Breast Cancer Morbidity Research Articles

Analysis of the morbidity of breast cancer in Ukraine and the city of Kyiv

One of the main causes of mortality worldwide is malignant neoplasms, and in Ukraine, breast cancer ranks first among all cancer diseases and mortality among women. With the help of official epidemiological data, it is possible to estimate the level and forecast the costs of the prevention and treatment of breast cancer in women.
 The purpose of the study was to analyze epidemiological indicators of breast cancer incidence and mortality among the female population in Ukraine and the city of Kyiv.
 The study used data on the incidence and mortality from breast cancer in women of the National Cancer Registry of Ukraine for 2011–2021. Analytical-comparative, epidemiological, graphic, and mathematical-statistical methods were used.
 The results of the analysis of epidemiological indicators showed that the largest number of sick women was registered in 2012 – 17,746, and the smallest in 2020 – 12,736. The highest growth rate of the chain coefficient of decrease/increase in the incidence and mortality rate of breast cancer in women was in 2015 – 23% and 8%, respectively. The lowest number of registered cases of breast cancer for 2016–2020 in Ukraine is observed in the Western region, and the largest in the Northern region. The highest mortality rate was recorded in women in the city of Kyiv and in Ukraine as a whole from breast cancer in 2012 (18.2 and 16.9 per 100,000 population, respectively). In general, the mortality trend in the city of Kyiv is higher than in Ukraine. The results of the analysis showed that breast cancer is most often detected for the first time at the I–II stage of the disease. The largest number of such patients was found in Ukraine in 2015 – 78.6% of the total number of cases.
 Taking into account the analyzed epidemiological data on the incidence and mortality of women from breast cancer in Ukraine and the city of Kyiv, it is necessary to conduct social programs for early screening of breast cancer at the state level and provide such patients with effective anticancer drugs at all stages of treatment.

Artificial Intelligence Applications in Breast Imaging: Current Status and Future Directions.

Attempts to use computers to aid in the detection of breast malignancies date back more than 20 years. Despite significant interest and investment, this has historically led to minimal or no significant improvement in performance and outcomes with traditional computer-aided detection. However, recent advances in artificial intelligence and machine learning are now starting to deliver on the promise of improved performance. There are at present more than 20 FDA-approved AI applications for breast imaging, but adoption and utilization are widely variable and low overall. Breast imaging is unique and has aspects that create both opportunities and challenges for AI development and implementation. Breast cancer screening programs worldwide rely on screening mammography to reduce the morbidity and mortality of breast cancer, and many of the most exciting research projects and available AI applications focus on cancer detection for mammography. There are, however, multiple additional potential applications for AI in breast imaging, including decision support, risk assessment, breast density quantitation, workflow and triage, quality evaluation, response to neoadjuvant chemotherapy assessment, and image enhancement. In this review the current status, availability, and future directions of investigation of these applications are discussed, as well as the opportunities and barriers to more widespread utilization.

G-protein-coupled receptor 141 mediates breast cancer proliferation and metastasis by regulating oncogenic mediators and the p-mTOR/p53 axis.

Breast cancer morbidity is surging towards the peak in females across the globe. An inherent property of cancer cells is enhanced cell proliferation rate and migration capability, leading to deregulated cell signaling cascades. G-protein-coupled receptors (GPCRs) have recently emerged as a hot-spot target in cancer research. We identify aberrant expression of G-protein-coupled receptor 141 (GPR141) in different breast cancer subtypes that correlate with poor prognosis. However, the molecular mechanism via which GPR141 advances breast cancer remains elusive. Increased GPR141 expression enhances the migratory behavior of breast cancer, driving oncogenic pathways both in vitro and in vivo through activation of epithelial to mesenchymal transition (EMT), oncogenic mediators and regulation of p-mTOR/p53 signaling. Our study unveils a molecular mechanism for p53 downregulation and activation of p-mTOR1 and its substrates in GPR141 overexpressed cells, accelerating breast tumorigenesis. We find that an E3 ubiquitin ligase, Cullin1, partly mediates p53 degradation via proteasomal pathway. Co-immunoprecipitation result shows that the phosphorylated form of 40S ribosome protein S6 (ps6., a p-mTOR1 substrate) forms a complex with Cullin1. These findings suggest an interplay between Cullin1 and p-mTOR1 in GPR141 overexpressed cells that downregulates p53 expression, thus inducing tumor growth. GPR141 silencing restores p53 expression and attenuates p-mTOR1 signaling events, thereby impeding proliferation and migration in breast cancer cells. Our findings describe the role of GPR141 in breast cancer proliferation, and metastasis, as well as in influencing the tumor microenvironment. Modulating GPR141 expression could pave the way for a better therapeutic approach to regulating breast cancer progression and metastasis.

A new population screening program for BRCA mutations in Israel – Attitudes and barriers among Ashkenazi Jewish women

Israeli Jewish women of Ashkenazi ancestry have a high BRCA mutation carrier rate. Therefore, recently, Israel included free genetic testing among all Jewish women with Ashkenazi ancestry, 25 yrs. and older in its public health system. The aim of this study was to assess the intention of eligible women to be tested for BRCA mutations, and to find factors that may affect their decision. We distributed an online survey to a panel of participants in a commercial research institute. The survey included socio-demographic characteristics, attitudes towards preventive actions, views related to benefits and limitations of performing the BRCA test, worry regarding cancer morbidity, knowledge about breast cancer morbidity and hereditary breast cancer genetics. The survey concluded with a question regarding the woman’s interest in undergoing the BRCA test. The results showed that among the 506 respondents, 250 (49%) were interested in BRCA testing, 42 (8%) objected and 214 (43%) were undecided. In comparing the undecided to the other groups, we found that most presented a positive attitude towards screening tests and preventive medicine, they showed acceptable knowledge about the proposed test, and yet were interested in learning and further expanding the knowledge and the consequences of doing the test. Most respondents of all groups expressed concern of breast cancer morbidity and were reluctant to perform the test for reasons of reducing uncertainty, implications for children and implications for their own health. Within all groups, many women expressed their desire to consult with a medical professional about the test. We conclude that aiming to improve the performance of BRCA genetic testing, women need a thorough explanation about its implications. The main way to inform them would be by medical professionals, especially in primary care. This implies that front line nurses and physicians need to become more knowledgeable and committed to this subject.

Comparison of serum metabolomics in women with breast Cancer Prior to Chemotherapy and at 1 year: cardiometabolic implications

ObjectiveEarly-stage breast cancer (BC) is the second most common malignancy in women, worldwide. Early-detection and treatment advances have led to 5-year survival rates of 90% for early-stage breast cancer. However, the long-term morbidity of breast cancer remains high, with a majority of survivors facing increased risk of cardiometabolic conditions as well as secondary cancers. In particular, African American women with breast cancer experience higher morbidity and mortality than other women. Metabolomics is the comprehensive study of metabolites in biological samples to elucidate the role of monosaccharides, amino acids, and their respective metabolic pathways. Although some studies have found differential metabolites in women with breast cancer compared to normal controls, there has been little study of women with breast cancer across time and the active treatment trajectory. This study examines and compares the serum metabolomic profile of women with BC, prior to initial chemotherapy and at 1 year after inception of chemotherapy.MethodsThis study examined serum metabolites through a secondary analysis of a longitudinal parent study (EPIGEN) of women diagnosed with early-stage BC. Participants were evaluated across 5 time points: prior to their receipt of chemotherapy (T1), at the time of their 4th chemotherapy treatment (T2), 6 months after the initiation of chemotherapy (T3), one year after the initiation of chemotherapy (T4) and two years after the initiation of chemotherapy (T5). This analysis focused on the metabolomic data from 70 participants from T1 to T4. Using ultra high-pressure liquid chromatography high resolution mass spectrometry (UHPLC-HRMS), we performed Friedman Rank Sum Test followed by Nemenyi post-hoc pairwise tests to identify which metabolite levels differed between time points, focusing on metabolites with a Benjamini-Hochberg false discovery rate (FDR) from the overall Friedman test < 0.05 and then specifically examined the p-values from the T1 vs. T4 pairwise comparison.ResultsThe untargeted serum metabolomics yielded a total of 2,395 metabolites identified on the basis of the accurate mass and MS/MS fragmentation, 1,264 of which were significant after Friedman’s test (FDR < 0.05). The analysis then focused on the levels of 124 metabolites from the T1 vs. T4 post-hoc comparison that had a combined FDR < 0.05 and fold change (FC) > 2.0. Metabolite set enrichment analysis (MSEA) as part of Metaboanalyst 3.0 was performed to identify pathways that were significantly altered. The known metabolites identified from the functional analysis were used to evaluate the up and down regulated pathways. The 40metabolites from the Functional Analysis were mainly attributed to amino acids (specifically lysine regulation), fatty acids (particularly unsaturated) and steroid hormone synthesis (lysophosphatidic acid).ConclusionThere were multiple significant changes in the serum metabolomic profile of women with breast cancer at one-year post inception of chemotherapy compared to pre-chemotherapy, most notably associated with lysine degradation, branched-chain amino acid synthesis, linoleic acid metabolism, tyrosine metabolism and biosynthesis of unsaturated fatty acids as the top 5 metabolic pathways. Some of these changes could be associated with metabolic perturbations that are consistent with heightened risk of cardiometabolic morbidity. Our results provide new insights into the mechanisms underlying potential heightened cardiovascular health risks in this population.

Clinicopathological features and prognoses of very young patients (≤35 years) with breast cancer: a retrospective population-based study in China.

Clinicopathological features and prognoses of very young patients (≤35 years) with breast cancer: a retrospective population-based study in China.

Disaggregating the effects of daytime and nighttime light exposures on obesity, overweight, prostate and breast cancer morbidity worldwide

ABSTRACT Hormone-dependent cancers and overweight/obesity are not necessarily linked but might have similar underlying causes, such as circadian disruption, lack of physical activity, and unhealthy nutrition. Several empirical studies also attribute the rise in these types of morbidity to vitamin D deficiency, linked in turn to insufficient sunlight exposure. Other studies place an emphasis on melatonin (MLT) hormone suppression, associated with artificial light at night (ALAN) exposure. Yet no studies, carried out to date, have attempted to determine which of these environmental risk factors is associated stronger with the morbidity types in question. In this study, we aim to narrow this knowledge gap by analyzing data available for 100+ countries worldwide, while controlling ALAN and solar radiation exposure estimates by several potential confounders, such as GDPpc, GINI inequality index and unhealthy food consumption. As the study reveals, all the morbidity types under analysis are significantly and positively associated with ALAN exposure estimates (p < 0.05), while solar radiation appears to be significantly associated with prostate cancer rates only (p < 0.05), but not with breast cancer or overweight/obesity rates (p > 0.1). To the best of our knowledge, this study is the first that separates the effects of ALAN and daylight exposures on the abovementioned types of morbidity.

The Assessment and Comparison of the Knowledge of Breast Self-Examination and Breast Carcinoma Among Health Care Workers and the General Population in an Urban Setting.

Background Breast cancer is one of the common causes of cancer related mortality in women. Early detection and treatment can combat the morbidity and mortality of breast cancer. Most first-world countries have a screening program to facilitate early detection of breast malignancy. A lack of similar programs in developing countries, compounded with ignorance and financial crunch, often leaves women vulnerable due to late detection and complications. Identification of early physical changes in breasts through regular breast self-examination (BSE) can potentially aid in the early detection of breast lumps. Ideally, all women should have access to screening programs, although, practically, it is difficult to achieve mass screening in resource-poor areas. BSE cannot completely bridge this gap in health care; however, it can undoubtedly aid in increased awareness, identification of danger signs, and timely approach to the health care center for intervention. Materials and method A cross-sectional study was conducted at Bharati Vidyapeeth Medical College, Pune, India. The participants were administered a pretested questionnaire to collect information about their understanding of BSE. The data were analyzed using the Statistical Package for Social Sciences (SPSS) statistical software, Version 25. Mean and frequencies were used to compare participants from various backgrounds. Results The total sample consisted of 1,649 women from various educational backgrounds. Every doctor had heard about BSE compared to 81% of women from the general population; 84% of doctors and less than 40% of women representing the general population were taught to perform BSE; however, only around 34% of all women perform BSE. Women from the general population were largely unaware of the correct age to begin BSE, the frequency of performance, its correlation with the menstrual cycle, and the steps necessary to perform it. Women employed in the health care industry were better informed than the general population but still needed to be aware of BSE's details. Conclusion The study highlighted the lack of information regarding breast malignancy and self-examination among women from all educational and professional backgrounds. Women in the health care sector are better informed about the topic than the general population but still lack adequate information. There is a dire need to train women about the procedure, frequency, and correct time of conducting BSE and the telltale signs of breast carcinoma. Women in the health care industry can be educated and trained as educators on the topic, who can further disseminate the information to the general population to promote early detection of breast malignancy.

THE IMPLICATION OF GENETIC MEDICINE IN BREAST CANCER THERAPY IN NIGERIA: CLINICAL PRACTICE AND RESEARCH

In the preceding three decades, breast cancer occurrence and mortality rates have proliferated in Nigeria. Despite the considerable health, socioeconomic and developmental burdens breast cancer imposes on Nigeria, researchers have not extensively explored the use of genetic medicine in the management of this disease in Nigerian patients. This review’s objectives were to compare the diagnosis, treatment, and research of breast cancer in Nigeria and other countries. In addition, it also highlighted the setbacks and difficulties in breast cancer management in Nigeria. This journal employs a literature review. Detailed relevant articles were researched in two main electronic databases - Google Scholar and PubMed. The databases were analysed for keywords including: “breast cancer,” “breast cancer therapy,” “breast cancer diagnosis,” “breast cancer in Nigeria,” and “genetic medicine in breast cancer.” Only journals written in the English language between 1998 and 2022 were considered. 34 journals were identified, of which 22 were used for this review. Findings showed that genetics is not often considered for predicting and treating breast cancer. They also show that due to late presentation at the hospital, triple-negative breast cancer, usually at stage III or IV, is the most common breast cancer type in Nigeria. Genetic medicine should be integrated into the therapy and management of breast cancer in Nigeria. It will allow prediction of the disease, and timely diagnosis and ultimately possibly lead to a decline in breast cancer mortality and morbidity, just like in developed countries (high-income countries) such as The United States of America, Canada, and Sweden.

Abstract P2-02-03: Efficacy and Safety of the Addition of Internal Mammary Irradiation to Standard Adjuvant Radiation in Early-Stage Breast Cancer: A Systematic Review and Meta-analysis

Abstract Background: Adjuvant regional nodal irradiation together with whole breast or chest wall irradiation is considered standard of care in most node positive early breast cancer. Existing data on adding internal mammary irradiation (IMNI) to the regional nodal fields are inconsistent. The objective of this study was to conduct a meta-analysis to explore the efficacy and safety of adding IMNI to adjuvant radiotherapy in early-stage, high risk breast cancer. Methods: A search of PubMed and EMBASE identified randomized trials that investigated the addition of IMNI to standard adjuvant radiation in early-stage breast cancer. Hazard ratios (HRs) and 95% confidence intervals (CI) were extracted for overall survival (OS), breast cancer specific survival (BCSS), disease-free survival (DFS) and distant-metastasis free survival (DMFS). The odds ratios (ORs) for regional and loco-regional recurrence, non-breast cancer mortality, secondary non-breast cancer, contralateral breast cancer and cardiovascular morbidity and mortality were also extracted. These data where pooled in a meta-analysis using RevMan 5.4. Results: Analysis included 5 trials comprising 10,994 patients. Compared to the control group, IMNI was associated with a small, but statistically significant improvement in OS (HR=0.91, 95% 0.85-0.97, p=0.004), BCSS (HR=0.84, 95%0.77-0.92, p&amp;lt; 0.001), DFS (HR=0.89, 95% CI 0.82-0.98, p= 0.01) and DMFS (HR=0.89, 95% 0.81-0.98, p=0.02). IMNI was also associated with reduced odds for regional (OR=0.58, 95% 0.44-0.75, p&amp;lt; 0.001) and loco-regional recurrence (OR=0.85, 95% CI 0.72-1.00, p=0.04). Subgroup analyses for OS by tumor location (medial/central vs. lateral) and by nodal burden showed similar benefit is all subgroups. The odds for cardiotoxicity were higher, but did not reach statistical significance (OR=1.23, 95% 0.99-1.53, p=0.07). There was no association with cardiovascular mortality (OR=1.00, 95% 0.69-1.46, p=1.00). There were also comparable odds for non-breast cancer mortality (OR=1.05, 95% 0.79-1.41, p=0.74), secondary cancer (OR=0.95, 95% 0.82-1.10, p=0.51) and contra-lateral breast cancer (OR=1.07, 95% 0.77-1.51, p=0.68). Conclusions: Compared to the control group the addition of IMNI in high-risk patients is associated with a statistically significant improvement in survival, albeit with a magnitude of questionable clinical meaningfulness. Non-significant association with increased cardiovascular toxicity requires further study in longer-term studies. Citation Format: Yasmin Korzets, Dina Levitas, Ahuva Grubstein, Ben W Corn, Eitan Amir, Hadar Goldvaser. Efficacy and Safety of the Addition of Internal Mammary Irradiation to Standard Adjuvant Radiation in Early-Stage Breast Cancer: A Systematic Review and Meta-analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-02-03.

Myocardial Infarction-Induced INSL6 Decrease Contributes to Breast Cancer Progression.

Myocardial infarction (MI) induces early-stage breast cancer progression and increases breast cancer patients' mortality and morbidity. Insulin-like peptide 6 (INSL6) overexpression can impede cardiotoxin-induced injury through myofiber regeneration, playing a significant role in MI progression. To investigate the diverse significance of INSL6 in a variety of malignant tumors, we explored INSL6 through MI GEO dataset and multiple omics data integrative analysis, such as gene expression level, enriched pathway analysis, protein-protein interaction (PPI) analysis, and immune subtypes as well as diagnostic value and prognostic value in pancancer. INSL6 expression was downregulated in the MI group, and overall survival analysis demonstrated that INSL6 could be the prognostic biomarkers in the overall survival of breast cancer (BRCA). INSL6 expression differs significantly not only in most cancers but also in different molecular and immune subtypes of cancers. INSL6 might be a potential diagnostic and prognostic biomarker of cancers due to the high accuracy in diagnostic and prognostic value. Furthermore, we focused on BRCA and further investigated INSL6 from the perspective of the correlations with clinical characteristics, prognosis in different clinical subgroups, coexpression genes, and differentially expressed genes (DEGs) and PPI analysis. Overall survival and disease-specific survival analysis of subgroups in BRCA demonstrated that lower INSL6 expression had a worse prognosis. Therefore, INSL6 aberrant expression is associated with the progression and immune cell infiltration of the tumor, especially in KIRP and BRCA. Therefore, INSL6 may serve as a potential prognostic biomarker and the crosstalk between MI and tumor progression.

Prognostic and diagnostic values of non-coding RNAs as biomarkers for breast cancer: An umbrella review and pan-cancer analysis.

Background: Breast cancer (BC) is the most common cancer in women. The incidence and morbidity of BC are expected to rise rapidly. The stage at which BC is diagnosed has a significant impact on clinical outcomes. When detected early, an overall 5-year survival rate of up to 90% is possible. Although numerous studies have been conducted to assess the prognostic and diagnostic values of non-coding RNAs (ncRNAs) in breast cancer, their overall potential remains unclear. In this field of study, there are various systematic reviews and meta-analysis studies that report volumes of data. In this study, we tried to collect all these systematic reviews and meta-analysis studies in order to re-analyze their data without any restriction to breast cancer or non-coding RNA type, to make it as comprehensive as possible. Methods: Three databases, namely, PubMed, Scopus, and Web of Science (WoS), were searched to find any relevant meta-analysis studies. After thoroughly searching, the screening of titles, abstracts, and full-text and the quality of all included studies were assessed using the AMSTAR tool. All the required data including hazard ratios (HRs), sensitivity (SENS), and specificity (SPEC) were extracted for further analysis, and all analyses were carried out using Stata. Results: In the prognostic part, our initial search of three databases produced 10,548 articles, of which 58 studies were included in the current study. We assessed the correlation of non-coding RNA (ncRNA) expression with different survival outcomes in breast cancer patients: overall survival (OS) (HR = 1.521), disease-free survival (DFS) (HR = 1.33), recurrence-free survival (RFS) (HR = 1.66), progression-free survival (PFS) (HR = 1.71), metastasis-free survival (MFS) (HR = 0.90), and disease-specific survival (DSS) (HR = 0.37). After eliminating low-quality studies, the results did not change significantly. In the diagnostic part, 22 articles and 30 datasets were retrieved from 8,453 articles. The quality of all studies was determined. The bivariate and random-effects models were used to assess the diagnostic value of ncRNAs. The overall area under the curve (AUC) of ncRNAs in differentiated patients is 0.88 (SENS: 80% and SPEC: 82%). There was no difference in the potential of single and combined ncRNAs in differentiated BC patients. However, the overall potential of microRNAs (miRNAs) is higher than that of long non-coding RNAs (lncRNAs). No evidence of publication bias was found in the current study. Nine miRNAs, four lncRNAs, and five gene targets showed significant OS and RFS between normal and cancer patients based on pan-cancer data analysis, demonstrating their potential prognostic value. Conclusion: The present umbrella review showed that ncRNAs, including lncRNAs and miRNAs, can be used as prognostic and diagnostic biomarkers for breast cancer patients, regardless of the sample sources, ethnicity of patients, and subtype of breast cancer.

Identification of lysyl oxidase as an adipocyte-secreted mediator that promotes a partial mesenchymal-to-epithelial transition in MDA-MB-231 cells.

Breast cancer (BC) is the most common cancer in women worldwide, where adiposity has been linked to BC morbidity. In general, obese premenopausal women diagnosed with triple-negative BC (TNBC) tend to have larger tumours with more metastases, particularly to the bone marrow, and worse prognosis. Previous work using a 3-dimensional (3D) co-culture system consisting of TNBC cells, adipocytes and the laminin-rich extracellular matrix (ECM) trademarked as Matrigel, demonstrated that adipocytes and adipocyte-derived conditioned media (CM) caused a partial mesenchymal-to-epithelial transition (MET). Given that MET has been associated with secondary tumour formation, this study sought to identify molecular mediators responsible for this phenotypic change. Adipocytes were cultured with and without Matrigel, where semi-quantitative proteomics was used to identify proteins whose presence in the CM was induced or enhanced by Matrigel, which were referred to as adipocyte-secreted ECM-induced proteins (AEPs). The AEPs identified were assessed for association with prognosis in published proteomic datasets and prior literature. Of these, 4 were evaluated by the reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), followed by a functional and MET marker analysis of 1 AEP on MDA-MB-231 cells grown on Matrigel or as monolayers. The 4 AEPs showed a positive correlation between protein expression and poor prognosis. RT-qPCR analysis reported no significant change in AEPs mRNA expression. However, lysyl oxidase (LOX) was increased in CM of ECM-exposed adipocytes. Recombinant LOX (rLOX) caused the mesenchymal MDA-MB-231 TNBC cells to form less branched 3D structures and reduced the expression of vimentin. The data suggest that adipocyte-secreted LOX changes the mesenchymal phenotype of BC cells in a manner that could promote secondary tumour formation, particularly at sites high in adipocytes such as the bone marrow. Future efforts should focus on determining whether targeting LOX could reduce BC metastasis in obese individuals.

Impact of BMI on breast screening participation: a data linkage study

Abstract Background Regular mammographic screening can reduce breast cancer morbidity and mortality. Participation rates are suboptimal in Australia’s fully funded biennial breastscreening program (BreastScreen) for women aged 50-74. Despite obesity being a well-established risk factor for post-menopausal breast cancer, cross sectional data suggests obesity may be a risk factor for non-participation in recommended screening, due to adverse screening experiences. This research aimed to ascertain the link obesity and non-participation by using data linkage of routinely collected data. Methods Data for women age eligible for breast screening were linked between the NSW Cancer Registry and the Australian Longitudinal Study of Women’s Health (ALSWH) to create a cohort of women who either participated in screening as recommended or not. Women from the 1946-1951 ALSWH birth cohort were included in the study. These women reported BMI via 8 survey waves. The primary outcome was adherence to breast screening measured by frequency of screening over the follow-up period (1998-2016). Unadjusted risk ratios were calculated using mixed-effects logistic regression for the association between BMI and screening participation. Results The study included 2804 linked records of age eligible women (mean age of 52.37[SD 5.47]). 22.8% of the cohort were obese (BMI&amp;gt;30kg/m2). Obesity was significantly associated with non-recommended screening participation (screening within 3 years of last breast screen); odds ratio 1.63 (95% confidence interval 1.32 to 2.00, p &amp;lt; 0.0001). Conclusions Obesity has a significantly impact on recommended participation in a nationally provided breast screening program, despite obesity being a risk factor for post- menopausal breast cancer. Optimising participation among higher risk and under-screened women in under utilised breast cancer screening programs is warranted. Development of targeted interventions to increase screening participation among these higher risk women is needed. Key messages • Women living with obesity and less likely to participate in recommended breast screening. • Targeted interventions are needed to optimise participation in breast screening to ensure these higher risk women are not at higher risk of adverse outcomes due to breast cancer.

A quantitative characterization of the spatial distribution of brain metastases from breast cancer and respective molecular subtypes.

Brain metastases (BM) remain a significant cause of morbidity and mortality in breast cancer (BC) patients. Specific factors promoting the process of BM and predilection for selected neuro-anatomical regions remain unknown, yet may have major implications for prevention or treatment. Anatomical spatial distributions of BM from BC suggest a predominance of metastases in the hindbrain and cerebellum. Systematic approaches to quantifying BM location or location-based analyses based on molecular subtypes, however, remain largely unavailable. We analyzed stereotactic Cartesian coordinates derived from 134 patients undergoing gamma- knife radiosurgery (GKRS) for treatment of 407 breast cancer BMs to quantitatively study BM spatial distribution along principal component axes and by intrinsic molecular subtype (ER, PR, Herceptin). We used kernel density estimators (KDE) to highlight clustering and distribution regions in the brain, and we used the metric of mutual information (MI) to tease out subtle differences in the BM distributions associated with different molecular subtypes of BC. BM location maps according to vascular and anatomical distributions using Cartesian coordinates to aid in systematic classification of tumor locations were additionally developed. We corroborated that BC BMs show a consistent propensity to arise posteriorly and caudally, and that Her2+ tumors are relatively more likely to arise medially rather than laterally. To compare the distributions among varying BC molecular subtypes, the mutual information metric reveal that the ER-PR-Her2+ and ER-PR-Her2- subtypes show the smallest amount of mutual information and are most molecularly distinct. The kernel density contour plots show a propensity for triple negative BC to arise in more superiorly or cranially situated BMs. We present a novel and shareable workflow for characterizing and comparing spatial distributions of BM which may aid in identifying therapeutic or diagnostic targets and interactions with the tumor microenvironment. Further characterization of these patterns with larger multi-institutional data-sets may have major impacts on treatment or management of cancer patients.

Impact of Axillary Lymph Node Dissection and Sentinel Lymph Node Biopsy on Upper Limb Morbidity in Breast Cancer Patients: A Systematic Review and Meta-Analysis.

To evaluate the impact of axillary lymph node dissection (ALND) and sentinel lymph node biopsy (SLNB) on upper limb (UL) morbidity in breast cancer patients. Axillary de-escalation is motivated by a desire to reduce harm of ALND. Understanding the impact of axillary surgery and disparities in operative procedures on postoperative arm morbidity would better direct resources to the point of need and cement the need for de-escalation strategies. Embase, MEDLINE, CINAHL, and PsychINFO were searched from 1990 until March 2020. Included studies were randomized-controlled and observational studies focusing on UL morbidities, in breast surgery patients. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The prevalence of UL morbidity comparing SLNB and ALND at <12 months, 12 to 24 months, and beyond 24 months were analyzed. Sixty-seven studies were included. All studies reported a higher rate of lymphedema and pain after ALND compared with SLNB. The difference in lymphedema and pain prevalence between SLNB and ALND was 13.7% (95% confidence interval: 10.5-16.8, P <0.005) and 24.2% (95% confidence interval: 12.1-36.3, P <0.005), respectively. Pooled estimates for prevalence of reduced strength and range of motion after SLNB and ALND were 15.2% versus 30.9% and 17.1% versus 29.8%, respectively. Type of axillary surgery, greater body mass index, and radiotherapy were some of the predictors for UL morbidities. Prevalence of lymphedema after ALND was higher than previously estimated. ALND patients experienced greater rates of lymphedema, pain, reduced strength, and range of motion compared with SLNB. The findings support the continued drive to de-escalate axillary surgery.

Long-term Mammography Utilization after an Initial Randomized Intervention Period by all Underserved Chilean Women in the Clinics.

Simple SummaryChile has one of the highest rates of breast cancer in Latin America. In Chile, underserved women have lower rates of mammography screening than their medium-to-high-level counterparts and higher morbidity and mortality rates of breast cancer. After a successful randomized controlled trial of low-socioeconomic-status women in a primary care clinic, we used the RE-AIM (Reach, Effectiveness, Adoption, Maintenance) framework to establish the long-term effects of that intervention. After ten years, women at the low-SES intervention clinic continued to show higher mammography rates compared to women at middle-SES clinics; further, these results continued to be above the national rates for low-socioeconomic-status peers. The RE-AIM framework indicates some of the factors that may have contributed to this successful long-term effect among marginalized women in Chile.Chile has one of the highest rates of breast cancer in Latin America. Mammography rates among women, especially those of low socioeconomic status (SES), are thought to contribute to high breast cancer morbidity and mortality. A successful randomized controlled trial among women aged 50 to 70 in a low-SES primary care clinic in Chile led to a significant increase in mammography screening rates in a two-year intervention trial. This study assesses the sustainability of the intervention after ten years and identifies factors that might have been associated with a long-term effect using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework. The mammography rates among women aged 50 to 70 in the low-SES intervention clinic were compared to two populations of women aged 50 to 70 from middle-SES clinics and to national data. Qualitative data were used to answer questions of adoption, implementation, and maintenance, while quantitative data assessed the reach and effectiveness. After ten years, low-SES women at the intervention clinic maintained significantly higher mammography screening rates vs. middle-SES women at the comparison clinics (36.2% vs. 30.1% and 19.4% p < 0.0001). Women of a low SES at the intervention clinic also had significantly higher screening rates compared to women of a low SES at a national level (44.2% vs. 34.2% p < 0.0001). RE-AIM factors contributed to understanding the long-term difference in rates. Mailed contact, outreach interventions, and the integration of health promoters as part of the Community Advisory Board were important factors associated with the effects observed. This study provides information on factors that could contribute to reducing the social gap on breast cancer screening.

Prediction of Sentinel Lymph Node Biopsy Status in Breast Cancers with PET/CT Negative Axilla.

Background and Aim Prior knowledge of axillary node status can spare a lot of patients with early breast cancer morbidity due to an unnecessary axillary dissection. Our study compared various metabolic and pathological features that can predict the sentinel lymph node biopsy (SLNB) status in patients with positron emission tomography/computed tomography (PET/CT) negative axilla. Patients and Methods All consecutive patients with early breast cancers (< 5 cm) with PET/CT negative axilla who underwent breast surgery and SLNB from November 2016 to February 2020 were included. Various primary tumor (PT) pathological variables and metabolic variables on PET/CT such as maximum standardized uptake value (PT-SUV max ), metabolic tumor volume (PT-MTV), and total lesion glycolysis (PT-TLG) were compared using univariate and multivariate analyses for prediction of SLNB status. Results Overall 70 patients, all female, with mean age 55.6 years (range: 33–77) and mean tumor size 2.2 cm (range: 0.7–4.5), were included. SLNB was positive in 20% of patients ( n = 14) with nonsentinel nodes positive in 4% ( n = 3) patients. Comparing SLNB positive and negative groups, univariate analysis showed significant association of SLNB with low tumor grade, positive lymphovascular invasion (LVI), positive estrogen receptor (ER) status with lower mean K i -67 index (34.41 vs. 52.02%; p = 0.02), PT-SUV max (5.40 vs. 8.68; p = 0.036), PT-MTV (4.71 cc vs. 7.46 cc; p = 0.05), and PT-TLG (15.12 g/mL.cc vs. 37.10 g/mL.cc; p = 0.006). On multivariate analysis, only LVI status was a significant independent predictor of SLNB status (odds ratio = 6.23; 95% confidence interval: 1.15–33.6; p = 0.033). Conclusion SLNB is positive in approximately 20% of early breast cancers with PET/CT negative axilla and SLNB status appears to be independent of PT size. SLNB+ PTs were more likely to be LVI+ and ER + ve, with lower grade/K i -67/metabolic activity (SUV max /MTV/TLG) compared with SLNB–ve tumors. Logistic regression analysis revealed LVI status as the only significant independent predictor of sentinel lymph node status.

The Accuracy of Electrical Impedance Tomography for Breast Cancer Detection: A Systematic Review and Meta-Analysis.

Introduction Incidence of breast cancer (BC) in 2020 is about 2.26 million new cases. It is the first common cancer accounting for 11.7% of all cancer worldwide. Disease complications and the mortality rate of breast cancer are highly dependent on the early diagnosis. Therefore, novel human breast-imaging techniques play an important role in minimizing the breast cancer morbidity and mortality rate. Electrical impedance tomography (EIT) is a noninvasive technique to image the breast using the electrical impedance behavior of the body tissues. Objectives The aims of this manuscript are as follows: (1) a comprehensive investigation of the accuracy of EIT for breast cancer diagnosis through searching pieces of evidence in the valid databases and (2) meta-analyses of the results. Methods The systematic search was performed in the electronic databases including PubMed, Web of Science, EMBASE, Science Direct, ProQuest, Scopus, and Google Scholar without time and language limitation until January 2021. Search terms were “EIT” and “Breast Cancer” with their synonyms. Relevant studies were included based on PRISMA and study objectives. Quality of studies and risk of bias were performed by QUADAS-2 tools. Then, relevant data were extracted in Excel form. The hierarchical/bivariate meta-analysis was performed with “metandi” package for the ROC plot of sensitivity and specificity. Forest plot of the Accuracy index and double arcsine transformations was applied to stabilize the variance. The heterogeneity of the studies was evaluated by the forest plots, χ2 test (assuming a significance at the a-level of 10%), and the I2 statistic for the Accuracy index. Results A total of 4027 articles were found. Finally, 12 of which met our criteria. Overall, these articles included studies of 5487 breast cancer patients. EIT had an overall pooled sensitivity and specificity of 75.88% (95% CI, 61.92% to 85.89%) and 82.04% (95% CI, 69.72% to 90.06%), respectively. The pooled diagnostic odds ratio was 14.37 (95% CI, 6.22% to 33.20%), and the pooled effect of accuracy was 0.79 with 95% CI (0.73, 0.83). Conclusions This study showed that EIT can be used as a useful method alongside mammography. EIT sensitivity could not be compared with the sensitivity of MRI, but in terms of specificity, it can be considered as a new method that probably can get more attention. Furthermore, large-scale studies will be needed to support the evidence.

Characterizing Geospatial Access and Potential Barriers for Women Presenting With Breast Concerns to Bugando Medical Center in Mwanza, Tanzania

PURPOSE In Tanzania, high breast cancer morbidity and mortality can be attributed in part to delays due to poor access to comprehensive cancer services. Bugando Medical Center (BMC) is one of four tertiary care hospitals in Tanzania. We aimed to describe the catchment area and potential barriers to access for women presenting to BMC with breast concerns. METHODS This prospective cohort included women presenting to BMC between September 2019 and January 2021. Patients were geocoded to residential regions and a presentation rate (PR) for each region was calculated using the number of presenting patients per at-risk female population. The main travel route from each region's referral hospital to BMC was determined using Google maps. We used descriptive statistics to depict geospatial, demographic, and clinical variables. RESULTS The catchment area included 10.5 million women from eight regions in the Lake Zone of Tanzania. We studied 547 patients aged 18-87 (mean: 44.3), 35% (n = 196) had health insurance, and mean PR was 5.26 per 100,000 women (range: 2.01-13.86). Median distance to BMC was 121 km (IQR: 3-247) and 18% of patients likely required a ferry. As distance increased, PR tended to decrease. PRs were lower for three regions where a ferry was indicated for travel (2.01, 2.32 and 3.06). There were 151 (28%) patients diagnosed with breast cancer, with a mean breast cancer PR of 1.45 per 100,000 women (range: 0.64-3.12). The proportion of breast cancers diagnosed increased with increasing travel distance. Additionally, 51 (26%) breast cancer patients were lost to follow up without any treatment. CONCLUSION BMC has a large geographic catchment area comprised of eight regions, all with low breast cancer PR. Our findings indicate that burdensome geographic access to cancer care, lack of health insurance, and lost to follow-up, are likely contributing to the high breast cancer mortality in Tanzania.