Breast Cancer Research Articles

Territorial health inequalities in breast cancer mortality across France from 1968 to 2017

Abstract Background Territorial health inequalities are of growing concern in countries with universal health systems. From 2003, three successive national cancer plans were launched in France, aiming to improve prevention and treatment. Regions in France are responsible for strategic and financial management of healthcare within their boundaries, which, until 2016, included up to 8 departments. In this study, we analyze the evolution of between and within-region territorial inequalities in breast cancer mortality over 50 years. Methods We used direct and indirect standardization to analyze trends in breast cancer mortality for women aged 25 to 74 years between 1968 and 2017 in each department of metropolitan France. We analyzed the evolution of relative inequalities over time using standard errors of age-adjusted rates. We used multilevel Poisson regression to estimate how much the regional level contributed to territorial variation. Results Over the period 1968 to 1992, breast cancer standardized mortality ratios (SMRs) increased (+16%) while relative territorial inequalities decreased (-21%). After 1997, SMRs decreased (-23%) but territorial inequalities remained unchanged. In 18 out of 22 regions, inequalities were lower at the end than at the start of the study period. Period proved to be the most important determinant of variation in mortality. However, multilevel models also suggested that the regional level explained most of the remaining variation in each period (from 50% to over 80%). Conclusions Over the study period in most French regions, breast cancer mortality has decreased, and so have relative inequalities. Nevertheless, there is evidence that regions have performed differently. The proportion of variation explained by the regional level suggests the continued relevance of the health system on breast cancer mortality. Key messages • Territorial inequality in breast cancer mortality has decreased in France over the 1968-2017 period. • In most regions, disparities between departments have decreased.

Albumin-To-Alkaline Phosphatase Ratio as a New Early Predictive Marker of Axillary Response in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy: A Pilot Study

Background and Objectives: The Albumin-to-Alkaline Phosphatase ratio (AAPR) is an easily applicable and cost-effective marker investigated as an outcome predictor in solid cancers. Preliminary evidence in breast cancer suggests that a low AAPR correlates with a poor response to neoadjuvant chemotherapy (NAC) in primary tumors. However, data regarding the axillary response are lacking. This study aims to evaluate whether the AAPR can predict the axillary response in initially nodal-positive (cN+) breast cancer patients undergoing NAC. Materials and Methods: Clinical and biochemical variables of cN+ breast cancer patients undergoing NAC were collected. Pre-NAC albumin and alkaline phosphatase serum values were utilized in the AAPR calculation. Fisher’s exact test was performed to identify differences between the two groups of patients (high and low AAPR according to the cut-off reported in the literature). The primary outcome was the nodal pathologic complete response (pCR) rate in the two groups of patients. Results: Nodal pCR was achieved in 20/45 (44.4%) patients. A total of 36/45 (80%) patients had an AAPR > 0.583. Among patient and tumor characteristics, the only statistically significant difference between the two groups was the axillary pCR between the low and high AAPR groups (p-value = 0.03, OR = 0.129, 95% CI = 0.00–0.835). Conclusions: This pilot study suggests that the pre-treatment AAPR might be an early predictor of axillary response in cN+ breast cancer patients undergoing NAC. This result justifies further investigation in larger prospective trials to validate this finding.

Current advancements in PD-L1 modulation by CMTM6 in malignant tumors

Abstract The CKLF-like MARVEL transmembrane domain-containing protein 6 (CMTM6), a member of the chemokine-like factor superfamily, binds to programmed death-ligand 1 (PD-L1) on the cell membrane, thereby impeding PD-L1’s lysosomal degradation and sustaining its expression. In recent years, extensive studies on PD-L1 have provided insights into its function as an immunepoint inhibitor involved in tumor cell immune evasion. The specific interaction between CMTM6 and PD-L1 suggests a potential role in tumor cell immune evasion and suppression, potentially offering a novel therapeutic target for cancer immunotherapy. Currently, the research on CMTM6 and PD-L1 in diverse tumors and diseases is limited, but their significant roles are indicated. This article provides an overview of the impact of CMTM6 on the immune microenvironment in different types of cancer (such as lung cancer, breast cancer, and liver cancer), and summarizes the effects of CMTM6 on the occurrence and development of various tumors.

Regional variations in breast cancer screening uptake and its associated factors in Ghana

Abstract Introduction Timely identification of breast cancer is critical for successful treatment and prevention, reducing its burden. Despite its significance, breast cancer screening services in Ghana are underutilized, with considerable regional variations in uptake rates. We examined the regional differences in breast cancer screening uptake and its associated factors in Ghana. Methods We analyzed data from 15,014 women of reproductive age from the 2022 Ghana Demographic and Health Survey. Spatial mapping illustrated regional variations in screening uptake. Multilevel logistic regression was employed to examine the factors associated with breast cancer screening uptake. Results National breast cancer screening prevalence was 18.4%, with regional variations observed across the 16 regions. Eastern, Western, Brong Ahafo, and Greater Accra had the highest screening uptake. The likelihood of breast cancer screening was higher among women aged 45-49 (aOR = 3.59; 95% CI = 12.52, 5.12), Married women (aOR = 1.44; 95% CI = 1.17-1.77), Higher education, employment, health insurance, recent health facility visits, media access, and wealth index (middle: aOR = 1.45, 95% CI = 1.08, 1.94; richest: aOR = 1.91, 95% CI = 1.36, 2.70). Islamic and African Traditional affiliations decrease screening likelihood (aOR = 0.77; 95% CI = 0.63, 0.95; aOR = 0.46; 95% CI = 0.22, 0.97). Rural residence and specific regions (Ashanti, Oti, Savannah, Upper West) reduce odds, while living in North East increases odds (aOR: 1.86; 95% CI = 1.14-3.03). Conclusions Cost-effective breast cancer screening services are crucial, particularly in rural areas with geographical disparities. Culturally and religiously sensitive protocols are needed to address regional and religious differences. Expanding Ghana’s national health insurance to cover preventive measures like breast cancer screening is essential. Promoting awareness through conventional and digital platforms is crucial for advocating screening. Key messages • Addressing geographical and cultural differences crucial for equitable breast cancer screening in Ghana. • Expanding health insurance and raising awareness vital to promote screening access and reduce disparities.

The association between heart failure diagnosis and the incidence of cancer: a longitudinal analysis of the United Kingdom Biobank

Abstract Background Heart failure (HF) and cancer represent prevalent chronic conditions with a high burden of disease worldwide. Several studies have shown a high frequency of coexistence of these two entities, highlighting a potential bidirectional association. However, few longitudinal studies have explored whether patients with HF have a significantly increased risk of cancer and if comorbidity profiles affect this risk. Purpose To explore the association between incident HF diagnosis and cancer development in UK Biobank participants after adjustment by potential confounders. Methods We conducted a retrospective cohort study in UK Biobank. HF and cancer diagnoses were determined using diagnoses and patient reports. We evaluated breast, liver, lung, prostate, colorectal, uterus, and hematological cancer. Individuals with a history of HF or cancer diagnosed before the baseline assessment were excluded. The primary exposure was incident HF diagnosis after enrollment, and the primary outcome was incident cancer during follow-up. Multivariate Cox proportional hazard regression models using time-varying covariates were used to calculate hazard ratios (HR) for the explored associations with overall cancer and by major cancer type. A Bonferroni-corrected p-value < 0.003 was considered statistically significant to control for family-wise error rate. Results 476,652 patients were analyzed (mean age: 56.3 years; 57.8% females). Over a median follow-up of 13.7 years, 12,461 (2.6%) developed HF, and 34,452 (7.2%) were diagnosed with cancer. Incident HF was significantly associated with increased overall cancer risk (HR 1.34, 95% CI 1.22–1.48. p<0.001), as well as lung (HR 1.30, 95% CI 1.18–1.43), and hematological cancers (HR 1.54, 95% CI 1.25–1.91. p<0.001) (Figure). Conclusion Despite sharing multiple comorbidities and risk factors, incident HF remained significantly associated with a higher cancer risk even after multivariable adjustment by relevant confounders. Nevertheless, confounding bias and especially detection bias, cannot be ruled out in the present analysis. Further research is necessary to validate these findings and elucidate the mechanisms underlying this association.Figure

An analysis of the virtual cardio-oncology research initiative (VICORI) resource: bleeding risk among cancer patients beyond 1-year post-myocardial infarction

Abstract Introduction Cardiovascular disease (CVD) and cancer are common causes of morbidity and mortality. Advancements in treatment strategies for both diseases have resulted in a growing population who live with both conditions. Myocardial infarction (MI) represents approximately 20% of all CVD admissions in cancer patients and 10% of patients who present with an acute MI have cancer. Managing MI patients with cancer require careful balancing of their ischaemic and bleeding risks. While dual antiplatelet therapy (DAPT) increases a patient’s bleeding risk, cancer patients are at further increased risk due to a range of direct and indirect cancer effects. While our recent studies demonstrated an increased bleeding risk in cancer patients in the 1st year after MI (the period of intensive APT), it is currently not known if this risk is sustained beyond this period. VICORI is the world’s first whole-country cardio-oncology research platform, linking data from the National Cancer Registration and Analysis Service, National Institute for Cardiovascular Outcomes Research and Hospital Episode Statistics [1]. We investigated the risk of bleeding among MI patients in the 2nd year post-MI, where a large majority of patients would have completed a course of DAPT, stratified by the presence or absence of cancer. Methods In this retrospective observational study, we investigated the risk of bleeding following an MI between 2006-2019, in patients with and without cancer. Cancer was defined as a diagnosis of cancer in the 1-year preceding MI. Patients who lived past the 1st year after MI were followed-up from 12 to 24 months after their MI. We used inverse probability weighting based on propensity scores to produce a balanced cohort of patients with and without cancer. Cox proportional hazard and flexible parametric modelling were used to investigate cancer as a predictor of bleeding. Subgroup analyses were performed on stent status, MI and cancer type. Results Of 506280 patients presenting with MI, 5666 (1.1%) had cancer while 500614 (98.9%) did not. Prostate (n=1377), colorectal (n=1024), lung (n=490), breast (n=448) and bladder (n=334) cancers were among the most common types of cancers. The rate (hazard) of bleeding in MI was higher in patients with cancer in the 2nd year post-MI (HR:1.42, 95%CI 1.29-1.56) compared to those without. From the flexible parametric survival analysis, the risk of bleeding in cancer patients in the 2nd year post-MI was lower compared to the 1st year but remained statistically significant compared to non-cancer patients. Conclusion In this large real-world study, cancer patients have a persistent, increased bleeding risk beyond the 1-year post-MI period, compared to those without cancer, and this risk differed by type of cancer. Further work is needed to identify specific patient characteristics in each patient sub-group which alters one’s ischaemic or bleeding risk so they can be balanced favourably with personalised strategies.

Factors associated with physical activity in individuals with metastatic cancer: a UK cross-sectional survey.

Physical activity is safe and feasible for individuals with metastatic cancer and may support symptom management. We investigated the extent to which individuals with metastatic cancer are meeting the World Health Organisation (WHO) moderate-vigorous physical activity (MVPA) guideline, factors associated with meeting the guideline, and perceptions about physical activity and receiving physical activity advice. Data were from UK adults with metastatic breast, prostate, or colorectal cancer who completed the Healthy Lifestyle After Cancer survey (N = 588). Self-reported clinical, demographic, and physical activity (Godin Leisure-Time Exercise Questionnaire) data were collected. Logistic regression models assessed whether clinical and demographic factors were associated with meeting the MVPA guideline. Most (59%) individuals with metastatic cancer were not meeting the WHO guideline of 150min of MVPA per week. Adjusting for cancer type, the odds of meeting the MVPA guideline were lower for unemployed individuals (OR = 0.47, 95% CI = 0.23-0.77) and ethnic minorities (OR = 0.44, 95% CI = 0.22-0.89), but higher for those with a university education (OR = 1.89, 95% CI = 1.0-3.57). Most (63.5%) participants felt they should be doing more physical activity. However, 70.1% did not receive any physical activity advice or support, despite 73.6% wanting to receive it. People with metastatic cancer may need further support to address inadequate levels of physical activity. The differences observed between demographic sub-groups suggest this may be more beneficial for those less likely to engage in physical activity. Individuals with metastatic cancer are likely to benefit from increased physical activity support, which considers the needs of diverse demographic groups.

A systematic review of cancer overdiagnosis in multimorbid patients

Abstract Background Cancer screening looks for early signs of cancer in people who do not currently exhibit symptoms. However, screening can also identify abnormalities that do not progress to produce symptoms or death. This could include the identification of tumours, which stop growing or grow very slowly; patients usually die with them rather than from them. We systematically reviewed the literature to investigate the harmful consequences of cancer overdiagnosis in multi-morbid patients. Methods We followed the PRISMA reporting guidelines and registered the review with PROSPERO (CRD42024475175). A Population, Intervention, Comparator, Outcome and Study design (PICOS) framework was used as an organising framework. Peer-reviewed studies were included except case series, case report reviews and conference abstracts. Four large databases (Medline, Embase, APA Psych INFO and Scopus) were searched in Nov23 using appropriate keywords grouped into categories: multimorbidity, overdiagnosis, patient harms, cancer screening. Titles were screened according to the eligibility criteria and their quality assessed. Studies needed to have investigated the extent of harm caused by overdiagnosis (e.g., overtreatment). Results A total of 200 articles were retrieved, with seven meeting our inclusion criteria. All included studies were based in the US. Breast and prostate cancer overdiagnosis was reported to be 15% higher in multimorbid populations compared to the average-risk population. Multimorbid individuals were more vulnerable to the harms of cancer overdiagnosis, with psychological, physical and financial harms reported. Conclusions These findings contribute valuable insights into the intricate interplay between comorbidities, cancer overdiagnosis, and associated harms. Radical treatment interventions in multi-morbid patients can carry greater risk of complications. Current screening guidelines only address average-risk populations; future guidelines need to reflect these findings. Key messages • Cancer overdiagnosis was found to be higher in multimorbid populations compared to the average-risk population. • Multimorbid individuals are also more vulnerable to the harms of cancer overdiagnosis.

Artificial Intelligence in Medical Diagnostics

Artificial intelligence (AI) is an essential tool in the medical sector that contributes significantly to medical imaging, medical pathology, histology, genomic study, predictive analysis, etc. It is being increasingly used not only in breast and lung cancer diagnosis and screening, and genetic disease identification but also in personalized decision-making during the treatment of these diseases. The quality and availability of unbiased data is a key challenge. Algorithmic bias and interpretability are significant concerns as well. Improving the use of AI in medical diagnostics could be achieved through continuous monitoring, access to highly accurate datasets, and timely intervention by healthcare professionals. J Bangladesh Coll Phys Surg 2024; 42: 379-382

Virtual patient analysis identifies strategies to improve the performance of predictive biomarkers for PD-1 blockade

Patients with metastatic triple-negative breast cancer (TNBC) show variable responses to PD-1 inhibition. Efficient patient selection by predictive biomarkers would be desirable but is hindered by the limited performance of existing biomarkers. Here, we leveraged in silico patient cohorts generated using a quantitative systems pharmacology model of metastatic TNBC, informed by transcriptomic and clinical data, to explore potential ways to improve patient selection. We evaluated and quantified the performance of 90 biomarker candidates, including various cellular and molecular species, at different cutoffs by a cutoff-based biomarker testing algorithm combined with machine learning-based feature selection. Combinations of pretreatment biomarkers improved the specificity compared to single biomarkers at the cost of reduced sensitivity. On the other hand, early on-treatment biomarkers, such as the relative change in tumor diameter from baseline measured at two weeks after treatment initiation, achieved remarkably higher sensitivity and specificity. Further, blood-based biomarkers had a comparable ability to tumor- or lymph node-based biomarkers in identifying a subset of responders, potentially suggesting a less invasive way for patient selection.

Exploration of research projects on personalised prevention supported by the European Commission

Abstract The interaction between environmental exposures, lifestyle factors, and genetic predisposition affect individual susceptibility to chronic diseases. Personalised Prevention (PP) has emerged in the recent years as potential approach to integrate traditional public health approaches in prevention. The implementation of PP into national health systems so far has not realized its full potential due to a number of obstacles including scanty evidence from research. Within the project “PROPHET: A Map for Personalised Prevention in the Future of Healthcare”, we conducted an extensive mapping of currently active research projects in the field of PP. We carried out a scoping review according to Arksey and O’Malley methodology, followed by consultations with experts in personalised medicine and prevention. We included 45 ongoing research projects on PP, of which 57.8% were funded by Horizon Europe, 35.5% by Horizon 2020, and 6.7% by Eu4Health. Regarding disease types, 40% of the projects were about cancer, 20% on cardiovascular and 20% on neurological and psychiatric diseases, followed by metabolic diseases and other chronic conditions. Overall, the EC allocated approximately €160 million to cancer personalised prevention projects, roughly double of the funding dedicated to cardiovascular, neurological and psychiatric diseases. The emphasis on cancer projects is noteworthy, with Horizon Europe emerging as the main funding programme aligned with the ongoing Cancer Mission. Regardless of the disease, most of the projects addressed primary and secondary personalised prevention research. This is in line with the limited approaches in PP in the setting of primary and secondary personalised prevention (e.g., genetic testing to identify high risk subjects for breast cancer) compared to tertiary prevention (e.g., pharmacogenomics). This comprehensive mapping underlines the EU’s continued commitment to promoting PP, which is fundamental to the future of healthcare. Key messages • The EC prioritises significant financial resources towards cancer personalised prevention research projects, highlighting Cancer Mission as a focal initiative in the personalised prevention field. • European-funded projects focus on primary and secondary personalised prevention strategies. This suggest that we currently miss evidence in these areas.

Childhood-to-adulthood body size trajectory and cancer risk: a prospective cohort study

Abstract Background While excess weight in adulthood and childhood has been associated with increased cancer risk, the link between childhood-to-adulthood body size trajectories and cancer risk requires further investigation. Methods We used data from the UK Biobank, a prospective population-based cohort study. The main exposure was childhood-to-adulthood body size trajectory, constructed from self-reported body at age 10 (categories: thinner, average, and plumper than average) and measured body mass index (BMI) at recruitment (normal weight, overweight, and obese). Primary outcome was obesity-related cancer (13 different cancer types). Results During a median follow-up of 11.7 years, 21,289 participants developed obesity-related cancers. Having a larger body size at age 10 was strongly associated with being overweight or obese in adulthood. Compared to participants with average childhood to normal adulthood body size trajectory, all trajectories ending in overweight or obesity in adulthood were strongly associated with an increased risk of obesity-related cancers. The strength of the association was mostly determined by adulthood BMI, and similar patterns were observed for colorectal, endometrial, kidney, pancreatic and esophageal cancer. However, a larger body size in childhood was associated with a lower risk of postmenopausal breast cancer. Conclusions Although a larger body size in childhood predisposes to overweight and obesity in adulthood, it does not necessarily predispose to an increased obesity-related cancer risk if measures to maintain a healthy weight are taken in adulthood. Key messages • While larger body size in childhood predisposes individuals to overweight and obesity in adulthood, maintaining a healthy weight in adulthood may help mitigate the risk of obesity-related cancers. • Our findings highlight the importance of preventing and reducing overweight and obesity in adulthood for primary cancer prevention.

Does HFpEF represent a risk factor and a marker of cardiotoxicity in patients undergoing cancer treatment?

Abstract Background The prevalence of heart failure with preserved ejection fraction (HFpEF) increases with the aging of our population and shares risk factors with cancer. Furthermore, HFpEF conveys a worse prognosis if it remains unrecognized and untreated. However, it is not considered as a surrogate marker in the baseline risk stratificatoin of patients that will undergo potentially cardiotoxic cancer treatments. Moreover, the definition of cardiotoxicity focuses mainly on systolic dysfunction, based on left ventricular ejection fraction and global longitudinal strain changes. Data on the prevalence of new-onset HFpEF during cancer treatment are limited. Purpose We evaluated the prevalence of HFpEF in cancer patients followed in our cardio-oncology clinic, with new cancer therapy-related cardiovascular toxicity (CTR-CVT) events in patients with known HFpEF prior to cancer therapy. We also assessed the prevalence of patients diagnosed with HFpEF while undergoing cancer therapy. Methods A total of 630 cancer patients referred for either baseline evaluation, on-treatment surveillance, long-term follow-up or new complaints suspect for cardiovascular disease were included in this real-world observational study, with a mean follow-up duration of 507 days. They underwent comprehensive workup in accordance with the ESC guidelines, including clinical assessment, electrocardiogram, echocardiography and biomarker testing. Results From the total population, 36 (5.7%) were diagnosed with HFpEF prior to cancer treatment initiation. Among these, 18 (50%) developed CTR-CVT during follow-up, mainly heart failure events (cancer-therapy related cardiac dysfunction or HFpEF decompensation). Independent of baseline characteristics, 233 patients (37.0%) developed a heart failure event during or after cancer treatment. Of these, 92 patients (14.6% of the total population, 39.5% of all HF events on treatment) developed a HFpEF event during or after cancer treatment. Of these HFpEF events, 42 patients (45.7%) were known with pre-existing cardiovascular disease, of whom only 14 (15.2%) with pre-existing HFpEF. In 50 patients (54.3%) the HFpEF diagnosis was made de novo during (or after) cancer treatment. Patients developing HFpEF were mostly female (n=54, 58.7%) and relatively young (mean age 62.0 years). Most HFpEF events occurred in breast cancer patients (n=32, 34.7%), prostate cancer patients (n=13, 14.1%) and multiple myeloma patients (n=9, 9.8%). Conclusions HFpEF is frequently overlooked, but conveys a high risk of developing CTR-CVT and should therefore be taken into account in the baseline risk stratification. Furthermore, HFpEF is responsible for an important morbidity burden during or after cancer cardiotoxic treatments, even in patients without prior diagnosis of HFpEF at baseline evaluation. Further studies are needed to evaluate if this population may benefit from specific management and treatment strategies in order to improve prognosis.Prevalence of HFpEF in cancer patients

Impact of the Prepectoral Breast Reconstruction Assessment Score on Expander-Based Reconstruction Success

Background/Objectives: The rising incidence of breast cancer has led to more mastectomies and increased demand for reconstruction. While retropectoral reconstruction with expanders is common, it has complications like postoperative pain and animation deformity. Prepectoral reconstruction, aided by advancements in biological and synthetic meshes, offers a promising alternative. Methods: This study prospectively evaluated the “Prepectoral Breast Reconstruction Assessment Score” on 20 patients undergoing mastectomy at Policlinico Umberto I, Rome, from July 2022 to February 2024. Patients with scores between 5 and 8 were included. The procedure involved the use of ADM (Acellular Dermal Matrix) or titanium-coated polypropylene mesh, followed by postoperative expansions and final implant placement after six months. Results: The mean age of patients was 51.85 years, with a mean BMI of 24.145 kg/m2. ADM was used in 15 cases and synthetic mesh in 5. Complications were one exposure of the expander, one superficial skin necrosis and one seroma. Statistical analysis showed a trend toward fewer complications with higher scores, though this was not statistically significant (p-value = 0.139). Conclusions: Prepectoral reconstruction with expanders is a viable option, offering benefits such as reduced operating time, better volume control, and a more natural breast contour compared to the retropectoral approach. Although the trend suggests fewer complications with higher assessment scores, further studies with larger samples are needed for confirmation.

Novel deep learning algorithm demonstrates strong performance for detection and quantification of breast arterial calcification and associates with cardiovascular disease

Abstract Background Breast arterial calcification (BAC) on mammography is associated with cardiovascular disease (CVD).1, 2 Given mammography is widely used as part of national breast cancer screening programs, routine reporting of BAC could address current limitations of CVD detection in women. Fully automated artificial intelligence (AI) software can facilitate seamless integration of BAC assessment alongside standard radiological evaluation of mammograms. and advancement in AI imaging software may result in clinically significant, superior BAC detection. Purpose To evaluate the performance of a deep-learning, fully-automated BAC detection algorithm against gold standard human BAC detection, and to evaluate its association with cardiovascular risk and disease. Methods A cohort of 285 women (mean age 61) with 2D digital mammography and CVD assessment with either an anatomic or functional test were evaluated. Cardiovascular risk factors were obtained from medical records. Visual BAC (vBAC) was assessed as present/absent by independent reviewers and BAC was scaled by an algorithm incorporating size, length, density and location (aBAC, 0-100). Diagnostic performance of vBAC and aBAC were compared and expressed as area under the receiver operator characteristic curve (AUC). Cardiovascular risk factor and disease prevalence was compared between vBAC and aBAC with CVD status defined by either abnormal anatomical or functional testing. Results The prevalence of vBAC and aBAC were 30.5% and 59.6%, respectively. The algorithm showed excellent discrimination for BAC detection compared with vBAC (AUC 0.92 [95% CI 0.89-0.98]), with sensitivity 94% and negative predictive value 96%. Interpretation took on average 144 seconds/patient with vBAC and 10 seconds/patient with aBAC (p<0.001). We identified 88 discordant cases (vBAC negative, aBAC positive), which were all represented by ‘faint’ BAC scores (<25). aBAC detected a greater proportion of patients with traditional cardiac risk factors, particularly in women <65 years (Figure 1). CVD was present in 136 (48%), among whom 37.5% were detected by vBAC and 61.7% by aBAC. CVD was present in 42% of the 88 discordant cases. Increasing BAC score was associated with increased relative risk of CVD presence (Figure 2). Conclusion Algorithmic scoring of BAC demonstrates a high performance and is faster to perform when compared to vBAC. Furthermore, it identifies greater proportion of women with higher cardiovascular risk and those with prevalent CVD. Lastly, aBAC detects ‘faint’ (visually missed) lesions that may have significant clinical implications.

Transcriptional responses to direct and indirect TGFB1 stimulation in cancerous and noncancerous mammary epithelial cells

BackgroundTransforming growth factor beta (TGFβ) is important for the morphogenesis and secretory function of the mammary gland. It is one of the main activators of the epithelial–mesenchymal transition (EMT), a process important for tissue remodeling and regeneration. It also provides cells with the plasticity to form metastases during tumor progression. Noncancerous and cancer cells respond differently to TGFβ. However, knowledge of the cellular signaling cascades triggered by TGFβ in various cell types is still limited.MethodsMCF10A (noncancerous, originating from fibrotic breast tissue) and MCF7 (cancer, estrogen receptor-positive) breast epithelial cells were treated with TGFB1 directly or through conditioned media from stimulated cells. Transcriptional changes (via RNA-seq) were assessed in untreated cells and after 1–6 days of treatment. Differentially expressed genes were detected with DESeq2 and the hallmark collection was selected for gene set enrichment analysis.ResultsTGFB1 induces EMT in both the MCF10A and MCF7 cell lines but via slightly different mechanisms (signaling through SMAD3 is more active in MCF7 cells). Many EMT-related genes are expressed in MCF10A cells at baseline. Both cell lines respond to TGFB1 by decreasing the expression of genes involved in cell proliferation: through the repression of MYC (and the protein targets) in MCF10A cells and the activation of p63-dependent signaling in MCF7 cells (CDKN1A and CDKN2B, which are responsible for the inhibition of cyclin-dependent kinases, are upregulated). In addition, estrogen receptor signaling is inhibited and caspase-dependent cell death is induced only in MCF7 cells. Direct incubation with TGFB1 and treatment of cells with conditioned media similarly affected transcriptional profiles. However, TGFB1-induced protein secretion is more pronounced in MCF10A cells; therefore, the signaling is propagated through conditioned media (bystander effect) more effectively in MCF10A cells than in MCF7 cells.ConclusionsEstrogen receptor-positive breast cancer patients may benefit from high levels of TGFB1 expression due to the repression of estrogen receptor signaling, inhibition of proliferation, and induction of apoptosis in cancer cells. However, some TGFB1-stimulated cells may undergo EMT, which increases the risk of metastasis.

Echocardiographic variables may improve baseline risk prediction of cancer therapy related cardiac dysfunction

Abstract Background Baseline prediction of cancer therapy related cardiac dysfunction (CTRCD) in clinical practice is difficult, despite many known cancer and cardiovascular risk factors. Risk scores exist, including the HFA-ICOS score which is recommended by the 2022 European Society of Cardiology (ESC) Cardio-Oncology guidelines. Validation of such risk scores is required though, and identification of alternative risk factors that may improve risk prediction is needed. Purpose To assess the accuracy of the HFA-ICOS score for predicting CTRCD, and identify new risk factors with a focus on baseline echocardiography. Methods Echocardiograms and medical records were assessed for a cohort of breast cancer patients receiving trastuzumab or an anthracycline, who underwent serial echocardiographic monitoring. CTRCD was defined according to the 2022 ESC Cardio-Oncology guidelines. Baseline risk factors and echocardiography were compared between CTRCD and non-CTRCD groups, and the accuracy of the HFA-ICOS score in predicting CTRCD assessed. Results Data from 258 patients were analysed with CTRCD occurring in 23 (9%). 135 were low risk, 85 moderate-risk, 31 high-risk and 8 very high-risk according to the HFA-ICOS score with a trend of increasing rates of CTRCD with each risk category: 5%, 12%, 10%, 25%, respectively. The sensitivity and specificity of a combined moderate/high/very high-risk group was 70% and 54% (AUC 0.618, 95% CI 0.5-0.73). Only three individual baseline variables were associated with CTRCD in this cohort; ejection fraction 50-54%, (18% vs 2%, p=0.0027), borderline/abnormal average global longitudinal strain <-18, (43% vs 19%, p=0.04) and combination anthracycline plus trastuzumab, (45% vs 22%, p=0.0392). Left atrial volume index >34mL/m² was also higher in the CTRCD group (38% vs 23%) although not statistically significant. A simplified risk score using only these variables yielded a sensitivity and specificity of 74% and 53%, respectively (AUC 0.633, 95% CI 0.52-0.75). Conclusion Baseline prediction of CTRCD remains difficult in clinical practice. Although HFA-ICOS risk categories correlate with CTRCD diagnosis, the overall sensitivity is only moderate. Echocardiographic variables may further enhance risk prediction to enable development of targeted monitoring strategies.HFA-ICOS risk score categoriesROC curves

Breast arterial calcification: a potential novel imaging marker for HFpEF

Abstract Background Breast arterial calcification (BAC) on mammography has been shown to associate with cardiovascular disease, however the association with heart failure (HF) remains largely uncharacterised. BAC is a medial arterial calcification process, which is a marker of vascular stiffness, a key contributor to diastolic dysfunction (DD) and HFpEF. We sought to evaluate the association between BAC and HFpEF. Purpose This study aims to assess the relationship between BAC status and HFpEF. Methods This retrospective cross-sectional study included 100 consecutive patients with clinically indicated mammography and echocardiography within 6 months of each other. BAC was visually assessed to determine presence or absence. HFpEF was diagnosed based on combined clinical and echocardiographic assessment. DD was defined by Mitter et. al’s(1) criteria after review of echocardiograms. Logistic regression analysis with Odds Ratio (OR) and (95% confidence intervals) are reported for association with any HF, HFpEF, or DD adjusting for modifiable (body mass index, hypertension, hyperlipidaemia, current smoking, diabetes mellitus) and non-modifiable (age, past smoking breast cancer, past ischaemic heart disease (IHD), atrial fibrillation (AF), chronic kidney disease (CKD)) risk factors. Results The prevalence of BAC was 27% and 13% had HFpEF and 55.8% had DD. Patients with BAC were older (mean age 73±13 vs 57±13, p<0.01) with greater proportion of hypertension (66.67% vs 39.73%, p=0.02), hypercholesterolaemia (70.37% vs 43.84%, p=0.02), AF (p<0.01), previous IHD (p=0.01), and CKD (p<0.01). After adjustment for these variables, BAC was independently associated with HFpEF diagnosis for modifiable risk factors: (OR 2.47 [0.50-12.10], p<0.27) and non-modifiable factors (OR 6.96 [1.72-33.31], p<0.01). BAC was also independently associated with echo defined DD: adjusted for modifiable risk factors (OR 8.67 [2.49-42.16], p<0.01), and non-modifiable risk factors (OR 8.25 [2.44-38.27], p<0.01). Conclusions BAC is associated with HF presence, particularly HFpEF and DD. Further research is required to elucidate the role of shared pathophysiological mechanisms, such as vascular stiffness and general arterial calcification, common to BAC, DD, and HFpEF. In the future, BAC may act as a useful surrogate and opportunistic marker to instigate further review if implemented in established widespread breast-screening programs for detection of subclinical disease.Figure 1:Case example of imaging assess

The effects of Tai Chi and Baduanjin on breast cancer patients: systematic review and meta-analysis of randomized controlled trials

BackgroundTai Chi and Baduanjin are nonpharmacological interventions that are widely applied among cancer patients.ObjectiveThis meta-analysis aimed to assess the effect of Tai Chi and Baduanjin on breast cancer patients by summarizing and pooling the results of previous studies.MethodsThe PubMed, Embase, Web of Science, Scopus and Cochrane Library and several databases were searched up to December 1, 2023, to identify high-quality RCTs. Relevant terms such as Tai Chi and Baduanjin were used as keywords. Stata 15.0 software and Review Manager (version 5.3; Cochrane Training) were used to screen the studies, extract the data, code the data, and perform the meta-analysis. The mean differences (MDs) and standardized mean differences (SMDs) with 95% CIs were used to calculate continuous variables. The Cochrane risk of bias assessment tool was used to evaluate the risk of bias. The PICOS framework was used to develop the following eligibility criteria: (i) population - breast cancer patients; (ii) intervention - Tai Chi and Baduanjin intervention; (iii) comparison - Tai Chi and Baduanjin group and different intervention (e.g., regular intervention, routine rehabilitation training, waiting list, sham Qigong, usual care, no intervention); (iv) outcomes - cognitive ability, shoulder joint function, anxiety, depression, fatigue, sleep quality, quality of life; and (v) study design - randomized controlled trial.ResultsFrom January 2013 to December 2023, we included a total of 16 RCTs involving 1247 patients. A total of 647 patients were in the experimental group and were treated with Tai Chi and Baduanjin, while 600 patients were in the control group and were treated with traditional methods. The results of our meta-analysis indicate that Tai Chi and Baduanjin yield outcomes that are comparable to those of traditional treatment methods. Specifically, Tai Chi and Baduanjin significantly increased cognitive function, increased shoulder joint function, improved sleep quality indicators and improved quality of life indicators. Furthermore, Tai Chi and Baduanjin significantly reduced anxiety symptoms, depression symptoms, and fatigue symptoms among breast cancer patients. Sensitivity analysis was performed, a funnel plot was constructed. No publication bias was indicated by Egger’s or Begg’s test.ConclusionOverall, Tai Chi and Baduanjin are viable and effective nonpharmacological approaches for treating breast cancer patients, as they yield better results than traditional treatment methods. However, these findings should be interpreted with caution due to the limited number of controlled trials, small sample sizes, and low quality of the evidence.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023469301.

Significance of LIF/LIFR Signaling in the Progression of Obesity-Driven Triple-Negative Breast Cancer

American women with obesity have an increased incidence of triple-negative breast cancer (TNBC). The impact of obesity conditions on the tumor microenvironment is suspected to accelerate TNBC progression; however, the specific mechanism(s) remains elusive. This study explores the hypothesis that obesity upregulates leukemia inhibitory factor receptor (LIFR) oncogenic signaling in TNBC and assesses the efficacy of LIFR inhibition with EC359 in blocking TNBC progression. TNBC cell lines were co-cultured with human primary adipocytes, or adipocyte-conditioned medium, and treated with EC359. The effects of adiposity were measured using cell viability, colony formation, and invasion assays. Mechanistic studies utilized RNA-Seq, Western blotting, RT-qPCR, and reporter gene assays. The therapeutic potential of EC359 was tested using xenograft and patient-derived organoid (PDO) models. The results showed that adipose conditions increased TNBC cell proliferation and invasion, and these effects correlated with enhanced LIFR signaling. Accordingly, EC359 treatment reduced cell viability, colony formation, and invasion under adipose conditions and blocked adipose-mediated organoid growth and TNBC xenograft tumor growth. RNA-Seq analysis identified critical pathways modulated by LIF/LIFR signaling in diet-induced obesity mouse models. These findings suggest that adiposity contributes to TNBC progression via the activation of the LIF/LIFR pathway, and LIFR inhibition with EC359 represents a promising therapeutic approach for obesity-associated TNBC.