Prognostic Value of MRI Assessment of Residual Peritumoral Edema in Breast Cancer Treated With Neoadjuvant Chemotherapy.

BACKGROUND: Peritumoral edema (PE) identified on T2-weighted breast MRI is a factor for poor prognosis in breast cancer. PURPOSE: To assess the prognostic value of residual PE (rPE) in patients with PE positive breast cancer prior to neoadjuvant chemotherapy (NACT) who subsequently underwent curative surgery. STUDY TYPE: Retrospective. POPULATION: In total, 128 patients with nonmetastatic invasive breast cancer who underwent breast MRI before and after NACT. FIELD STRENGTH/SEQUENCE: Axial precontrast 2D fast spin echo T2W fat-suppressed sequence. Axial dynamic 3D gradient echo T1W fat-suppressed sequence. ASSESSMENT: PE was diagnosed when a signal intensity as high as water was detected surrounding the tumor on a T2-weighted breast MRI. PE was qualitatively evaluated by three readers with more than 20 years of experience in interpreting breast field imaging findings. Residual cancer burden (RCB) were assessed post-NACT. Recurrence-free survival (RFS) and overall survival (OS) were evaluated as the endpoints of this study. STATISTICAL TESTS: Chi-square test; Kaplan-Meier method, log-rank test, and Cox proportional hazard model. A P-value <0.05 was considered statistically significant. RESULTS: Pre-PE was observed in 64 out of 128 patients. Of these, rPE was observed in 21. In the log-rank test, breast cancer with rPE had significantly worse RFS and OS than that without rPE. Cox proportional hazard analysis identified rPE as a significant prognostic factor for recurrence (hazard ratio, 11.6; 95% confidence interval [CI], 3.05-43.8) and death (hazard ratio, 17.8; 95% CI, 3.30-96.3). Breast cancer with rPE had significant worse RFS and OS than that without rPE in RCB class II, and significant worse OS in pathological complete response, class I and class II in the log-rank test. DATA CONCLUSION: rPE on a T2-weighted breast MRI was a significant factor for breast cancer recurrence and death in patients with pre-PE-positive breast cancer treated with NACT. TECHNICAL EFFICACY: Stage 2.

Demand analysis of health care services for community-dwelling breast cancer survivors based on the Kano model: A cross-sectional study.

Objectives: Providing satisfactory healthcare services for breast cancer survivors can effectively reduce their burden and the pressure on medical resources. The aim of this study was to explore health care service demands for community-dwelling breast cancer survivors using the Kano model. Methods: A cross-sectional survey was conducted from January to March 2023 among breast cancer survivors discharged from a tertiary cancer hospital. Participants were asked to fill out a self-designed questionnaire involving the Kano model, which helped to categorize and prioritize the attributes of healthcare services. The questionnaire included 30 health care services. Additionally, their social demographic characteristics were collected during the survey. Results: A total of 296 valid questionnaires were collected, and demand attributes of the 30 health care services were evaluated. The findings revealed that one of 30 services was classified as "must-be attributes" (body image management), 13 as "one-dimensional attributes" (focused on medical security support, health management, and health counseling), 3 as "attractive attributes" (focused on communication needs and telehealth services), and 11 as "indifferent attributes" (mainly in the area of psycho-social services). Conclusions: Breast cancer survivors in the community have different levels of need for various health care services. It's crucial for healthcare providers to identify these needs and devise effective strategies to deliver the appropriate services. Services with must-be and one-dimensional attributes should be given priority, and efforts should be made to provide services with attractive attributes, hence improving the quality of life of breast cancer survivors.

Financial toxicity, family resilience and negative emotions among young and middle-aged breast cancer patients: A multicentre cross-sectional study.

PURPOSE: To determine financial toxicity in young and middle-aged women with breast cancer and examine the associations between family resilience and negative emotions. METHODS: A multicentre cross-sectional study was conducted, 538 women with breast cancer were recruited from four hospitals. FT, family resilience, and negative emotions were collected using the Comprehensive Score for FT, the Chinese version of the Family Resilience Assessment in Breast Cancer Patients, Patient Health Questionnaire-9 item, and Generalized Anxiety Disorder-7. This study adhered to the STROBE guidelines. RESULTS: The valid response rate was 96.8 % (N = 521). Overall, the score for FT was 19.63 ± 10.13. FT was significantly correlated with family resilience (r = 0.30, p < 0.010) and depression (r = -0.11, p < 0.050). The hierarchical multiple linear regression analysis showed that career status, monthly income, religion, and family resilience were the main factors influencing FT in patients with breast cancer (R2 = 0.37; F = 6.83; p < 0.001). CONCLUSIONS: FT was more prevalent among women from low-income career. Women with poor family resilience, no religious also suffer greater financial toxicity. It is necessary to pay more attention of the financial toxicity of female' low-income career, no religious belief and poor family resilience. Developing effective interventions based on family resilience might be helpful in promoting their well-being.

Nomogram for preoperative differentiation of benign and malignant breast tumors using contrast-enhanced cone-beam breast CT (CE CB-BCT) quantitative imaging and assessment features.

PURPOSE: Breast cancer's impact necessitates refined diagnostic approaches. This study develops a nomogram using radiology quantitative features from contrast-enhanced cone-beam breast CT for accurate preoperative classification of benign and malignant breast tumors. MATERIAL AND METHODS: A retrospective study enrolled 234 females with breast tumors, split into training and test sets. Contrast-enhanced cone-beam breast CT-images were acquired using Koning Breast CT-1000. Quantitative assessment features were extracted via 3D-slicer software, identifying independent predictors. The nomogram was constructed to preoperative differentiation benign and malignant breast tumors. Calibration curve was used to assess whether the model showed favorable correspondence with pathological confirmation. Decision curve analysis confirmed the model's superiority. RESULTS: The study enrolled 234 female patients with a mean age of 50.2 years (SD ± 9.2). The training set had 164 patients (89 benign, 75 malignant), and the test set had 70 patients (29 benign, 41 malignant). The nomogram achieved excellent predictive performance in distinguishing benign and malignant breast lesions with an AUC of 0.940 (95% CI 0.900-0.940) in the training set and 0.970 (95% CI 0.940-0.970) in the test set. CONCLUSION: This study illustrates the effectiveness of quantitative radiology features derived from contrast-enhanced cone-beam breast CT in distinguishing between benign and malignant breast tumors. Incorporating these features into a nomogram-based diagnostic model allows for breast tumor diagnoses that are objective and possess good accuracy. The application of these insights could substantially increase reliability and efficacy in the management of breast tumors, offering enhanced diagnostic capability.

Multilevel contributors to racial and ethnic inequities in the resolution of abnormal mammography results.

PURPOSE: Multiple ecological levels influence racial inequities in the completion of diagnostic testing after receiving abnormal mammography results (diagnostic resolution). Yet, few studies examine more than two ecological levels. We investigated the contributions of county, imaging facility, and patient characteristics on our primary and secondary outcomes, the achievement of diagnostic resolution by (1)Black women and Latinas, and (2) the entire sample. We hypothesized that women of color would be less likely to achieve resolution than their White counterparts, and this relationship would be mediated by imaging facility features and moderated by county characteristics. METHODS: Records for 25,144 women with abnormal mammograms between 2011 and 2019 from the Carolina Mammography Registry were merged with publicly available county data. Diagnostic resolution was operationalized as the percentage of women achieving resolution within 60 days of receiving abnormal results and overall time to resolution and examined using mixed effects logistic regression and Cox proportional hazard models, respectively. RESULTS: Women of color with abnormal screening mammograms were less likely to achieve resolution within 60 days compared with White women (OR 0.83, CI 0.78-0.89; OR 0.74, CI.60-0.91, respectively) and displayed longer resolution times (HR 0.87, CI 0.84-0.91; HR 0.78, CI 0.68-0.89). Residential segregation had a moderating effect, with Black women in more segregated counties being less likely to achieve resolution by 60 days but lost statistical significance after adjustment. No mediators were discovered. CONCLUSION: More work is needed to understand how imaging center and community characteristics impact racial inequities in resolution and resolution in general.

Health utility values of breast cancer treatments and the impact of varying quality of life assumptions on cost-effectiveness.

In breast cancer research, utility assumptions are outdated and inconsistent which may affect the results of quality adjusted life year (QALY) calculations and thereby cost-effectiveness analyses (CEAs). Four hundred sixty four female patients with breast cancer treated at Erasmus MC, the Netherlands, completed EQ-5D-5L questionnaires from diagnosis throughout their treatment. Average utilities were calculated stratified by age and treatment. These utilities were applied in CEAs analysing 920 breast cancer screening policies differing in eligible ages and screening interval simulated by the MISCAN-Breast microsimulation model, using a willingness-to-pay threshold of €20,000. The CEAs included varying sets on normative, breast cancer treatment and screening and follow-up utilities. Efficiency frontiers were compared to assess the impact of the utility sets. The calculated average patient utilities were reduced at breast cancer diagnosis and 6 months after surgery and increased toward normative utilities 12 months after surgery. When using normative utility values of 1 in CEAs, QALYs were overestimated compared to using average gender and age-specific values. Only small differences in QALYs gained were seen when varying treatment utilities in CEAs. The CEAs varying screening and follow-up utilities showed only small changes in QALYs gained and the efficiency frontier. Throughout all variations in utility sets, the optimal strategy remained robust; biennial for ages 40-76 years and occasionally biennial 40-74 years. In sum, we recommend to use gender and age stratified normative utilities in CEAs, and patient-based breast cancer utilities stratified by age and treatment or disease stage. Furthermore, despite varying utilities, the optimal screening scenario seems very robust.

Women's attitudes and perspectives on the use of artificial intelligence in the assessment of screening mammograms.

PURPOSE: To investigate attitudes and perspectives on the use of artificial intelligence (AI) in the assessment of screening mammograms among women invited to BreastScreen Norway. METHOD: An anonymous survey was sent to all women invited to BreastScreen Norway during the study period, October 10, 2022, to December 25, 2022 (n = 84,543). Questions were answered on a 10-point Likert scale and as multiple-choice, addressing knowledge of AI, willingness to participate in AI studies, information needs, confidence in AI results and AI assisted reading strategies, and thoughts on concerns and benefits of AI in mammography screening. Analyses were performed using χ2 and logistic regression tests. RESULTS: General knowledge of AI was reported as extensive by 11.0% of the 8,355 respondents. Respondents were willing to participate in studies using AI either for decision support (64.0%) or triaging (54.9%). Being informed about use of AI-assisted image assessment was considered important, and a reading strategy of AI in combination with one radiologist preferred. Having extensive knowledge of AI was associated with willingness to participate in AI studies (decision support; odds ratio [OR]: 5.1, 95% confidence interval [CI]: 4.1-6.4, and triaging; OR: 3.4, 95% CI: 2.8-4.0) and trust in AI's independent assessment (OR: 6.8, 95% CI: 5.7, 8.3). CONCLUSIONS: Women invited to BreastScreen Norway had a positive attitude towards the use of AI in image assessment, given that human readers are still involved. Targeted information and increased public knowledge of AI could help achieve high participation in AI studies and successful implementation of AI in mammography screening.

Evolving paradigms in breast cancer screening: Balancing efficacy, personalization, and equity.

Breast cancer remains a significant global health challenge, with projections indicating a troubling increase in incidence. Breast cancer screening programs have long been hailed as life-saving initiatives, yet their true impact on mortality rates is a subject of ongoing debate. Screening poses the risk of false positives and the detection of indolent tumors, potentially leading to overtreatment. Bias factors, including lead time, length time, and selection biases, further complicate the assessment of screening efficacy. Recent studies suggest that AI-driven image analysis may revolutionize breast cancer screening, maintaining diagnostic accuracy while reducing radiologists' workload. However, the generalizability of these findings to diverse populations is a critical consideration. Personalized screening approaches and equitable access to advanced technologies are essential to mitigate disparities. In conclusion, the breast cancer screening landscape is evolving, emphasizing the need for risk stratification, appropriate imaging modalities, and a personalized approach to reduce overdiagnosis and focus on cancers with the potential to impact lives while prioritizing patient-centered care.

Awareness and Candidacy for Endocrine Prevention and Risk Reducing Mastectomy in Unaffected High-Risk Women Referred for Breast Cancer Risk Assessment.

INTRODUCTION: Primary prevention of breast cancer in women at elevated risk includes several strategies such as endocrine prevention and risk-reducing mastectomy (RRM). The objective of this study was to evaluate awareness of different preventive strategies across high-risk subgroups. PATIENTS AND METHODS: Women referred for high risk evaluation between 2020 and 2023 completed an initial risk-assessment questionnaire that included questions around perceived lifetime risk and consideration of preventive strategies. One-way analysis of variance (ANOVA) and chi-squared tests were used to compare differences across different high-risk subgroups. RESULTS: 482 women with a median age of 43 years (20-79 years) met inclusion criteria; 183 (38.0%) germline pathogenic variant carriers (GPV), 90 (18.7%) with high-risk lesions (HRL) on breast biopsy, and 209 (43.4%) with strong family history (FH) without a known genetic predisposition. Most high-risk women reported that they had considered increased screening and surveillance (83.7%) and lifestyle strategies (80.6%), while fewer patients had considered RRM (39.8%) and endocrine prevention (27.0%). Prior to initial consultation, RRM was more commonly considered in GPV carriers (59.4%) relative to those with HRL (33.3%) or strong FH (26.3%, p < 0.001). Based on current guidelines, 206 (43%) patients were deemed eligible for endocrine prevention, including 80.5% with HRL and 39.0% with strong FH. Prior consideration of endocrine prevention was highest in patients with HRL and significantly lower in those with strong FH (47.2% HRL versus 31.1% GPV versus 18.7% FH, p = 0.001). CONCLUSIONS: Endocrine prevention is the least considered preventive option for high-risk women, despite eligibility in a significant proportion of those presenting with HRL or strong FH.

A bimodal nomogram as an adjunct tool to reduce unnecessary breast biopsy following discordant ultrasonic and mammographic BI-RADS assessment.

OBJECTIVE: To develop a bimodal nomogram to reduce unnecessary biopsies in breast lesions with discordant ultrasound (US) and mammography (MG) Breast Imaging Reporting and Data System (BI-RADS) assessments. METHODS: This retrospective study enrolled 706 women following opportunistic screening or diagnosis with discordant US and MG BI-RADS assessments (where one assessed a lesion as BI-RADS 4 or 5, while the other assessed the same lesion as BI-RADS 0, 2, or 3) from two medical centres between June 2019 and June 2021. Univariable and multivariable logistic regression analyses were used to develop the nomogram. DeLong's and McNemar's tests were used to assess the model's performance. RESULTS: Age, MG features (margin, shape, and density in masses, suspicious calcifications, and architectural distortion), and US features (margin and shape in masses as well as calcifications) were independent risk factors for breast cancer. The nomogram obtained an area under the curve of 0.87 (95% confidence interval (CI), 0.83-0.91), 0.91 (95% CI, 0.87 - 0.96), and 0.92 (95% CI, 0.86-0.98) in the training, internal validation, and external testing samples, respectively, and demonstrated consistency in calibration curves. Coupling the nomogram with US reduced unnecessary biopsies from 74 to 44% and the missed malignancies rate from 13 to 2%. Similarly, coupling with MG reduced missed malignancies from 20 to 6%, and 63% of patients avoided unnecessary biopsies. Interobserver agreement between US and MG increased from - 0.708 (poor agreement) to 0.700 (substantial agreement) with the nomogram. CONCLUSION: When US and MG BI-RADS assessments are discordant, incorporating the nomogram may improve the diagnostic accuracy, avoid unnecessary breast biopsies, and minimise missed diagnoses. CLINICAL RELEVANCE STATEMENT: The nomogram developed in this study could be used as a computer program to assist radiologists with detecting breast cancer and ensuring more precise management and improved treatment decisions for breast lesions with discordant assessments in clinical practice. KEY POINTS: • Coupling the nomogram with US and mammography improves the detection of breast cancers without the risk of unnecessary biopsy or missed malignancies. • The nomogram increases mammography and US interobserver agreement and enhances the consistency of decision-making. • The nomogram has the potential to be a computer program to assist radiologists in identifying breast cancer and making optimal decisions.

Variation in State-Level Mammography Use, 2012 and 2020.

OBJECTIVES: Mammography is a screening tool for early detection of breast cancer. Uptake in screening use in states can be influenced by Medicaid coverage and eligibility policies, public health outreach efforts, and the Centers for Disease Control and Prevention-funded National Breast and Cervical Cancer Early Detection Program. We described state-specific mammography use in 2020 and changes as compared with 2012. METHODS: We estimated the proportion of women aged ≥40 years who reported receiving a mammogram in the past 2 years, by age group, state, and demographic and socioeconomic characteristics, using 2020 Behavioral Risk Factor Surveillance System data. We also compared 2020 state estimates with 2012 estimates. RESULTS: The proportion of women aged 50-74 years who received a mammogram in the past 2 years was 78.1% (95% CI, 77.4%-78.8%) in 2020. Across measures of socioeconomic status, mammography use was generally lower among women who did not have health insurance (52.0%; 95% CI, 48.3%-55.6%) than among those who did (79.9%; 95% CI, 79.3%-80.6%) and among those who had a usual source of care (49.4%; 95% CI, 46.1%-52.7%) than among those who did not (81.0%; 95% CI, 80.4%-81.7%). Among women aged 50-74 years, mammography use varied across states, from a low of 65.2% (95% CI, 61.4%-69.0%) in Wyoming to a high of 86.1% (95% CI, 83.8%-88.3%) in Massachusetts. Four states had significant increases in mammography use from 2012 to 2020, and 8 states had significant declines. CONCLUSION: Mammography use varied widely among states. Use of evidence-based interventions tailored to the needs of local populations and communities may help close gaps in the use of mammography.

Assessment of whole-body MRI including diffusion-weighted sequences in the initial staging of breast cancer patients at high risk of metastases in comparison with PET-CT: a prospective cohort study.

OBJECTIVE: The aim of this study was to assess the diffusion-weighted whole-body-MRI (WBMRI) in the initial staging of breast cancer at high risk of metastases in comparison with positron emission tomography (PET)-CT. METHODS: Forty-five women were prospectively enrolled. The inclusion criteria were female gender, age >18, invasive breast cancer, an initial PET-CT, and a performance status of 0-2. The exclusion criteria were contraindication to WB-MRI and breast cancer recurrence. The primary outcome was the concordance of WB-MRI and PET-CT in the diagnosis of distant metastases, whereas secondary outcomes included their concordance for the primary tumor and regional lymph nodes (LN), as well as the agreement of WB-MRI interpretation between two radiologists. RESULTS: The mean age was 51.2 years with a median size of the primary tumor of 30 mm. Concordance between the two modalities was almost perfect for metastases staging, all sites included (k = 0.862), with excellent interobserver agreement. The accuracy of WB-MRI for detecting regional LN, distant LN, lung, liver, or bone metastases ranged from 91 to 96%. In 2 patients, WB-MRI detected bone metastases that were overlooked by PET-CT. WB-MRI showed a substantial agreement with PET-CT for staging the primary tumor, regional LN status, and stage (k = 0.766, k = 0.756, and k = 0.785, respectively) with a high interobserver agreement. CONCLUSION: WB-MRI including DWI could be a reliable and reproducible examination in the initial staging of breast cancer patients at high risk of metastases, especially for bone metastases and therefore could be used as a surrogate to PET-CT. CLINICAL RELEVANCE STATEMENT: Whole-body-MRI including DWI is a promising technique for detecting metastases in the initial staging of breast cancer at high risk of metastases. KEY POINTS: Whole-body-MRI (WB-MRI) was effective for detecting metastases in the initial staging of 45 breast cancer patients at high risk of metastases in comparison with PET-CT. Concordance between WB-MRI and PET-CT was almost perfect for metastases staging, all sites included, with excellent interobserver agreement. The accuracy of WB-MRI for detecting bone metastases was 92%.

Breast Cancer Screening in Georgia: Choosing the Most Optimal and Cost-Effective Strategy.

OBJECTIVES: To define the optimal and cost-effective breast cancer screening strategy for Georgia. METHODS: We used the Microsimulation Screening Analysis-Breast (MISCAN-Breast) model that has been adapted to the Georgian situation to evaluate 736 mammography screening strategies varied by interval (biennial and triennial), starting ages (40-60 years), stopping ages (64-84 years), and screening modality (with and without clinical breast examination [CBE]). Quality-adjusted life-years (QALYs) and additional cost (healthcare perspective) compared with no screening per 1000 women were calculated with 3% discount. Major uncertainties (eg, costs) are addressed as sensitivity analyses. RESULTS: Strategies using a combination of mammography and CBE yielded in substantially higher costs with minimal differences in outcomes compared with mammography-only strategies. The current screening strategy, biennial mammography screening from the age of 40 until 70 years with CBE, is close to the frontier line but requires high additional cost given the QALY gains (€16 218/QALY), well above the willingness-to-pay threshold of €12 720. The optimal strategy in Georgia would be triennial mammography-only screening from age 45 to 66 years with an incremental cost-effectiveness ratio of €12 507. CONCLUSIONS: Biennial screening strategies are resource-intensive strategies and may not be feasible for Georgia. By switching to triennial mammography-only strategy from the age of 45 until 66 years, it is possible to offer screening to more eligible women while still gaining substantial screening benefits. This is to address capacity issues which is a common barrier for many Eastern European countries.

Medical care costs according to the stage and subtype of breast cancer in a municipal setting: a case study of Hachioji City, Japan.

BACKGROUND: It is important to assess whether the early detection of breast cancer affects medical care costs. However, research remains scant on the actual medical care costs associated with breast cancer treatment in Japan. This study aimed to determine the medical care costs of breast cancer treatment based on its stage using national health insurance claims data. METHODS: This was an observational study including patients with breast cancer who had undergone breast cancer treatment, as defined by the disease name and related treatment codes. Between August 2013 and June 2016, patients who underwent surgical treatment without axillary lymph node dissection and other radical treatment were classified as the curable group, while those who underwent palliative treatment were classified as the non-curable group. Patients were further stratified by subtype. The total and treatment-specific medical care costs for the five years were calculated using the national health insurance claims data of Hachioji City between August 2013 and May 2021. RESULTS: The mean total medical care costs for the curable and non-curable groups for the 5 years were JPY 3958 thousand (standard deviation 2664) and JPY 8289 thousand (8482), respectively. The mean medical care costs for specific breast cancer treatment for the curable and non-curable groups were JPY 1142 (728) thousand and JPY 3651 thousand (5337), respectively. Further, human epidermal growth factor receptor 2 + , Hormone + patients had the highest mean cost over the 5 years. CONCLUSIONS: The results suggest that the early detection of breast cancer may reduce medical care costs at the patient level.

Factors affecting the economic burden of breast cancer in southern Iran.

BACKGROUND: Breast cancer (BC) is the most common cancer in the world, and is associated with significant economic costs for patients and communities. Therefore, the information on the costs of the disease and the identification of its underlying factors will provide insights into designing effective interventions and reducing the costs. Thus, the present study aimed to identify the factors affecting the economic burden of breast cancer from all medical centers providing diagnostic and treatment services in southern Iran. METHODS: A list of factors affecting the economic burden of breast cancer was obtained based on the effective factors searched in the databases, including PubMed, ProQuest, Scopus, ISI Web of Science, SID, and Magiran, and the opinions of BC cancer specialists. Then, the data on 460 breast cancer patients was collected from March 2020 to March 2022. The relationship between the factors affecting Breast Cancer costs was analyzed using SPSS 13.0 software by the use of multiple regression analysis. RESULTS: The results of the multiple regression analysis showed that stages (P-value < 0.001), being an extreme user (p = 0.025), type of treatment center (P-value < 0.001), income (P-value < 0.001), chemotherapy side effects (P-value < 0.001), and distance to the nearest health center (P-value < 0.001) were important factors affecting the costs of breast cancer patients. CONCLUSIONS: According to the results, encouraging people to undergo annual screenings, increasing insurance coverage, assuring the patients about the desirability and adequacy of the provided medical services, deploying specialists in chemotherapy centers (especially nutritionists) to recommend special diets, and establishing cancer diagnostic and treatment centers in high-population cities could help reduce the costs of breast cancer patients.

One versus three weeks hypofractionated whole breast radiotherapy for early breast cancer treatment: the FAST-Forward phase III RCT.

Background: FAST-Forward aimed to identify a 5-fraction schedule of adjuvant radiotherapy delivered in 1 week that was non-inferior in terms of local cancer control and as safe as the standard 15-fraction regimen after primary surgery for early breast cancer. Published acute toxicity and 5-year results are presented here with other aspects of the trial. Design: Multicentre phase III non-inferiority trial. Patients with invasive carcinoma of the breast (pT1-3pN0-1M0) after breast conservation surgery or mastectomy randomised (1 : 1 : 1) to 40 Gy in 15 fractions (3 weeks), 27 Gy or 26 Gy in 5 fractions (1 week) whole breast/chest wall (Main Trial). Primary endpoint was ipsilateral breast tumour relapse; assuming 2% 5-year incidence for 40 Gy, non-inferiority pre-defined as < 1.6% excess for 5-fraction schedules (critical hazard ratio = 1.81). Normal tissue effects were assessed independently by clinicians, patients and photographs. Sub-studies: Two acute skin toxicity sub-studies were undertaken to confirm safety of the test schedules. Primary endpoint was proportion of patients with grade ≥ 3 acute breast skin toxicity at any time from the start of radiotherapy to 4 weeks after completion. Nodal Sub-Study patients had breast/chest wall plus axillary radiotherapy testing the same three schedules, reduced to the 40 and 26 Gy groups on amendment, with the primary endpoint of 5-year patient-reported arm/hand swelling. Limitations: A sequential hypofractionated or simultaneous integrated boost has not been studied. Participants: Ninety-seven UK centres recruited 4096 patients (1361:40 Gy, 1367:27 Gy, 1368:26 Gy) into the Main Trial from November 2011 to June 2014. The Nodal Sub-Study recruited an additional 469 patients from 50 UK centres. One hundred and ninety and 162 Main Trial patients were included in the acute toxicity sub-studies. Results: Acute toxicity sub-studies evaluable patients: (1) acute grade 3 Radiation Therapy Oncology Group toxicity reported in 40 Gy/15 fractions 6/44 (13.6%); 27 Gy/5 fractions 5/51 (9.8%); 26 Gy/5 fractions 3/52 (5.8%). (2) Grade 3 common toxicity criteria for adverse effects toxicity reported for one patient. At 71-month median follow-up in the Main Trial, 79 ipsilateral breast tumour relapse events (40 Gy: 31, 27 Gy: 27, 26 Gy: 21); hazard ratios (95% confidence interval) versus 40 Gy were 27 Gy: 0.86 (0.51 to 1.44), 26 Gy: 0.67 (0.38 to 1.16). With 2.1% (1.4 to 3.1) 5-year incidence ipsilateral breast tumour relapse after 40 Gy, estimated absolute differences versus 40 Gy (non-inferiority test) were -0.3% (-1.0-0.9) for 27 Gy (p = 0.0022) and -0.7% (-1.3-0.3) for 26 Gy (p = 0.00019). Five-year prevalence of any clinician-assessed moderate/marked breast normal tissue effects was 40 Gy: 98/986 (9.9%), 27 Gy: 155/1005 (15.4%), 26 Gy: 121/1020 (11.9%). Across all clinician assessments from 1 to 5 years, odds ratios versus 40 Gy were 1.55 (1.32 to 1.83; p < 0.0001) for 27 Gy and 1.12 (0.94-1.34; p = 0.20) for 26 Gy. Patient and photographic assessments showed higher normal tissue effects risk for 27 Gy versus 40 Gy but not for 26 Gy. Nodal Sub-Study reported no arm/hand swelling in 80% and 77% in 40 Gy and 26 Gy at baseline, and 73% and 76% at 24 months. The prevalence of moderate/marked arm/hand swelling at 24 months was 10% versus 7% for 40 Gy compared with 26 Gy. Interpretation: Five-year local tumour incidence and normal tissue effects prevalence show 26 Gy in 5 fractions in 1 week is a safe and effective alternative to 40 Gy in 15 fractions for patients prescribed adjuvant local radiotherapy after primary surgery for early-stage breast cancer. Future work: Ten-year Main Trial follow-up is essential. Inclusion in hypofractionation meta-analysis ongoing. A future hypofractionated boost trial is strongly supported. Trial registration: FAST-Forward was sponsored by The Institute of Cancer Research and was registered as ISRCTN19906132. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 09/01/47) and is published in full in Health Technology Assessment; Vol. 27, No. 25. See the NIHR Funding and Awards website for further award information.

Patients diagnosed with early breast cancer are often recommended to have radiotherapy after surgery because research has shown that it lowers the risk of the cancer returning. However, it may cause some short- and long-term side effects. Previous clinical trials showed that the same, or even better, outcomes with a lower total dose of radiotherapy given in fewer, larger daily doses compared with older historical treatment schedules. The National Institute for Health and Care Research Health Technology Assessment Programme-funded FAST-Forward Trial aimed to see whether the number of doses could be reduced further without reducing the beneficial effects of radiotherapy. Between November 2011 and June 2014, 4096 patients agreed to take part in the FAST-Forward Main Trial testing three schedules of radiotherapy to the breast. Standard treatment given on 15 days over 3 weeks (Control Group) was compared with two different lower dose schedules where treatment was given on 5 days over 1 week (lower dose Test Groups). An additional 469 patients entered a sub-study where the gland area under the arm also received radiotherapy (Nodal Sub-Study). Main Trial 5-year results reported in April 2020 showed that the number of patients whose cancer had returned in the treated breast was low in all groups: around 2 in 100 (2.1%) for the Control Group, and 1.7% in the higher dose and 1.4% in the lower dose Test Groups. The majority of reported side effects assessed by patients and doctors up to 5 years after radiotherapy were mild for all treatment groups. Patients in the Control Group and in the lower dose Test Group experienced similar levels of side effects. More side effects were reported in the higher dose Test Group, although differences were small. Overall, the FAST-Forward findings suggest that the lower dose 1-week schedule gave similar results in terms of the cancer returning and side effects to the standard 3-week treatment and this schedule can now be used to help treat future patients.

Accuracy of Ex-vivo Fluorescence Confocal Microscopy in Margin Assessment of Solid Tumors: A Systematic Review.

Fluorescence confocal microscopy (FCM) is a novel technology that enables rapid high-resolution digital imaging of non-formalin-fixed tissue specimens and offers real-time positive surgical margin identification. In this systematic review, we evaluated the accuracy metrics of ex vivo FCM for intraoperative margin assessment of different tumor types. A systematic search of MEDLINE via PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus was performed for relevant papers (PROSPERO ID: CRD42022372558). We included 14 studies evaluating four types of microscopes in six different tumor types, including breast, prostate, central nervous system, kidney, bladder, and conjunctival tumors. Using the Quality Assessment of Diagnostic Accuracy Studies tool, we identified a high risk of bias in patient selection (21%) and index test (36%) of the included studies. Overall, we found that FCM has good accuracy metrics in all tumor types, with high sensitivity and specificity (>80%) and almost perfect concordance (>90%) against final pathology results. Despite these promising findings, the quality of the available evidence and bias concerns highlight the need for adequately designed studies to further define the role of ex vivo FCM in replacing the frozen section as the tool of choice for intraoperative margin assessment.

Temporal Evolution and Associated Factors of Adherence to Mammography Screening among Women in Spain: Results from Two National Health Surveys (2017-2020).

Ensuring equity in cancer screening is recommended by the European Commission. Despite the fact that breast cancer screening is a free population-based program in Spain, there remains considerable variation in the adherence to screening rate among population groups. This study was designed to describe the adherence of breast cancer screening in women in Spain, to evaluate the evolution in the period from 2017 to 2020, and to determine the variables that influence choosing to undergo breast cancer screening. A nationwide cross-sectional study with 7220 females aged 50-69 years from the 2017 Spanish National Health Survey and the 2020 European Health Survey for Spain was performed. We investigated mammography uptake rates, with socio-demographic factors, lifestyle habits, and health-related characteristics as independent variables. Multivariable logistic regression was used to identify the associated factors of mammography adherence. Of the women, 78% had undergone mammography in the previous two years, and there was a significant decrease in the uptake rate for breast cancer screening from 2017 (81.23%) to 2020 (74.68%) (p < 0.001). Educational level, marital status, residential location, nationality, smoking status, alcohol consumption, and leisure-time physical activity were all associated factors of mammography uptake.

MRI Assessment of Changes in Tumor Vascularization during Neoadjuvant Anti-Angiogenic Treatment in Locally Advanced Breast Cancer Patients.

Anti-VEGF (vascular endothelial growth factor) treatment improves response rates, but not progression-free or overall survival in advanced breast cancer. It has been suggested that subgroups of patients may benefit from this treatment; however, the effects of adding anti-VEGF treatment to a standard chemotherapy regimen in breast cancer patients are not well studied. Understanding the effects of the anti-vascular treatment on tumor vasculature may provide a selection of patients that can benefit. The aim of this study was to study the vascular effect of bevacizumab using clinical dynamic contrast-enhanced MRI (DCE-MRI). A total of 70 women were randomized to receive either chemotherapy alone or chemotherapy with bevacizumab for 25 weeks. DCE-MRI was performed at baseline and at 12 and 25 weeks, and in addition 25 of 70 patients agreed to participate in an early MRI after one week. Voxel-wise pharmacokinetic analysis was performed using semi-quantitative methods and the extended Tofts model. Vascular architecture was assessed by calculating the fractal dimension of the contrast-enhanced images. Changes during treatment were compared with baseline and between the treatment groups. There was no significant difference in tumor volume at any point; however, DCE-MRI parameters revealed differences in vascular function and vessel architecture. Adding bevacizumab to chemotherapy led to a pronounced reduction in vascular DCE-MRI parameters, indicating decreased vascularity. At 12 and 25 weeks, the difference between the treatment groups is severely reduced.