Breast Cancer: A Multi-Disciplinary Approach from Imaging to Therapy.

Breast cancer (BC) is the most prevalent form of cancer among women worldwide, accounting for over 2 million diagnoses annually [...].

Practical Challenges of DBT-Guided VABB: Harms and Benefits, from Literature to Clinical Experience.

Vacuum-assisted breast biopsy (VABB) guided by digital breast tomosynthesis (DBT) represents one of the best instruments to obtain a histological diagnosis of suspicious lesions with no ultrasound correlation or those which are visible only on DBT. After a review of the literature, we retrospectively analyzed the DBT-guided VABBs performed from 2019 to 2022 at our department. Descriptive statistics, Pearson's correlation and χ2 test were used to compare distributions of age, breast density (BD) and early performance measures including histopathology. We used kappa statistics to evaluate the agreement between histological assessment and diagnosis. Finally, we compared our experience to the literature to provide indications for clinical practice. We included 85 women aged 41-84 years old. We identified 37 breast cancers (BC), 26 stage 0 and 11 stage IA. 67.5% of BC was diagnosed in women with high BD. The agreement between VABB and surgery was 0.92 (k value, 95% CI: 0.76-1.08). We found a statistically significant inverse correlation between age and BD. The post-procedural clip was correctly positioned in 88.2%. The post-procedural hematoma rate was 14.1%. No infection or hemorrhage were recorded. When executed correctly, DBT-guided VABB represents a safe and minimally invasive technique with high histopathological concordance, for detecting nonpalpable lesions without ultrasound correlation.

Breast Density Evaluation According to BI-RADS 5th Edition on Digital Breast Tomosynthesis: AI Automated Assessment Versus Human Visual Assessment.

BACKGROUND: The assessment of breast density is one of the main goals of radiologists because the masking effect of dense fibroglandular tissue may affect the mammographic identification of lesions. The BI-RADS 5th Edition has revised the mammographic breast density categories, focusing on a qualitative evaluation rather than a quantitative one. Our purpose is to compare the concordance of the automatic classification of breast density with the visual assessment according to the latest available classification. METHODS: A sample of 1075 digital breast tomosynthesis images from women aged between 40 and 86 years (58 ± 7.1) was retrospectively analyzed by three independent readers according to the BI-RADS 5th Edition. Automated breast density assessment was performed on digital breast tomosynthesis images with the Quantra software version 2.2.3. Interobserver agreement was assessed with kappa statistics. The distributions of breast density categories were compared and correlated with age. RESULTS: The agreement on breast density categories was substantial to almost perfect between radiologists (κ = 0.63-0.83), moderate to substantial between radiologists and the Quantra software (κ = 0.44-0.78), and the consensus of radiologists and the Quantra software (κ = 0.60-0.77). Comparing the assessment for dense and non-dense breasts, the agreement was almost perfect in the screening age range without a statistically significant difference between concordant and discordant cases when compared by age. CONCLUSIONS: The categorization proposed by the Quantra software has shown a good agreement with the radiological evaluations, even though it did not completely reflect the visual assessment. Thus, clinical decisions regarding supplemental screening should be based on the radiologist's perceived masking effect rather than the data produced exclusively by the Quantra software.

Mammography in Breast Disease Screening and Diagnosis.

Female breasts can suffer from a wide spectrum of pathologies, ranging from inflammatory diseases to benign and malignant tumors [...].

Consequences of the impact of COVID-19 pandemic on breast cancer at a single Italian institution.

Aim: To evaluate the local impact of the coronavirus disease 2019 (COVID-19) pandemic on breast cancer (BC) care, with particular attention to the economical and psychological consequences of the possible delay of new diagnoses and treatments. Methods: Three years' activity (from 2019 to 2021) has been compared. The number of BCs diagnosed from the total amount of mammographic and ultrasound (US) examinations performed in women aged more than 40 years old has been considered. A Pearson's chi-squared test was performed to verify differences between results. Statistical significance was set at P ≤ 0.01. Results: A statistically significant difference was found in the number of BC diagnosed between screening and ambulatory care patients in both the 2019-2020 (χ2 = 24.93, P < 0.01) and 2019-2021 (χ2 = 29.93, P < 0.01) comparisons. No statistically significant difference was found in the data recorded between 2020 and 2021 (χ2 = 2.35, P > 0.01). By evaluating the specific age groups for each year, a statistically significant difference (P < 0.01) was found in the number of BC diagnosed in screening patients aged 50-69 years old in both 2019-2020 and 2019-2021 comparisons. The percentages of early BC diagnosed in 2019, 2020, and 2021 were 80.9%, 91.7%, and 89.8%, respectively. The adherence rates to screening in 2019, 2020, and 2021 were 67.5%, 45.2%, and 56.9%, respectively. Conclusions: Results showed a reduction of new diagnoses in the screening range during the pandemic in comparison with the previous period. The high percentage of early BC would seem to have prevented worsening outcomes. Nevertheless, women who have not undergone screening could present a more advanced stage disease in the following years. Consequently, the evaluation of possible solutions to guarantee an essential level of care with the purpose to avoid worsening patients' outcomes and the increase in healthcare costs is mandatory.

Special Issue "New Advances in Breast Imaging".

Breast cancer (BC) is the most common cancer in women of all ages, with more than 2 million diagnoses every year and a high economic and psychological impact on both the health care system and the population [...].

Male Breast Cancer Review. A Rare Case of Pure DCIS: Imaging Protocol, Radiomics and Management.

Ductal carcinoma in situ (DCIS) of male breast is a rare lesion, often associated with invasive carcinoma. When the in situ component is present in pure form, histological grade is usually low or intermediate. Imaging is difficult as gynaecomastia is often present and can mask underlying findings. We report a rare case of pure high-grade DCIS in a young male patient, with associated intraductal papilloma and atypical ductal hyperplasia. Digital breast tomosynthesis (DBT) showed an area of architectural distortion at the union of outer quadrants of the left breast without gynaecomastia. Triple assessment suggested performing a nipple-sparing mastectomy, which revealed the presence of a focal area of high-grade DCIS of 2 mm. DCIS, even of high grade, is difficult to detect with mammography and even more rare, especially when associated with other proliferative lesions. DBT with 2D synthetic reconstruction is useful as the imaging step of a triple assessment and it should be performed in both symptomatic and asymptomatic high-risk men to differentiate between malignant and benign lesions. We propose a diagnostic model to early detect breast cancer in men, optimizing resources according to efficiency, effectiveness and economy, and look forward to radiomics as a powerful tool to help radiologists.

The management of a breast unit during the COVID-19 emergency: a local experience.

Introduction: Since breast imaging requires very close contact with patients, a protocol is needed to perform safe daily screening activities during the COVID-19 pandemic. Materials and methods: Patients were triaged and separated into three different clinical scenarios by performing a telephone questionnaire before each diagnostic exam or a nasopharyngeal swab before every recovery. Specific procedures for each scenario are described. Results: From July to October 2020, 994 exams were performed. A total of 16 cancers and 7 suspected COVID-19 patients were identified. No medical staff were infected. Conclusion: This protocol is an example of the practical use of guidelines applied to a breast unit to assist specialists in preventing COVID-19 infection and optimizing resources for breast cancer diagnosis.

Lay abstract On March 11th, 2020, the WHO officially declared the COVID-19 infection pandemic. Since breast cancer represents the most frequent cancer in women of all ages, and breast imaging examinations require very close contact with patients, a protocol was designed to optimize the management of patients and healthcare workers, performing strict COVID-19 screening and avoiding any impairment of survival of patients with breast cancer. Patients were separated into three different clinical scenarios (non-COVID-19 patients, suspected COVID-19 patients and confirmed COVID-19 patients) by performing a telephone questionnaire before each diagnostic exam or a nasopharyngeal swab before every recovery. Specific procedures for each scenario are described. Confirmed or suspected patients are rescheduled if not urgent. From July to October 2020, 994 exams were performed. A total of 16 cancers and 7 suspected COVID-19 patients were identified. No medical staff were infected. This study demonstrates efficacy in terms of continuity in the provision of an essential level of care in a breast cancer screening and ambulatory setting, providing an example of the practical use of guidelines applied to a breast unit, to assist specialists in preventing COVID-19 infection and optimizing resources for breast cancer diagnosis.

Breast Cancer Screening during COVID-19 Emergency: Patients and Department Management in a Local Experience.

BACKGROUND: During the COVID-19 public health emergency, our breast cancer screening activities have been interrupted. In June 2020, they resumed, calling for mandatory safe procedures to properly manage patients and staff. METHODS: A protocol supporting medical activities in breast cancer screening was created, based on six relevant articles published in the literature and in the following National and International guidelines for COVID-19 prevention. The patient population, consisting of both screening and breast ambulatory patients, was classified into one of four categories: 1. Non-COVID-19 patient; 2. Confirmed COVID-19 in an asymptomatic screening patient; 3. suspected COVID-19 in symptomatic or confirmed breast cancer; 4. Confirmed COVID-19 in symptomatic or confirmed breast cancer. The day before the radiological exam, patients are screened for COVID-19 infection through a telephone questionnaire. At a subsequent in person appointment, the body temperature is checked and depending on the clinical scenario at stake, the scenario-specific procedures for medical and paramedical staff are adopted. RESULTS: In total, 203 mammograms, 76 breast ultrasound exams, 4 core needle biopsies, and 6 vacuum-assisted breast biopsies were performed in one month. Neither medical nor paramedical staff were infected on any of these occasions. CONCLUSION: Our department organization model can represent a case of implementation of National and International guidelines applied in a breast cancer screening program, assisting hospital personnel into COVID-19 infection prevention.

Direct healthcare costs of chronic kidney disease management in Italy: What cost-savings can be achieved with higher biosimilar uptake and more appropriate use of erythropoiesis-stimulating agents?

PURPOSE: Erythropoiesis-stimulating agents (ESAs), are used for treating chronic kidney disease (CKD)-related anemia, contributing to CKD costs. The study was aimed at investigating direct healthcare costs of CKD patients treated with ESAs and the potential savings achievable by increasing the use of biosimilars and preventing inappropriate ESA use. METHODS: A multi-center, cohort study was conducted using claims databases of five large Italian geographic areas. Yearly mean direct healthcare costs per patient were estimated, stratifying by CKD stage. The total yearly cost and potential savings related to ESA use were estimated: (a) considering 25/50/75% of originator ESA substitution with biosimilars; (b) eliminating inappropriate ESA dispensing. RESULTS: During the study period, the ESA-related yearly mean cost represented 17% of total yearly costs in stage I-III, decreasing to 13% in stage IV-V and 6% in dialysis. Among originator users, assuming a 25% of biosimilar uptake, the annual cost-savings of ESA treatment would represent 10.5% of total ESA costs in CKD stage I-V and 7.7% in dialysis. Among incident ESA users for which hemoglobin levels were available, 9% started inappropriately ESA treatment, increasing to 62.0% during the first year of maintenance therapy. Hypothesizing prevention of the first inappropriate ESA dispensing, the total yearly cost-savings would amount to €35 772, increasing to €167 641 eliminating the inappropriate dispensing during maintenance therapy. CONCLUSIONS: Higher use of lowest cost ESA, prevention of inappropriate ESA use as well as other strategies aimed at slowing down the progressive renal impairment are essential for minimizing clinical and economic burden of CKD.

Correction to: In search of potential predictors of erythropoiesis-stimulating agents (ESAs) hyporesponsiveness: a population-based study.

An amendment to this paper has been published and can be accessed via the original article.

In Search of Predictors of Switching Between Erythropoiesis-Stimulating Agents in Clinical Practice: A Multi-Regional Cohort Study.

BACKGROUND AND OBJECTIVES: Switching between different erythropoiesis-stimulating agents (ESAs) during the first year of therapy is frequent (15-20%), much more so toward reference products than biosimilars. The objectives of this study were to investigate the frequency and identify the potential predictors of switching between biosimilar and originator ESAs during the first year of treatment in patients with chronic kidney disease (CKD), or chemotherapy-related anemia from six large Italian geographic areas in the years 2009-2015. METHODS: A retrospective cohort study was conducted using six Italian regional claims databases (≥ 13 million inhabitants) during 2009-2015. Among incident epoetin users, the frequency of single, multiple, and backward switch during the first year of treatment was evaluated. Using frailty Cox models, potential predictors of first switch were identified. All analyses were stratified by the main indications for use. RESULTS: Among 102,240 incident epoetin users, 15,853 (15.5%) switched to another epoetin during the first year of therapy; only 18% of these switched to biosimilars. Single switch was more common (62.2% of the switchers) than multiple (23.5%) or backward switch (14.3%). In cancer, the cumulative number of transfusions and iron preparations dispensed, as well as hyperparathyroidism, were predictors of switching. In CKD, the cumulative number of transfusions, number of vitamin A/D preparations dispensed, and CKD severity increased the probability of switching. CONCLUSIONS: Switching between ESAs was frequent in both CKD and cancer patients. The number of cumulative transfusions and severity of disease seemed to affect the switch.

Analgesic drug use in elderly persons: A population-based study in Southern Italy.

INTRODUCTION: Analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs), weak and strong opioids are commonly used among elderly persons. The aim of this study was to describe the demographic and clinical characteristics of elderly analgesic users and to measure the frequency of analgesic use, including the frequency of potentially inappropriate analgesic use. METHODS: The Arianna database was used to carry out this study. This database contains prescription data with associated indication of use for 1,076,486 inhabitants registered with their general practitioners (GPs) in the Caserta Local Health Unit (Caserta district, Campania region in Italy). A cohort of persons aged ≥65 years old with >1 year of database history having at least one analgesic drug (NSAIDs, strong or weak opioids) between 2010 and 2014 were identified. The date of the first analgesic prescription in the study period was considered the index date (ID). RESULTS: From a source population of 1,076,486 persons, 116,486 elderly persons were identified. Of these, 94,820 elderly persons received at least one analgesic drug: 36.6% were incident NSAID users (N = 36,629), while 13.2% were incident weak opioid users (N = 12,485) and 8.1% were incident strong opioid users (N = 7,658). In terms of inappropriate analgesic use, 9.2% (N = 10,763) of all elderly users were prescribed ketorolac/indomethacin inappropriately, since these drugs should not be prescribed to elderly persons. Furthermore, at least half all elderly persons with chronic kidney disease or congestive heart failure were prescribed NSAIDs, while these drugs should be avoided. CONCLUSION: Analgesics are commonly used inappropriately among elderly persons, suggesting that prescribing practice in the catchment area may yet be improved.

Antipsychotic utilization patterns among patients with schizophrenic disorder: a cross-national analysis in four countries.

PURPOSE: The aim of the present study was to describe antipsychotic utilization patterns among patients with schizophrenic disorder in Italy, Spain, the UK, and the USA. METHODS: A retrospective cohort study was conducted. Patients aged 15 and over with schizophrenic disorder were identified in the Caserta claims database (Italy), the Valencia electronic medical record (EMR) database (Spain), in The Health Improvement Network EMR database (UK), and in databases of publicly and privately insured populations in the United States (US). RESULTS: The frequency of first-generation or second-generation antipsychotic use and of long-acting or other formulations was described. Persistence to antipsychotics was estimated. Overall, 1,403,240 patients with schizophrenic disorder having a total of 765,573 new antipsychotic treatment episodes were identified. The median follow-up time ranged from 0.8 (IQR 0.2-1.9) years in the US commercially-insured population to 1.2 (IQR 0.1-1.7) years in the Spanish population. Second-generation antipsychotics were more frequently used than first-generation antipsychotics in all countries (on average, from 64.4% in the UK to 87% in US): the use of this class increased over time in Italy, Spain, and US (Medicaid). The use of long-acting formulations was heterogeneous across countries, but generally much lower than other formulations. Persistence to antipsychotic treatment at 1 year was low in all countries, ranging from 40 in Spain to 30% in Italy. CONCLUSIONS: Antipsychotic utilization was heterogeneous among persons with schizophrenic disorder. Nevertheless, low persistence was an issue in all the countries, as less than half of the patients continued their treatment beyond 1 year.

Pattern of Use of Biosimilar and Originator Somatropin in Italy: A Population-Based Multiple Databases Study During the Years 2009-2014.

PURPOSE: Somatropin [recombinant growth hormone (rGH)] is approved in children and adults for several conditions involving growth disturbances and the corresponding biosimilar is available in Italy since 2006. No population-based data are available on the pattern of rGH use in Italian clinical practice. This study aimed at exploring the pattern of biosimilar and originator rGH use in six Italian centers, where different policy interventions promoted biosimilar use. METHODS: This population-based, drug-utilization study was conducted in the years 2009-2014, using administrative databases of Umbria, Tuscany, and Lazio Regions and Local Health Units of Caserta, Treviso, and Palermo. Naïve rGH users were characterized, and prevalence of use and discontinuation were assessed over time. RESULTS: Among 6,785 patients treated with rGH during the study years, 4,493 (66.2%) were naïve users (males/females = 1.3), mostly affected by GH deficiency. The prevalence of rGH use increased from 2009 to 2010, remaining stable thereafter, but it was heterogeneous across centers (twofold higher prevalence of use in center n.2 than centers n.4 and 1 in 2014). Biosimilar rGH uptake increased over time but was low (7.8% in 2014) and heterogeneous as well. Discontinuation of rGH therapy occurred in 54.0% of naïve users, more frequently in females than males (58.1 vs. 50.9%). During the first year of treatment, discontinuation was frequent (39.9%), but no statistically significant differences were observed in treatment persistence for biosimilar vs. originator rGH (p > 0.05). CONCLUSION: Geographical heterogeneity in the prevalence of rGH use was observed. Similarly, the biosimilar rGH uptake was low and variable across centers. Post-marketing monitoring is required to continuously monitor the benefit-risk profile of rGH, thus guaranteeing greater savings than only promoting lowest cost rGH.

How Much Are Biosimilars Used in Clinical Practice? A Retrospective Italian Population-Based Study of Erythropoiesis-Stimulating Agents in the Years 2009-2013.

PURPOSE: To explore the prescription patterns of erythropoiesis-stimulating agents (ESAs) in four large Italian geographic areas, where different health policy interventions to promote biosimilar use in routine care are undertaken. METHODS: A retrospective drug utilization study was conducted during the years 2009-2013. The data sources were the administrative databases of the Tuscany region and of the Caserta, Palermo, and Treviso Local Health Units (LHUs). The characteristics, prevalence, and switching patterns of different ESAs (biosimilars and reference products), stratified by indication for use, were calculated over time and across centers. RESULTS: Overall, 49,491 patients were treated with ESAs during the years 2009-2013 in the four centers. Of these, 41,286 patients (83.4 %) were naive users. The prevalence of ESA use increased from 2.9 to 3.4 per 1000 inhabitants in the years 2009-2011 but decreased thereafter (3.0 per 1000 in 2013). Moreover, the proportion of biosimilar users increased overall from 1.8 % in 2010 to 33.6 % in 2013, with larger increase in Treviso (from 0.0 to 45.0 %) and Tuscany (from 0.7 to 37.6 %) than in Caserta (from 7.5 to 22.9 %) and Palermo (from 0.0 to 27.7 %). Switching between different ESAs during the first year of therapy was frequent (17.0 %), much more toward reference products than toward biosimilars. CONCLUSION: Overall, the prevalence of ESA use decreased slightly, while use of biosimilar ESAs, especially in naive patients, increased significantly but to different extents in these four large Italian geographic areas. Switching between different ESAs during the first year of treatment was very frequent, which may affect pharmacovigilance monitoring. New strategies are necessary to further improve market penetration of low-cost medicines, such as biosimilars, and also to harmonize effective health policy interventions that aim to reduce pharmaceutical expenses and optimize patient benefit across all regions.

Association of individual non-steroidal anti-inflammatory drugs and chronic kidney disease: a population-based case control study.

BACKGROUND: Non-steroidal anti-inflammatory agents (NSAIDs) are known to be associated with renal damage. No clear evidence exists regarding differential risk of chronic kidney disease (CKD), specifically, across various NSAIDs. AIM: The aim of this population-based case-control study was to evaluate the association between use of individual NSAIDs and risk of CKD in a general population of Southern Italy. METHODS: A nested case-control study was carried out using the general practice Arianna database, identifying incident CKD patients as cases and matched controls from 2006 to 2011. The date of first CKD diagnosis was defined as the index date (ID). Conditional logistic regressions were performed to estimate the risk of CKD associated with NSAIDs by class and individual drugs as compared to non-use during different time windows (within one year, six or three months prior to ID), with the latter being defined as current users. Among current users, the effect of cumulative exposure to these drugs was evaluated. RESULTS: Overall, 1,989 CKD cases and 7,906 matched controls were identified. A statistically significant increase in the risk of CKD was found for current users of oxicams (adjusted OR: 1.68; 95% CI: 1.15-2.44) and concerning individual compounds, for ketorolac (adj. OR: 2.54; 95% CI: 1.45-4.44), meloxicam (adj. OR: 1.98; 95% CI: 1.01-3.87) and piroxicam (adj. OR: 1.95; 95% CI: 1.19-3.21). CONCLUSIONS: The risk of CKD varies across individual NSAIDs. Increased risk has been found for ketorolac, which may precipitate subclinical CKD through acute renal damage, and long-term exposure to oxicams, especially meloxicam and piroxicam.

Indications of newer and older anti-epileptic drug use: findings from a southern Italian general practice setting from 2005-2011.

AIMS: The aim of the study was to analyze the prescribing pattern of both newer and older AEDs. METHODS: A population of almost 150 000 individuals registered with 123 general practitioners was included in this study. Patients who received at least one AED prescription over 2005-2011 were identified. The 1 year prevalence and cumulative incidence of AED use, by drug class and individual drug, were calculated over the study period. Potential predictors of starting therapy with newer AEDs were also investigated. RESULTS: The prevalence of use per 1000 inhabitants of older AEDs increased from 10.7 (95% CI10.1, 11.2) in 2005 to 13.0 (95% CI12.4, 13.6) in 2011, while the incidence remained stable. Newer AED incidence decreased from 9.4 (95% CI 8.9, 9.9) in 2005 to 7.0 (95% CI 6.6, 7.5) in 2011, with a peak of 15.5 (95% CI 14.8, 16.1) in 2006. Phenobarbital and valproic acid were the most commonly prescribed AEDs as starting therapy for epilepsy. Gabapentin and pregabalin accounted for most new pain-related prescriptions, while valproic acid and lamotrigine were increasingly used for mood disorders. Female gender (OR 1.36, 95% CI 1.20, 1.53), age ranging between 45-54 years (OR 1.39, 95% CI 1.16, 1.66) and pain as an indication (OR 16.7, 95% CI, 13.1, 21.2) were associated with newer AEDs starting therapy. CONCLUSIONS: Older AEDs were mainly used for epileptic and mood disorders, while newer drugs were preferred for neuropathic pain. Gender, age, indication of use and year of starting therapy influenced the choice of AED type. The decrease of newer AED use during 2007 is probably related to the restricted reimbursement criteria for gabapentin and pregabalin.

How healthy is community-dwelling elderly population? Results from Southern Italy.

PURPOSE: To explore the frequency of polypharmacy, functional and cognitive capacity among the elderly in Southern Italy. METHODS: Population-based retrospective cross-sectional study. Information were retrieved from electronic-geriatric-forms matched by record-linkage to outpatient pharmacy-records. The following domains were collected from geriatric forms: BMI, cognitive capacity (SPMSQ), functional status (Barthel-index), mobility, living condition. Polypharmacy status was categorized as non-polypharmacy (0-4), polypharmacy (5-9) and excessive-polypharmacy (≥10). Prevalence of all variables were stratified by age and polypharmacy group. RESULTS: 88,878 old people received a geriatric assessment in the years 2013-2014. Mean age was 74.8 (±7.3) years, 56.6% females. Proportion of elderly in excessive-polypharmacy increased with age (18.9% in 65-75 age-group; 27.9% in >85). Referring to cognitive capacity, the proportion of lucid patients decreased with age (from 94.3% to 58.1%), while confused patient increased with age (from 4.7% to 30.9%). Proportion of subjects with a decline in cognitive status, functional status and mobility increased in polypharmacy and excessive polypharmacy group. CONCLUSION: Polypharmacy is common in people aged 65 years and older with difficulties in activities of daily living and impaired cognition. Furthermore, its prevalence raises with increasing age. Preventive strategies such us optimization of drug regimen should be performed routinely to reduce risk of adverse-health-events.