Cancer Mortality In Women Research Articles

Cirurgia citorredutora no câncer de ovário: uma revisão integrativa

Ovarian cancer ranks fifth on the list of causes of cancer mortality in women. The most used therapeutic approach for this condition is cytoreductive surgery combined with chemotherapy. This review aims to analyze survival related to cytoreductive surgery in cases of ovarian cancer. This occurred through an integrative review of articles from 2018 to 2022, following the PRISMA criteria, in the PubMed database. In total, 32 articles were found and of these, 18 entered this review. Therefore, cytoreduction followed by platinum/taxane-based chemotherapy is the current standard treatment for ovarian cancer. Survival outcomes are inversely related to initial and residual tumor burden after surgery. It appears that cytoreductive surgery is a viable technique that has been associated with good patient outcomes, including a median survival rate of 53 months.

Hybrid segmentation and 3D Imaging: Comprehensive framework for breast cancer patient segmentation and classification based on digital breast tomosynthesis

Breast cancer is among the deadliest conditions and the second-leading reason for cancer mortality in women. Breast cells begin to develop into malignant, cancerous tumors, which is how breast cancer develops. Self-tests and routine professional examinations aid in early diagnosis, which increases the likelihood of surviving. A major difficulty for researchers is the categorization of breast cancer as a medical procedure. The prevailing aim of this research is the earlier recognition of breast cancer using 3D images and AI monitors. Initially, the mammogram images are collected and preprocessed to enhance the image quality. Noise removal is done using a Multistage Selective Convolution Filter (MSCF), contrast enhancement is done using an Enhanced Contrast Limited Adaptive Histogram (ECLAH), and an Improved Canny Operator (ICO) is employed for edge detection. Segmentation is done using the DENSE Squeeze Excitation Network (DENSE SE- Net). The preprocessed images are converted to 3D images using Digital Breast Tomosynthesis (DBT). From the hybrid segmented and 3D images, the objects are identified utilizing the You Only Look Once v7 (YOLO v7), and the images are classified into mild, medium, severe, and unaffected women using semi-supervised CNN (SS CNN). Finally, an AI monitor is used to monitor the patients. The simulation findings reveal that the suggested technique yields higher accuracy, precision, recall, and F1 score and better ROC characteristics than the existing approaches.

The American Cancer Society National Lung Cancer Roundtable strategic plan: Lung cancer in women.

Lung cancer in women is a modern epidemic and represents a global health crisis. Cigarette smoking remains the most important risk factor for lung cancer in all patients and, among women globally, rates of smoking continue to increase. Although some data exist supporting sex-based differences across the continuum of lung cancer, there is currently a dearth of research exploring the differences in risk, biology, and treatment outcomes in women. Consequently, the American Cancer Society National Lung Cancer Roundtable recognizes the urgent need to promote awareness and future research that will close the knowledge gaps regarding lung cancer in women. To this end, the American Cancer Society National Lung Cancer Roundtable Task Group on Lung Cancer in Women convened a summit undertaking the following to: (1) summarize existing evidence and identify knowledge gaps surrounding the epidemiology, risk factors, biologic differences, and outcomes of lung cancer in women; (2) develop and prioritize research topics and questions that address research gaps and advance knowledge to improve quality of care of lung cancer in women; and (3) propose strategies for future research. PLAIN LANGUAGE SUMMARY: Lung cancer is the leading cause of cancer mortality in women, and, despite comparatively lower exposures to occupational and environmental carcinogens compared with men, disproportionately higher lung cancer rates in women who ever smoked and women who never smoked call for increased awareness and research that will close the knowledge gaps regarding lung cancer in women.

Uptake of Breast Cancer Screening Practices in Low and Middle-Income Countries: A Systematic Review and Meta-Analysis.

Breast cancer is the most prevalent cancer worldwide and the leading cause of cancer mortality in women. Uptake of breast cancer screening and early-detection practices in low- and middle-income countries (LMICs) has not been synthesized. We aimed to systematically quantify uptake of breast cancer screening in LMICs. We performed a systematic review and meta-analysis of observational population-based studies that reported the uptake of screening or early-detection practices. We searched PubMed, Scopus, Embase, and Web of Knowledge databases to January 2024. We pooled data using random-effects meta-analysis, and explored heterogeneity using subgroup analyses. 174 population-based studies encompassing >78 million women were included. Pooled prevalence of self-reported uptake of screening mammography, self-reported having had clinical breast examination for screening, and self-reported regular breast self-examination (relevant for breast awareness in LMICs) were 22.7% (95% CI: 18.6-27.2), 23.1% (95% CI: 19.5-27.0), and 14.6% (95% CI: 11.6-17.9) respectively. Uptake of breast cancer screening practices was lowest in Africa and low and lower-middle income countries. Uptake of breast cancer screening practices remained stable over time or slightly decreased. Women who lived in rural area, were single, had lower income level, had low educational attainment, were unemployed, were uninsured and had no family history of breast cancer were generally least likely to self-report uptake of breast cancer screening. This meta-analysis identified concerningly low uptake of breast cancer screening practices in LMICs. Governments should prioritize developing context-appropriate strategies to address this low uptake to support population-level stage-shifting of breast cancer in LMICs.

Hormone replacement therapy and cancer mortality in women with 17 site-specific cancers: a cohort study using linked medical records

BackgroundThere is limited evidence on the safety of Hormone Replacement Therapy (HRT) in women with cancer. Therefore, we systematically examined HRT use and cancer-specific mortality in women with 17 site-specific cancers.MethodsWomen newly diagnosed with 17 site-specific cancers from 1998 to 2019, were identified from general practitioner (GP) records, hospital diagnoses or cancer registries in Scotland, Wales and England. Breast cancer patients were excluded because HRT is contraindicated in breast cancer patients. The primary outcome was time to cancer-specific mortality. Time-dependent Cox regression models were used to calculate adjusted hazard ratios (HR) and 95% confidence intervals (95% CIs) for cancer-specific mortality by systemic HRT use.ResultsThe combined cancer cohorts contained 182,589 women across 17 cancer sites. Overall 7% of patients used systemic HRT after their cancer diagnosis. There was no evidence that HRT users, compared with non-users, had higher cancer-specific mortality at any cancer site. In particular, no increase was observed in common cancers including lung (adjusted HR = 0.98 95% CI 0.90, 1.07), colorectal (adjusted HR = 0.79 95% CI 0.70, 0.90), and melanoma (adjusted HR = 0.77 95% CI 0.58, 1.02).ConclusionsWe observed no evidence of increased cancer-specific mortality in women with a range of cancers (excluding breast) receiving HRT.

Effect of metabolic syndrome and its components on the risk and prognosis of cervical cancer: A literature review

Despite the global implementation of preventive strategies against Human Papilloma Virus (HPV) infection, the incidence of invasive cervical cancer rose by nearly 1.3-fold, from 471,000 annual cases in 2000 to 604,000 cases in 2020. With over 340,000 deaths annually, cervical cancer is the fourth leading cause of cancer mortality in women globally.There is a need to understand other factors besides HPV such as metabolic syndrome (MetS) that potentially influence the onset and progression of cervical cancer. In this narrative review, we describe evidence showing that Metabolic syndrome (MetS) increases the risk for cervical cancer and worsens its prognosis. Combined screening for MetS and cervical cancer has potential to significantly reduce morbidity and mortality in women with cervical cancer.

Breast Cancer Drugs Screening Model Based on Graph Convolutional Network and Ensemble Method

Breast cancer is the first cancer incidence and the second cancer mortality in women. Therefore, for the life and health of breast cancer patients, the research and development of breast cancer drugs should be accelerated. In drug development, the search for compounds with good bioactivity, pharmacokinetics, and safety, including Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET), has always been a time-consuming and labor-intensive process. In this paper, the relationship between the molecular descriptor and ADMET properties of compounds is studied. Aiming at the problem of composite ADMET attribute classification, a Stacking Algorithm based on Graph Convolutional Network (SA-GCN) was proposed. Firstly, feature selection was performed in the data of molecular descriptors. Then the SA-GCN is developed by integrating the advantages of ten classical classification algorithms. Finally, various performance indicators were used to conduct comparative experiments. Experiments show that the SA-GCN is superior to other classifiers in the classification performance of ADMET, and the classification accuracy is 97.6391%, 98.1450%, 94.4351%, 96.4587%, and 97.9764% compared to other classifiers. Therefore, this method can be well applied to the classification of ADMET properties of compounds and then could provide some help to screen out compounds with good biological activities.

Breast cancer recurrence rate after mastectomy in young females.

e12591 Background: Breast cancer is the most commonly diagnosed female cancer worldwide and the most common cause of cancer mortality in women. Surgical treatment of early breast cancer includes lumpectomy or mastectomy with or without reconstruction. Despite the surgeon’s best effort to perform a radical resection of the breast tissue during mastectomy to achieve locoregional control, residual fibroglandular tissue was found in 20% of breasts on postoperative breast MRI, which carries a risk of recurrence. Younger women with breast cancer have inferior survival rates despite receiving more aggressive therapy. Tumors in young women are more likely to be poorly differentiated, hormone receptor-negative, have a high proliferation index, and more lymphovascular invasion, which is partially explained by patients’ genetic profile. Another factor that could contribute to poor outcomes is the advanced stage at the time of diagnosis, including larger tumor size and higher rates of axillary lymph node positivity. This knowledge has motivated us to conduct this study that is dedicated to looking at the recurrence rate in young females following mastectomy. Methods: This is a retrospective study that collected data from young female patients who were diagnosed with breast cancer between January 2010 and August 2018, had an age at diagnosis of 18-45 years old, and underwent unilateral or bilateral mastectomy with or without reconstruction. The study also looked at the patient’s risk factors and genetic profile. Results: A total of 115 patients were diagnosed with early-stage breast cancer between January 2010 and August 2018 and underwent mastectomy. 81.74% were Caucasian females, and 8.7% were African American females. The mean age of diagnosis was 36.9 years. The mean BMI was 30.5 kg/m2. 59.13% of patients had a family history of breast cancer. The most common genetic mutations were BRCA1 at 7.83% and BRCA2 at 8.7%. 71% of patients underwent a bilateral mastectomy. 76% of patients had reconstruction. 77% of tumors were ER-positive, 68% PR-positive, and 26% HER2-positive. 49.4% of tumors were Nottingham grade 3. 52% of patients had no nodal involvement, while 35% had N1 disease. 34.6% had lymphovascular invasion. We found that 18/115 patients had recurrence of breast cancer following mastectomy. 5/17 patients had locoregional recurrence, while 12/17 patients had a distant recurrence; 1 patient’s recurrence data was unavailable. The median time to recurrence was 1147.5 days (335 to 3107). The 5-year recurrence free survival rate is 86% ± 3%. Conclusions: Our study found that 15.65% of young females had recurrence after mastectomy. To our knowledge, this is the first dedicated study to look at the recurrence rate after mastectomy in this young, high-risk patient population. Our study aims to encourage larger studies in young females with breast cancer to help tailor the treatment plan in this population.

Impact of the universal health insurance benefits on cervical cancer mortality in Colombia

BackgroundCervical cancer patients in Colombia have a lower likelihood of survival compared to breast cancer patients. In 1993, Colombia enrolled citizens in one of two health insurance regimes (contributory-private insurance and subsidized- public insurance) with fewer benefits in the subsidized regime. In 2008, the Constitutional Court required the Colombian government to unify services of both regimes by 2012. This study evaluated the impact of this insurance change on cervical cancer mortality before and after 2012.MethodsWe accessed 24,491 cervical cancer mortality records for 2006–2020 from the vital statistics of Colombia’s National Administrative Department of Statistics (DANE). We calculated crude mortality rates by health insurance type and departments (geopolitical division). Changes by department were analyzed by rate differences between 2006 and 2012 and 2013–2020, for each health insurance type. We analyzed trends using join-point regressions by health insurance and the two time-periods.ResultsThe contributory regime (private insurance) exhibited a significant decline in cervical cancer mortality from 2006 to 2012, characterized by a noteworthy average annual percentage change (AAPC) of -3.27% (P = 0.02; 95% CI [-5.81, -0.65]), followed by a marginal non-significant increase from 2013 to 2020 (AAPC 0.08%; P = 0.92; 95% CI [-1.63, 1.82]). In the subsidized regime (public insurance), there is a non-significant decrease in mortality between 2006 and 2012 (AAPC − 0.29%; P = 0.76; 95% CI [-2.17, 1.62]), followed by a significant increase from 2013 to 2020 (AAPC of 2.28%; P < 0.001; 95% CI [1.21, 3.36]). Examining departments from 2013 to 2020 versus 2006 to 2012, the subsidized regime showed fewer cervical cancer-related deaths in 5 out of 32 departments, while 6 departments had higher mortality. In 21 departments, mortality rates remained similar between both regimes.ConclusionImprovement of health benefits of the subsidized regime did not show a positive impact on cervical cancer mortality in women enrolled in this health insurance scheme, possibly due to unresolved administrative and socioeconomic barriers that hinder access to quality cancer screening and treatment.

Comparing the HER2 Status of the Primary Tumor to That of Disseminated Tumor Cells in Early Breast Cancer.

Breast cancer remains a leading cause of cancer mortality in women globally. Despite advancements in systemic therapy, the risk of distant recurrence persists even after such treatment and may be linked to disseminated tumor cells (DTCs). Variability in molecular characteristics between primary tumors (PTs) and distant metastases underscores the need to comprehensively understand metastatic pathways. This retrospective study investigated discrepancies between HER2 expression in PTs and DTCs and their implications for survival outcomes in 201 early breast cancer (EBC) patients. We found a significant association between HER2 expression in PTs and DTCs when classifying tumors as HER2-high/low/negative. Patients whose HER2 status was discordant between PTs and DTCs exhibited worse distant disease-free survival than those with concordant status. Multivariate analysis confirmed the HER2 status of DTCs as an independent prognostic factor for distant DFS. These findings emphasize the importance of assessing HER2 expression in DTCs and its potential implications for tailored therapy strategies in EBC. Furthermore, prospective trials are needed to validate these findings and explore targeted therapies based on the molecular characteristics of DTCs.

Advancing Immediate Breast Reconstruction Surgery in Pakistan: Bridging Literature Gaps and Meeting Patient Needs

Breast cancer ranks as the most diagnosed cancer globally and the leading cause of cancer mortality in women, with Pakistan exhibiting a particularly high incidence. However, breast reconstruction surgery, a critical intervention post-mastectomy, remains underutilized in Pakistan due to various barriers. Recent studies shed light on patient perspectives and outcomes regarding immediate breast reconstruction (IBR), indicating its positive impact on psychosocial well-being. Despite these insights, significant literature gaps persist, including the need for comprehensive national data, addressing cultural and awareness barriers, improving access and education, and prioritizing patient-centered care. This short communication underscores the urgency of addressing these gaps to advance breast reconstruction surgery in Pakistan. By conducting comprehensive studies, tackling cultural barriers, and prioritizing patient-centered care, we can ensure improved care and quality of life for Pakistani breast cancer patients. This call to action aims to transform the landscape of breast reconstruction surgery in Pakistan, offering hope for a brighter future for patients.

The PI3K/AKT/mTOR signaling pathway in breast cancer: Review of clinical trials and latest advances.

Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer mortality in women. As the phosphatidylinositol 3-kinase (PI3K) signaling pathway is involved in a wide range of physiological functions of cells including growth, proliferation, motility, and angiogenesis, any alteration in this axis could induce oncogenic features; therefore, numerous preclinical and clinical studies assessed agents able to inhibit the components of this pathway in BC patients. To the best of our knowledge, this is the first study that analyzed all the registered clinical trials investigating safety and efficacy of the PI3K/AKT/mTOR axis inhibitors in BC. Of note, we found that the trends of PI3K inhibitors in recent years were superior as compared with the inhibitors of either AKT or mTOR. However, most of the trials entering phase III and IV used mTOR inhibitors (majorly Everolimus) followed by PI3K inhibitors (majorly Alpelisib) leading to the FDA approval of these drugs in the BC context. Despite favorable efficacies, our analysis shows that the majority of trials are utilizing PI3K pathway inhibitors in combination with hormone therapy and chemotherapy; implying monotherapy cannot yield huge clinical benefits, at least partly, due to the activation of compensatory mechanisms. To emphasize the beneficial effects of these inhibitors in combined-modal strategies, we also reviewed recent studies which investigated the conjugation of nanocarriers with PI3K inhibitors to reduce harmful toxicities, increase the local concentration, and improve their efficacies in the context of BC therapy.

Evaluation of diagnostic value of Doppler ultrasound in the diagnosis of malignant breast masses.

Breast cancer is the leading cause of cancer mortality in women, and it is on the rise in Iran. Therefore, an early-stage diagnosis of breast cancer is of critical importance. Because ultrasound is one of the available, inexpensive, and minimally invasive techniques for distinguishing malignant from benign masses, a comparison of conventional ultrasound, color Doppler, and spectral Doppler findings can be useful. The purpose of this study was to determine the diagnostic value of sonographic indices, specifically Doppler parameters, in identifying the nature of breast masses. This is a cross-sectional study, with diagnostic value analysis. Before undergoing a biopsy, 80 patients with breast masses underwent B-mode and Doppler breast ultrasound. The ultrasound findings were then compared to pathologic results to determine which groups were malignant or benign. The resulting data were analyzed using statistical tests and diagnostic values with SPSS 22 software. B-mode grey-scale ultrasound indices such as mass shape, mass margin, mass orientation, and posterior features, as well as Doppler indices such as vascularity, RI (Resistive Index), PI (Pulsatility Index), and PSV (Peak Systolic Velocity), were found to be statistically significant with pathological findings. Color Doppler revealed vascularity in 65% of benign and 84% of malignant masses. The diagnostic value results revealed that mass shape, mass margin, mass orientation, and posterior features all play a significant role in predicting lesion malignancy, with a sensitivity of 92%, 58%, 64%, 56%, and specificity of 59%, 66%, 82%, and 84%, respectively. The RI, PI, and PSV indices were significantly higher in malignant masses, and all of them had remarkable diagnostic values in predicting malignancy, with a (Area Under The Curve) AUC of 0.863, 0.882, 0.702, a sensitivity of 84% and 84%, 68%, and a specificity of 83%, 86%, and 62%, respectively, at the optimal cut-off points (0.65, 1.32, 12.40) obtained from the Receiver Operating Characteristics (ROC) curves.

Abstract 801: Severe housing cost burden and premature cancer mortality by state Medicaid expansion status

Abstract Introduction: The fraction of people living in unaffordable housing in the U.S. has grown, and prior studies have documented a relationship between housing cost burden and worsening health. Medicaid expansion has been suggested to improve housing financial stability by reducing health care costs and improving access to preventative care. However, the role of expanded access to Medicaid on the relationship between housing cost burden and cancer mortality remains poorly understood. We investigated the relationship between county-level severe housing cost burden and premature cancer mortality by state Medicaid expansion status for all cancers and leading sites. Methods: This ecological study used county-level data from 2016-2020 American Community Survey linked with county-level mortality data. Severe housing cost burden measured by percentage of households within a county that spend ≥50% of their income on housing categorized into quintiles (1=lowest, 5=highest) and state Medicaid expansion status (expanded and non-expanded). Age-adjusted cancer mortality rates and adjusted-mortality rate ratio (aRR) were estimated by sex. Results: Across quintiles of county-level severe housing cost burden, age-adjusted cancer mortality rates were largely greater in non-Medicaid expanded states than Medicaid expanded states among women and men. Among counties in the lowest quintile of severe housing cost burden, rates for overall cancer mortality in women were 9% (aRR=1.09; 95%CI 1.05-1.14) higher in non-Medicaid expanded states compared with expanded states. Additionally, among the third quintile of severe housing cost burden, colorectal cancer mortality rate was 8% higher (aRR=1.08; 95%CI 1.02-1.14) in non-Medicaid expanded states. Among men in the lowest quintile of severe housing cost burden, overall cancer mortality rates were 5% (aRR=1.05; 95%CI 1.02-1.09) higher in non-Medicaid expanded states than Medicaid expanded states. Further, among men in counties in the highest quintile of severe housing cost burden, colorectal cancer mortality rate was 8% higher (aRR=1.08; 95%CI 1.05-1.12) and lung cancer mortality was 13% higher (aRR=1.13; 95%CI 1.10-1.15) in non-Medicaid expanded states compared with expanded states. Conclusions: Counties with a lower fraction of households experiencing severe housing cost burden had greater premature cancer death rates within non-Medicaid expanded states than Medicaid expanded states. However, among men rates were also elevated in non-Medicaid expanded states in counties with the greatest severe housing cost burden. Citation Format: Wayne R. Lawrence, Neal D. Freedman, Jennifer K. McGee-Avila, Lee Mason, Yingxi Chen, Aldenise P. Ewing, Meredith S. Shiels. Severe housing cost burden and premature cancer mortality by state Medicaid expansion status [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 801.

MRI Surveillance and Breast Cancer Mortality in Women With BRCA1 and BRCA2 Sequence Variations

Magnetic resonance imaging (MRI) surveillance is offered to women with a pathogenic variant in the BRCA1 or BRCA2 gene who face a high lifetime risk of breast cancer. Surveillance with MRI is effective in downstaging breast cancers, but the association of MRI surveillance with mortality risk has not been well defined. To compare breast cancer mortality rates in women with a BRCA1 or BRCA2 sequence variation who entered an MRI surveillance program with those who did not. Women with a BRCA1 or BRCA2 sequence variation were identified from 59 participating centers in 11 countries. Participants completed a baseline questionnaire between 1995 and 2015 and a follow-up questionnaire every 2 years to document screening histories, incident cancers, and vital status. Women who had breast cancer, a screening MRI examination, or bilateral mastectomy prior to enrollment were excluded. Participants were followed up from age 30 years (or the date of the baseline questionnaire, whichever was later) until age 75 years, the last follow-up, or death from breast cancer. Data were analyzed from January 1 to July 31, 2023. Entrance into an MRI surveillance program. Cox proportional hazards modeling was used to estimate the hazard ratios (HRs) and 95% CIs for breast cancer mortality associated with MRI surveillance compared with no MRI surveillance using a time-dependent analysis. A total of 2488 women (mean [range] age at study entry 41.2 [30-69] years), with a sequence variation in the BRCA1 (n = 2004) or BRCA2 (n = 484) genes were included in the analysis. Of these participants, 1756 (70.6%) had at least 1 screening MRI examination and 732 women (29.4%) did not. After a mean follow-up of 9.2 years, 344 women (13.8%) developed breast cancer and 35 women (1.4%) died of breast cancer. The age-adjusted HRs for breast cancer mortality associated with entering an MRI surveillance program were 0.20 (95% CI, 0.10-0.43; P < .001) for women with BRCA1 sequence variations and 0.87 (95% CI, 0.10-17.25; P = .93) for women with BRCA2 sequence variations. Results of this cohort study suggest that among women with a BRCA1 sequence variation, MRI surveillance was associated with a significant reduction in breast cancer mortality compared with no MRI surveillance. Further studies of women with BRCA2 sequence variations are needed to ascertain these women obtain the same benefits associated with MRI surveillance.

Strain Elastography Fat-to-Lesion Index Is Associated with Mammography BI-RADS Grading, Biopsy, and Molecular Phenotype in Breast Cancer.

Breast cancer (BC) affects millions of women worldwide, causing over 500,000 deaths annually. It is the leading cause of cancer mortality in women, with 70% of deaths occurring in developing countries. Elastography, which evaluates tissue stiffness, is a promising real-time minimally invasive technique for BC diagnosis. This study assessed strain elastography (SE) and the fat-to-lesion (F/L) index for BC diagnosis. This prospective study included 216 women who underwent SE, ultrasound, mammography, and breast biopsy (108 malignant, 108 benign). Three expert radiologists performed imaging and biopsies. Mean F/L index was 3.70 ± 2.57 for benign biopsies and 18.10 ± 17.01 for malignant. We developed two predictive models: a logistic regression model with AUC 0.893, 79.63% sensitivity, 87.62% specificity, 86.9% positive predictive value (+PV), and 80.7% negative predictive value (-PV); and a neural network with AUC 0.902, 80.56% sensitivity, 88.57% specificity, 87.9% +PV, and 81.6% -PV. The optimal Youden F/L index cutoff was >5.76, with 84.26% sensitivity and specificity. The F/L index positively correlated with BI-RADS (Spearman's r = 0.073, p < 0.001) and differed among molecular subtypes (Kruskal-Wallis, p = 0.002). SE complements mammography for BC diagnosis. With adequate predictive capacity, SE is fast, minimally invasive, and useful when mammography is contraindicated.

Abstract B001: Does deep intronic splicing in breast cancer susceptibility genes contribute to breast cancer?

Abstract Breast cancer (BC) is the most common cancer and leading cause of cancer mortality in women. Average lifetime BC risk for a woman in the United States is 13%. However, pathogenic variants in BC susceptibility genes such as BRCA1/2, ATM, and RAD51C, or high polygenic risk scores substantially increase BC risk. Women with a family history of BC and/or ovarian cancer, BC &amp;lt; age 40, or BC and second primary tumor are considered high-risk with an increased likelihood of having a pathogenic variant in a BC susceptibility gene. Yet, more than 60% of women with high-risk BC test negative for coding variants. In these women, possible causal variation could be non-coding in deep intronic or regulatory regions, or cryptic structural variants (SV). To determine whether deep intronic splicing contributes to BC in high-risk women testing negative for pathogenic coding variants in BC genes, we analyzed the intronic sequences of 649 BRCA1/BRCA2 negative individuals with high-risk BC. The samples had undergone targeted capture sequencing of exons and introns of more than 100 target genes including ATM and RAD51C. From the 649 samples, we identified three intronic splicing variants in ATM and RAD51C in 10 samples (1.5%) that had SpliceAI delta scores &amp;gt;0.5 suggesting changes to splicing. One splicing donor gain variant, RAD51C c.145+246A&amp;gt;T, was found exclusively in women of self-reported African ancestry at a frequency of 0.047. In gnomAD, the variant was found exclusively in individuals of African ancestry at a frequency of 0.012. A 1.3-fold enrichment in variant frequency was observed in AFR women under 65 with breast cancer compared to age-matched cancer free controls in the All of Us dataset. Using lymphoblastoid-cell derived RNA from carriers of RAD51C c.145+246A&amp;gt;T, we performed RT-PCR and cDNA amplification targeting the exons surrounding the variant and observed a lengthened exon. Targeted amplicon sequencing also confirmed the presence of intronic sequence in the variant cDNA. The introduced intronic sequence contains a UGA stop codon 12 bp from the end of the exon which could led to loss of RAD51C function. We have created minigene vectors in the RHCglo background and are performing minigene splicing assays to validate the splicing changes in ATM due to intronic variants. Gene functional assays and association studies will be conducted to determine the functional effects and risk conferred by these variants. Understanding the level of contribution of deep intronic splicing in known BC susceptibility genes is critically important, as results impact sequencing offered to patients, and if positive, their medical management. Citation Format: Mwangala P. Akamandisa, Bradley Wubbenhorst, Kurt D'Andrea, Heather Symecko, Rhonda Gillette, Payal D. Shah, Angela R. Bradbury, Kara N. Maxwell, Susan M. Domchek, Katherine L. Nathanson. Does deep intronic splicing in breast cancer susceptibility genes contribute to breast cancer? [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr B001.

Gender differences, environmental pressures, tumor characteristics, and death rate in a lung cancer cohort: a seven-years Bayesian survival analysis using cancer registry data from a contaminated area in Italy.

In Taranto, Southern Italy, adverse impacts on the environment and human health due to industrial installations have been studied. In the literature, associations have been reported between gender, environmental factors, and lung cancer mortality in women and men. The aim of this study was to investigate the relationships between gender, residence in areas with high environmental pressures, bronchus/lung cancer characteristics, and death rate. Data from the Taranto Cancer Registry were used, including all women and men with invasive bronchus/lung cancer diagnosed between 1 January 2016 and 31 December 2020 and with follow-up to 31 December 2022. Bayesian mixed effects logistic and Cox regression models were fitted with the approach of integrated nested Laplace approximation, adjusting for patients and disease characteristics. A total of 2,535 person-years were observed. Male gender was associated with a higher prevalence of histological grade 3 (OR 2.45, 95% CrI 1.35-4.43) and lung squamous-cell carcinoma (OR 3.04, 95% CrI 1.97-4.69). Variables associated with higher death rate were male gender (HR 1.24, 95% CrI 1.07-1.43), pathological/clinical stage II (HR 2.49, 95% CrI 1.63-3.79), III (HR 3.40, 95% CrI 2.33-4.97), and IV (HR 8.21, 95% CrI 5.95-11.34), histological grade 3 (HR 1.80, 95% CrI 1.25-2.59), lung squamous-cell carcinoma (HR 1.18, 95% CrI 1.00-1.39), and small-cell lung cancer (HR 1.62, 95% CrI 1.31-1.99). Variables associated with lower death rate were other-type lung cancer (HR 0.65, 95% CrI 0.44-0.95), high immune checkpoint ligand expression (HR 0.75, 95% CrI 0.59-0.95), lung localization (HR 0.73, 95% CrI 0.62-0.86), and left localization (HR 0.85, 95% CrI 0.75-0.95). The results among patients with lung cancer did not show an association between residence in the contaminated site of national interest (SIN) and the prevalence of the above mentioned prognostic factors, nor between residence in SIN and death rate. The findings confirmed the independent prognostic values of different lung cancer characteristics. Even after adjusting for patients and disease characteristics, male gender appeared to be associated with a higher prevalence of poorly differentiated cancer and squamous-cell carcinoma, and with an increased death rate.

Environmental pressures, tumor characteristics, and death rate in a female breast cancer cohort: a seven-years Bayesian survival analysis using cancer registry data from a contaminated area in Italy.

In Taranto, Southern Italy, adverse impacts on the environment and human health due to industrial installations have been studied. In the literature, few associations have been reported between environmental factors and breast cancer mortality in women. The aim of this study was to investigate the relationships between residence in areas with high environmental pressures, female breast cancer characteristics, and death rate. Data from the Taranto Cancer Registry were used, including all women with invasive breast cancer diagnosed between 01 January 2015 and 31 December 2020 and with follow-up to 31 December 2021. Bayesian mixed effects logistic and Cox regression models were fitted with the approach of integrated nested Laplace approximation, adjusting for patients and disease characteristics. A total of 10,445 person-years were observed. Variables associated with higher death rate were residence in the contaminated site of national interest (SIN) (HR 1.22, 95% CrI 1.01-1.48), pathological/clinical stage III (HR 2.77, 95% CrI 1.93-3.97) and IV (HR 17.05, 95% CrI 11.94-24.34), histological grade 3 (HR 2.50, 95% CrI 1.20-5.23), Ki-67 proliferation index of 21-50% (HR 1.42, 95% CrI 1.10-1.83) and > 50% (HR 1.81, 95% CrI 1.29-2.55), and bilateral localization (HR 1.65, 95% CrI 1.01-2.68). Variables associated with lower death rate were estrogen and/or progesterone receptor positivity (HR 0.61, 95% CrI 0.45-0.81) and HER2/neu oncogene positivity (HR 0.59, 95% CrI 0.44-0.79). The findings confirmed the independent prognostic values of different female breast cancer characteristics. Even after adjusting for patients and disease characteristics, residence in the SIN of Taranto appeared to be associated with an increased death rate.

Upregulation of BRCA1 and 2 protein expression is associated with dysregulation in amino acids profiles in breast cancer

BackgroundThe prevalence of breast cancer (BC) is high among cancers in Egypt, ranking it the most common cause of cancer mortality in women. BRCA1 and BRCA2 tumor suppressors proteins have a specific relationship with BC. Plasma free amino acids levels (PFAAs) have been reported to exhibit altered profiles among cancer patients. Thus, the present study aims to examine the alteration of the PFAAs profiles and investigate their association with BRCA1 and 2 circulating levels in Egyptian females diagnosed with BC and in females with family history of BC to establish potential early detection strategies for BC.Methods and resultsThis study included 26 BC patients, 22 females with family history of BC (relatives) in addition to 38 healthy females as control group. Quantitative measurement of PFAAs was determined by the ion exchange separation method through high performance liquid chromatography. BRCA1 and BRCA2 concentrations were determined using ELISA. Our results showed PFAAs profiles in BC patients and in females with BC family history with significant upregulation in mean plasma levels of Alanine, Phenylalanine, Glutamate and Cysteine and downregulation of Taurine, Threonine, Serine, Glycine, Valine, Methionine and Histidine levels compared to controls. Also, a significant positive correlation was observed between plasma BRCA1 and Valine levels while a significant negative correlation was observed between BRCA2 and Lysine plasma levels.ConclusionPFAAs profile can potentially be used in early screening for BC patients and for susceptible females.