the tumour and volume of activity. Socioeconomic indicators show only a marginal independent effect on timeliness indicators. The observed associations of quality indicators with socioeconomic characteristics are lower than expected, suggesting a possible role of the screening programme in reducing disparities in the access to good-quality treatments thanks to its capability to enter screen-detected women into a protected pathway of care.

Purpose: Screening mammogram reading volume (SMRV) and total (screening and clinical) mammogram reading volume (TMRV) per year are strongly associated with the radiologist's diagnostic performance in breast cancer screening. The current article reports the prevalence and correlates of a SMRV and a TMRV ≥5000 among Italian breast screening radiologists., Materials and Methods: A questionnaire survey was carried out in 2013-2014 by the Italian Group for Mammography Screening (GISMa). The questionnaire included items of information for radiologist's experience-related characteristics and for facility-level factors supposedly associated with SMRV and TMRV. Multivariate analysis was performed using backward stepwise multiple logistic regression models., Results: Data for 235 radiologists from 51 local screening programmes were received. Of the 222 radiologists who were eligible, 133 (59.9 %) reported a SMRV ≥5000 and 163 (73.4 %) a TMRV ≥5000. Multivariate factors positively associated with both characteristics included: the number of years of experience reading mammograms; the percentage of total working time dedicated to breast imaging and breast care; the participation in diagnostic assessment; and the availability of digital tomosynthesis at facility. Full-time dedication to breast imaging and breast care was associated with the highest odds ratio for a SMRV and a TMRV ≥5000, i.e. 11.80 and 46.74, respectively, versus a percentage of time ≤50 %. An early (<2000) year of implementation of the screening programme and the availability of vacuum-assisted biopsy at facility were associated with a SMRV and, respectively, a TMRV ≥5000., Conclusions: Increasing the proportion of radiologists with full-time dedication to breast imaging and breast care qualified as the most effective approach to improve SMRV and TMRV.

Objectives: evaluation of a centralised collection of clinical data (Service) within cancer screening programmes in Piedmont based on a hub&spoke model and its impact on process indicators., Design: assessment of an organisational intervention, through a non-controlled pre-post design., Setting and Participants: organised screening programmes within the Piedmont Region, divided into 9 departments., Main Outcome Measures: clinical data (extracted from medical charts for mammography screening and from excision histology reports for cervical screening) obtained through the Service were quantified and their completeness was assessed. The Service impact on the detection rate (DR) was evaluated, comparing the DR pre- (2005-2008) and post-Service (2009- 2012) within breast screening; the DR was computed through histological diagnosis made during colposcopy (pre-Service method) or through the worst diagnosis between the latter and that reported from excision histology (post-Service method) within cervical screening (data available for department 1, year 2013). Some hints on human resources employed in pre- and post-Service periods were reported., Results: within mammography screening, the Service obtained 53.1% of extra-department medical charts and 45.8% of extra-region ones; the percentage of missing diagnoses changed from 5.5% (pre- Service) to 3.7% (post-Service). The age standardised DR for malignant tumours in the post-Service period is 1.3 times the DR of the pre-Service period per 1,000 screening tests. Within cervical screening, 51.7% of histological reports was recorded. Crude DR for high-grade lesions changed from 3.9 (pre-Service) to 4.7 (post-Service) per 1,000 screened women. The system centralisation did not imply an increase in the dedicated personnel., Conclusion: the Service is an operational core which coordinates the collection of clinical data, impacting on process indicators without an increase in human resources at departmental level.

In this position paper, a self-convened team of experts from the Italian Group for Mammography Screening (Gruppo italiano screening mammografico, GISMa) pointed out the problems that increasingly hamper the feasibility and validity of the estimate of the proportional incidence of interval breast cancer (IBC) in Italy, suggested potential solutions and an agenda for research, and proposed that the question of the sensitivity of mammography be viewed in a larger perspective, with a greater attention to radiological review activities and breast radiology quality assurance programmes. The main problems are as follows: the coverage of cancer registration is incomplete; the robustness of using the pre-screening incidence rates as underlying rates decreases with time since the start of screening; the intermediate mammograms performed for early detection purposes may cause an overrepresentation of IBCs; the classification of many borderline screening histories is prone to subjectivity; and, finally, the composition of cohorts of women with negative screening results is uncertain, because several mammography reports are neither clearly negative nor clearly positive, and because of the limitations and instability of the electronic mammography records. Several possibilities can be considered to cope with these issues: standard methods for using the hospital discharge records in the identification of IBCs should be established; for the calculation of regional estimates of the underlying incidence, a suitable mathematical model should be identified; the definition of IBC according to the 2008 GISMa guidelines needs to be updated, especially with respect to in situ cancers and to invasive cancers with borderline screening histories; a closer adherence to standard screening protocols, with a simplified patient management, would make it easier to objectively identify IBCs; alternative methods for estimating the sensitivity of mammography should be taken into consideration; and, finally, analysis could be restricted to the absolute incidence rate of IBC, which would make comparison of the risk between neighbouring populations possible. Epidemiologists must extend their attention to the prevention of the risk of IBC and the implementation of breast radiology quality assurance practices. Epidemiologists and radiologists can share common objectives: it is necessary to promote the idea that the availability of a registry-based series of IBCs is not a prerequisite for their radiological review; radiological review of breast cancers greater than 20mm in size detected at second and subsequent screens, that are potential substitutes for IBCs, needs radiological and epidemiological validation studies; the advent of digital mammography brings about the possibility to create libraries of mammograms accessible online, which enables the conduct of large studies of the diagnostic variability of radiologists; and, finally, epidemiologists and radiologists have the responsibility to monitor the effects that a loss of cumulative professional experience in screening centres, due to the imminent retirement of a substantial proportion of healthcare workforce, could cause on their performance.

In this report, we present the results of cancer screening programmes in Italy for the years 2011-2012. This report is produced by the National centre for screening monitoring (ONS), together with the Italian professional multidisciplinary screening groups: GISMa (Italian group for mammographic screening), GISCor (Italian group for colorectal screening), and GISCi (Italian group for cervical screening). Since 2004, ONS has been monitoring and supporting Italian screening programmes, in accordance with a decree issued by the Ministry of Health. Multidisciplinary groups work with ONS and provide the know-how required to promote the quality of public health programmes. The following is a brief outline of the Italian screening programme setting: screening programmes (cervical, mammographic, colorectal) have been a Basic Healthcare Parameter (livello essenziale di assistenza, LEA) since 2001; guidelines are provided by the Ministry of Health's Department of Prevention in agreement with regional governments; regional governments are responsible for the organization, management, and quality assurance of screening programmes; since 2004, ONS has been responsible for monitoring and promoting screening programmes nationwide; the results of the screening programmes of each region are evaluated annually by the Ministry of Health in terms of coverage and impact.

Together with the National centre for screening monitoring (ONS), GISMa supports annual collection of data on national breast screening activities. Aggregated data on implementation and performance are gathered through a standardized form to calculate process and impact indicators. Analyzed data belong to 153 local programmes in the period 2006-2011 (2006-2012 for participation rate only). During the whole period, Italian crude participation rate exceeded GISMa's acceptable standard (50%), even though a higher participation in northern and central Italy compared to southern Italy and Islands was observed. Time trend analysis of diagnostic indicators confirmed in 2011 an adequate quality of breast screening performance, especially at subsequent screening. Recall rate at initial screening did not reach the acceptable standard (<7%) and rose slightly over the period. On the contrary, a good performance was achieved at subsequent screening. The same trend was followed by the overall detection rate and positive predictive value. They both showed a progressive reduction (from 6.2‰ in 2006 to 4.5‰ in 2011 for DR and from 8.0% in 2006 to 5.2% in 2011 for PPV, respectively) at initial screening and a good, stable trend at subsequent screening. Activity volume analysis shows that in programmes with greater activity (test/year ≥10,000) RR at both initial and subsequent screening has a better performance. This is also true for DR and PPV where programmes with high volumes of activity do better, especially when compared with those that interpret fewer than 5,000 mammograms per year. In spite of a few limits, these results are reassuring, and they reward the efforts made by screening professionals. It is therefore important to continue to monitor screening indicators and suggest, test, and evaluate new strategies for continuous improvement.

Debate on efficacy, benefits, and risks of breast cancer screening continues to rage, and scientific controversy surrounding overdiagnosis, false positives/false negatives, raises questions about communication to women attending screening programmes. The study compares information provided by invitation letters and leaflets of Italian breast screening programmes in 2001 (N=47) and 2014 (N=80). At both times, nearly all programmes provided adequate practical information and details about screening objectives and test procedures. Information regarding epidemiology/figures was scarce or absent in 2001, while in 2014 a number of programmes began to inform women about screening risks (false negative and positive results and overdiagnosis, 65%, 16%, and 21% respectively) although actual figures were rarely supplied. Despite this small improvement, Italian programmes are still far from giving balanced information. Further efforts should be addressed to providing accurate and transparent information, enabling women to make an informed choice.

This report is an update of a number of papers that have been published by the ONS (Osservatorio nazionale screening, National centre for screening monitoring) since 2002. Data for the survey come from several programmes that may have changed over time, and may have different settings of organization and management. During 2011-2012, a slight increase in actual extension was recorded compared to the previous years. Currently, all Italian regions have implemented screening programmes. In 2011-2012, almost 5,300,000 women aged 50-69 years were invited to have a screening mammogram, and almost 3,000,000 were screened.While potential extension was 94.4%, actual extension was 73.3%. An imbalance in extension is still present when comparing northern and central Italy, that have an actual screening extension of 94% and 86% respectively, to southern Italy, that has less than 40%. During the last few years, participation rates have been substantially stable, at around 56%for crude rate, and 60% for adjusted rate, respectively. Women actually screened during 2011-2012 were 38.9%of the national target population. Referral rates of 9.2%at first screening and 4.7%at repeat screening were recorded, showing an increasing trend in recent years. Detection rate was 4.8x1,000 at first screening and 4.4x1,000 at repeat screening, while benign to malignant surgical biopsy ratio for first and repeat screening was 0.2 and 0.1, respectively. Detection rate of small (≤10 mm) invasive cancers was 1.3x1,000 at first screening and 1.4x1,000 at repeat screening; the proportion of in situ carcinomas was 13.3%and 12.0%for first and repeat screening, respectively. Indicators by 5-year age group confirm greater diagnostic problems at younger ages (50-54 years), with higher referral rates and a substantially lower detection rate as compared to older age groups.

Background: Due to its low cardiac toxicity, non-pegylated liposomal doxorubicin (NPLD) may represent an attractive therapeutic option as salvage therapy for patients with metastatic breast cancer who have already received anthracycline-based chemotherapy., Patients and Methods: We retrospectively reviewed 47 consecutive patients with metastatic breast cancer treated with NPLD at our Institution between 2008 and 2012. Patients received weekly NPLD at a dose of 20 mg/m(2) i.v. until disease progression or unacceptable toxicity., Results: Nine patients (19.1%) achieved a partial response and 11 (23.4%) had stable disease, with a disease control rate of 42.6%; 27 patients (57.4%) had progressive disease. The median progression-free survival and overall survival were 2.7 and 11.5 months, respectively. Grade 3 and 4 adverse events did not occur. No cardiac events were observed., Conclusion: Weekly NPLD represents a safe and effective therapy and may be considered a new therapeutic option for heavily pre-treated patients with metastatic breast cancer.

Background: The level of HER2/neu amplification may vary widely in breast cancers with HER2/neu alteration. The clinical significance of this phenomenon is still unclear. This study was aimed to explore the level of HER2/neu amplification in primary tumours and metastases in HER2-positive metastatic breast cancer (MBC) and its potential impact on survival after a trastuzumab-containing therapy., Methods: We retrospectively identified MBC patients treated with a trastuzumab-containing therapy and performed dual-colour FISH on tumour samples from either primary tumour and/or metastasis in a central laboratory., Results: We retrieved 110 tumour samples from 91 patients and included 79 tumour samples (primary = 56; metastasis = 23) from 63 patients in the final analysis. We found higher level of HER2/neu amplification in the metastases than in the primary tumours (median HER2/CEP17 ratio: 10.5 vs. 7.0, respectively). In 69% of patients (n = 16) with two tumour samples, the level of HER2/neu amplification was higher in the metastasis than in the paired primary tumour (median HER2/CEP17 ratio: 10.9 vs. 8.3, respectively, p = 0.004). The incremental gain in level of HER2/neu amplification was associated with significantly shorter OS after trastuzumab-containing therapy (p = 0.023, HR 1.014, CI95%: 1.002-1.025)., Conclusions: The level of HER2/neu amplification tends to increase from the primary tumour to the paired metastases in a significant proportion of patients with HER2-positive MBC. This phenomenon, although still not completely understood, could lead to a shorter OS after trastuzumab therapy., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Since its establishment in 1990, one of the main tasks of the Italian group for breast cancer screening (GISMa) is the systematic data collection on the activity of the organised breast cancer screening programmes implemented in Italy. Data are collected in an aggregated way and gathered through a standardised form to calculate process and impact parameters. Data analysis from 2000-2010 shows that crude attendance rate reached the acceptable 50% standard, presenting a higher level of participation in Northern and Central Italy compared to Southern Italy/Islands, where attendance rates are still inadequate and do not reach the acceptable standard. In areas where a more complete regional extension (referring frequently to a more centralised management) exists, the participation rate was higher compared to those with partial regional extension and no centralised management. The differences range from 5% in 2005 to 22% in 2010. The time trends of the other analysed parameters showed, in 2010, a good overall quality of the performance. For example, benign/malignant surgical biopsy ratio (B/M ratio) reached 0.19 at first screening and 0.11 at subsequent screening; detection rate for in situ and small cancers (≤10 mm) showed a good trend, reaching 0.9‰ and 1.2‰, respectively, at first screening, and 0.6‰, and 1.5‰ for subsequent screening, respectively. On the contrary, excess referral rate at first screening persisted (9.2%) in the year 2010, while RR is improved at subsequent screening (from 4.2% in 2009 to 3.9% in 2010). The overall detection rate is improved both at first and subsequent screening (5.2‰ in 2010 vs. 5.7‰ in 2009 and 4.7‰ in 2010 vs. 5.7‰ in 2009, respectively). Although further analyses are needed to better interpret these trends, results continue to be consistent with those achieved by other European programmes, and they are reassuring for all Italian breast cancer screening professionals.

This report is an update of similar previous papers that have been published by the ONS (Osservatorio nazionale screening, National Centre for Screening Monitoring) since 2002. Data for the survey come from several different programmes that may have changed over time, and may have different settings of organisation and management. During 2010, the first slight decrease in theoretical extension was recorded. Currently, all Italian regions have implemented screening programmes. In 2010, almost 2,496,000 women aged 50-69 years were invited to have a screening mammogram, and more than 1,382,000 were screened. Theoretical extension was 91.7%, while actual extension was 69.1%. An imbalance in extension is still present when comparing northern and central Italy to southern Italy, which only has a 75% coverage by organised screening. The Italian mean value (69%) of two-year extension (period 2009-2010) suggests that, at full capacity, Italian programmes are able to invite only three quarters of the target population. The percentage of women screened during 2010 was 36.7% of the national target population. During the last few years, participation rates were substantially stable, around 55-57% for crude rate, and 59-61% for adjusted rate, respectively. A decreasing trend towards the South of Italy is evident for this parameter, too. Many programmes work with low volumes of activity (below 10,000 or even 5,000 examinations per year), and only one region surpassed the desirable level of at least 20,000 examinations for each programme. Referral rates of 8.8% at first screening and 4.6% at repeat screening were recorded. Direct standardised detection rate was 6.2x1,000 at first screening and 4.3x1,000 at repeat screening, while benign to malignant ratio for first and repeat screening was 0.26 and 0.12, respectively. Detection rate of invasive cancers ≤10 mm was 1.36x1,000 at first screening and 1.49x1,000 at repeat screening; the proportion of in situ carcinomas was 13.9% and 13.4% for first and repeat screening, respectively. Indicators by 5-year age group confirm greater diagnostic problems at younger ages (50-54 years), with higher referral rates, higher frequency of surgical procedures with benign outcome (B/M ratio), and a substantially lower detection rate as compared to older age groups.

Background: Several factors can influence access to population breast cancer screening. The aim of the study was to evaluate the impact of different information approaches, women's socio-demographic characteristics and organizational factors on mammography screening uptake., Methods: We selected 5744 women aged 40-45 years who were randomly assigned to be given letters with: (i) a pre-fixed appointment plus standard leaflet (Group 1); (ii) a pre-fixed appointment plus a more comprehensive booklet (Group 2); (iii) point (ii) plus the offer of a counselling session (Group 3); and (iv) an invitation to contact the centre to get information and arrange participation (Group 4)., Results: Ninety-five women were excluded before the invitation and 5649 were randomized. After excluding undelivered letters (n = 41) and women reporting an exclusion criterion following our invitation (n = 248), the final eligible population was 5360 women. Participation rates following the first contact were 36.5, 39.9, 35.8 and 16.5% for Groups 1-4, respectively. The rates increased to 40.9, 43.6, 40.1 and 35.1% after the reminder letters. Women receiving more complete information had a higher uptake (Group 2), although not statistically significant. Differences among the four groups were maintained by controlling the effect of socio-demographic and attendance determinants. Regardless of intervention, participation was higher among married, higher educated, white-collared women, those born in northern Italy, living closer to the screening unit and with a female-collaborative doctor., Conclusion: Invitation letters with a fixed appointment correlate with a higher attendance rate. Providing women with more information on procedures, risks and benefits of mammography screening does not modify their participation.

Objectives: To summarize participation and coverage rates in population mammographic screening programmes for breast cancer in Europe., Methods: We used the European Network for Information on Cancer (EUNICE), a web-based data warehouse (EUNICE Breast Cancer Screening Monitoring, EBCSM) for breast cancer screening, to obtain information on programme characteristics, coverage and participation from its initial application in 10 national and 16 regional programmes in 18 European countries., Results: The total population targeted by the screening programme services covered in the report comprised 26.9 million women predominantly aged 50-69. Most of the collected data relates to 2005, 2006 and/or 2007. The average participation rate across all programmes was 53.4% (range 19.4-88.9% of personally invited); or 66.4% excluding Poland, a large programme that initiated personal invitations in 2007. Thirteen of the 26 programmes achieved the European Union benchmark of acceptable participation (>70%), nine achieved the desirable level (>75%). Despite considerable invitation coverage across all programmes (79.3%, range 50.9-115.2%) only 48.2% (range 28.4-92.1%) of the target population were actually screened. The overall invitation and examination coverage excluding Poland was 70.9% and 50.3%, respectively., Conclusions: The results demonstrate the feasibility of European-wide screening monitoring using the EBCSM data warehouse, although further efforts to refine the system and to harmonize standards and data collection practices will be required, to fully integrate all European countries. The more than three-fold difference in the examination coverage should be taken into account in the evaluation of service screening programmes.

Objective: Despite the difficulties, there is a moral responsibility to provide the public with the best estimates of benefits and harms of breast cancer screening., Methods: In this paper we review the issues in communication of benefits and harms of medical interventions and discuss these in terms of the principles of the balance sheet proposed in this supplement., Results: The balance sheet can be seen as a tool to convey estimates based on the best available evidence and addressed to a readership wider than just potential screening participants. It reflects a re-assessment of screening efficacy, showing again that screening is effective and brings more benefits than harms. It can be viewed as an opportunity to re-affirm some basic principles of good evidence-based communication. Further research is needed to improve communication strategy, to assess the impact of this communication on women's awareness and to evaluate its utility in the informed decision-making process., Conclusion: The balance sheet could be a starting point for a broader vision of informed decision-making in screening, which should also recognize the role played by 'non-numerical' factors on women's choice of participating in breast cancer screening.

Objective: To estimate the cumulative risk of a false-positive screening result in European mammographic screening programmes, and examine the rates and procedures of further assessment., Methods: A literature review was conducted to identify studies of the cumulative risk of a false-positive result in European screening programmes (390,000 women). We then examined aggregate data, cross-sectional information about further assessment procedures among women with positive results in 20 mammographic screening programmes from 17 countries (1.7 million initial screens, 5.9 million subsequent screens), collected by the European Network for Information on Cancer project (EUNICE)., Results: The estimated cumulative risk of a false-positive screening result in women aged 50-69 undergoing 10 biennial screening tests varied from 8% to 21% in the three studies examined (pooled estimate 19.7%). The cumulative risk of an invasive procedure with benign outcome ranged from 1.8% to 6.3% (pooled estimate 2.9%). The risk of undergoing surgical intervention with benign outcome was 0.9% (one study only). From the EUNICE project, the proportions of all screening examinations in the programmes resulting in needle biopsy were 2.2% and 1.1% for initial and subsequent screens, respectively, though the rates differed between countries; the corresponding rates of surgical interventions among women without breast cancer were 0.19% and 0.07%., Conclusion: The specific investigative procedures following a recall should be considered when examining the cumulative risk of a false-positive screening result. Most women with a positive screening test undergo a non-invasive assessment procedure. Only a small proportion of recalled women undergo needle biopsy, and even fewer undergo surgical intervention.

Since its establishment in 1990, one of the main tasks of the Italian group for mammography screening (GISMa) is the systematic data collection on the activity of the organised mammography screening programmes implemented in Italy. Data are collected in an aggregated way and gathered through a standardised form to calculate process and impact parameters. Data analysis from 1999-2009 shows that crude attendance rate reached the acceptable 50% standard, presenting a higher level of participation in northern and central Italy compared to southern Italy/Islands, where attendance rates are still inadequate and do not reach the acceptable standard. In areas where centralised management is more established or complete, the participation rate was higher compared to areas without such characteristics, with differences from 5% in 2005 (reaching 22% in 2008) to 10% in 2009. The time trends of the other parameters included in the analysis showed, in 2009, a good average performance. For example, benign/malignant surgical biopsy ratio (B/M ratio) reached 0.21 at first screening and 0.08 at subsequent screening; detection rate for in situ and small cancers (≤10 mm) showed a good trend, reaching 0.9‰, and 1.5‰, respectively, for first screening, and 0.9‰, and 1.4‰ for subsequent screening. On the contrary, excess referral rate at first screening persisted, and the overall detection rate presented a negative trend in the last period (8.9% and 5.7‰, respectively). Although further analyses are needed to better interpret these trends, results continue to be consistent with those achieved by other European programmes, and are reassuring for all Italian mammography screening professionals.