Cancer Screening in Low- and Middle-Income Countries.

The worldwide cancer burden is growing, and populations residing in low- and middle-income countries (LMICs) are experiencing a disproportionate extent of this growth. Breast, colorectal, and cervical cancers are among the top 10 most frequently diagnosed malignancies, and they also account for a substantial degree of cancer mortality internationally. Effective screening strategies are available for all three of these cancers. Individuals from LMICs face substantial cost and access barriers to early detection programs, and late stage at diagnosis continues to be a major cause for cancer mortality in these communities. This chapter will review the epidemiology of breast, colorectal, and cervical cancers, and will explore prospects for improving global control through novel approaches to screening in cost-constrained environments.

Breast cancer in women by HIV status: A report from the South African National Cancer Registry.

BACKGROUND: Breast cancer (BC) is the leading cause of cancer-related morbidity and mortality in women living in South Africa, a country with a high HIV burden. However, characteristics of the double burden of HIV and BC in South Africa have not been properly investigated. We described characteristics of BC cases by HIV status in South Africa. METHODS: In this nationwide South African study, we obtained BC records for women aged ≥15 years diagnosed in the public health sector between January 2004 and December 2014. We included records from the National Cancer Registry that had been linked to HIV-related laboratory records from the National Health Laboratory Service. We assessed the odds of being HIV positive versus HIV negative in relation to patient-, cancer-, and municipality-related characteristics. RESULTS: From 2004-2014, 40 520 BC cases were diagnosed in women aged ≥15 years. Of these, 73.5% had unknown HIV status, 18.7% were HIV negative, and 7.7% were HIV positive. The median age at BC diagnosis was 43 years (interquartile range [IQR]: 37-52) in HIV positive and 57 years (IQR: 46-68) in HIV negative women, respectively. The odds of being HIV positive was higher for women who were aged 30-34 years compared to women aged 35-39 years at cancer diagnosis (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.10-1.71), Black versus non-Black (OR 6.41, 95% CI 5.68-7.23), diagnosed with cancer in rural versus urban areas (OR 1.59, 95% CI 1.40-1.82) and diagnosed in municipalities with low and middle (OR 3.46, 95% CI 2.48-4.82) versus high socioeconomic position (OR 2.69, 95% CI 2.11-3.42). CONCLUSION: HIV status was unknown for the majority of BC patients. Among those with known HIV status, being HIV positive was associated with a younger age at cancer diagnosis, being Black and receiving care in municipalities of poor socioeconomic position. Future studies should examine opportunities to integrate HIV and BC control programs.

Women's Preventive Services Utilization in Illinois in the Aftermath of the ACA and the COVID-19 Pandemic.

This study explores the association between health system changes over the last decade and women's preventive care utilization in Illinois. A cross-sectional analysis using Illinois Behavioral Risk Factor Surveillance System (BRFSS) data from 2012-2020 among women aged 21-75 (n=21,258) examined well-woman visit (WWV) receipt and breast and cervical cancer screening overall and over several time periods. There was an increase in the prevalence of receiving a WWV for Illinois women overall from 2012-2020. However, the overall adjusted prevalence difference was only significant for the 2020 versus 2015-2019 comparison and not for 2015-2019 versus 2012-2014. The COVID-19 pandemic was not associated with a decrease in the prevalence of mammogram use but was manifest for cervical cancer screening, particularly for Black women. Finally, those reporting having a WWV in the past year had a significantly higher prevalence of being up to date with screening compared with those not reporting a WWV.

Reproductive characteristics, menopausal status, race and ethnicity, and risk of breast cancer subtypes defined by ER, PR and HER2 status: the Breast Cancer Etiology in Minorities study.

BACKGROUND: Associations between reproductive factors and risk of breast cancer differ by subtype defined by joint estrogen receptor (ER), progesterone receptor (PR), and HER2 expression status. Racial and ethnic differences in the incidence of breast cancer subtypes suggest etiologic heterogeneity, yet data are limited because most studies have included non-Hispanic White women only. METHODS: We analyzed harmonized data for 2,794 breast cancer cases and 4,579 controls, of whom 90% self-identified as African American, Asian American or Hispanic. Questionnaire data were pooled from three population-based studies conducted in California and data on tumor characteristics were obtained from the California Cancer Registry. The study sample included 1,530 luminal A (ER-positive and/or PR-positive, HER2-negative), 442 luminal B (ER-positive and/or PR-positive, HER2-positive), 578 triple-negative (TN; ER-negative, PR-negative, HER2-negative), and 244 HER2-enriched (ER-negative, PR-negative, HER2-positive) cases. We used multivariable unconditional logistic regression models to estimate subtype-specific ORs and 95% confidence intervals associated with parity, breast-feeding, and other reproductive characteristics by menopausal status and race and ethnicity. RESULTS: Subtype-specific associations with reproductive factors revealed some notable differences by menopausal status and race and ethnicity. Specifically, higher parity without breast-feeding was associated with higher risk of luminal A and TN subtypes among premenopausal African American women. In contrast, among Asian American and Hispanic women, regardless of menopausal status, higher parity with a breast-feeding history was associated with lower risk of luminal A subtype. Among premenopausal women only, luminal A subtype was associated with older age at first full-term pregnancy (FTP), longer interval between menarche and first FTP, and shorter interval since last FTP, with similar OR estimates across the three racial and ethnic groups. CONCLUSIONS: Subtype-specific associations with reproductive factors overall and by menopausal status, and race and ethnicity, showed some differences, underscoring that understanding etiologic heterogeneity in racially and ethnically diverse study samples is essential. Breast-feeding is likely the only reproductive factor that is potentially modifiable. Targeted efforts to promote and facilitate breast-feeding could help mitigate the adverse effects of higher parity among premenopausal African American women.

Assessing nutrition-related knowledge, attitudes, and practices towards breast cancer prevention among female students at the Federal University of Oye-Ekiti, Nigeria.

BACKGROUND: Breast cancer remains a complex disease and leading cause of cancer-related death in Nigerian women. Recently, the role of nutrition has been highlighted in the etiology of breast cancer. METHODS: The aim of this research was to evaluate the nutrition-related knowledge, attitude, and practices of female university students. We also investigated the correlation between their demographic characteristics and their knowledge and attitudes of the survey participants. A descriptive cross-sectional study was carried out among female students at the Federal University of Oye (FUOYE), Nigeria. Participants completed self-administered questionnaires designed to assess their knowledge, attitude, and practices concerning cancer prevention. Statistical analysis was performed using SPSS 20, and significance was set at p < 0.05. RESULTS: Out of the 402 students who received the questionnaire, 300 completed it. The average age of the participants was 21.26 years with a standard deviation of 2.68. There was generally limited knowledge regarding breast cancer risk factors, with 45% of participants citing family history as the most recognized risk factor. Overall, knowledge level was influenced by the participants' permanent place of residence and course of study. Attitudes towards the impact of maternal and paternal nutrition on breast cancer prevention were notably low. Additionally, less than half of the participants demonstrated good dietary practices. CONCLUSION: This study revealed low levels of nutrition-related knowledge concerning cancer prevention, accompanied by poor dietary habits among the participants. These results suggest a possible link between inadequate knowledge about breast cancer prevention and the observed poor dietary practices among the participants. The frequent consumption of unhealthy foods among the participants may be a pointer to higher risk of breast cancer in the future, emphasizing a need for health education targeted at this group.

Disease burden of breast cancer and risk factors in Europe 44 countries, 1990-2019: findings of the global burden of disease study 2019.

Background: Breast cancer (BC) represents a significant health challenge in Europe due to its elevated prevalence and heterogeneity. Despite notable progress in diagnostic and treatment methods, the region continues to grapple with rising BC burdens, with comprehensive investigations into this matter notably lacking. This study explores BC burden and potential contributing risk factors in 44 European countries from 1990 to 2019. The aim is to furnish evidence supporting the development of strategies for managing BC effectively. Methods: Disease burden estimates related to breast cancer from the Global Burden of Disease 2019(GBD2019) across Eastern, Central, and Western Europe were examined using Joinpoint regression for trends from 1990 to 2019. Linear regression models examined relationships between BC burden and Socio-demographic Index (SDI), healthcare access and quality (HAQ), and BC prevalence. We utilized disability-adjusted life year(DALY) proportions for each risk factor to depict BC risks. Results: In Europe, the BC burden was 463.2 cases per 100,000 people in 2019, 1.7 times the global burden. BC burden in women was significantly higher and increased with age. Age-standardized mortality and DALY rates of BC in Europe in 2019 decreased by 23.1%(average annual percent change: AAPC -0.92) and 25.9%(AAPC -1.02), respectively, compared to 1990, in line with global trends. From 1990 to 2019, age-standardized DALY declined faster in Western Europe (-34.8%, AAPC -1.49) than in Eastern Europe (-9.4%, AAPC -0.25) and Central Europe (-15.0%, AAPC -0.56). Monaco, Serbia, and Montenegro had the highest BC burden in Europe in 2019. BC burden was negatively correlated with HAQ. In addition, Alcohol use and Tobacco were significant risk factors for DALY. High fasting plasma glucose and obesity were also crucial risk factors that cannot be ignored in DALY. Conclusion: The burden of BC in Europe remains a significant health challenge, with regional variations despite an overall downward trend. Addressing the burden of BC in different regions of Europe and the increase of DALY caused by different risk factors, targeted prevention measures should be taken, especially the management of alcohol and tobacco should be strengthened, and screening services for BC should be popularized, and medical resources and technology allocation should be optimized.

Inflammatory bowel disease and breast cancer: A two-sample bidirectional Mendelian randomization study.

There is a correlation between IBD and breast cancer according to previous observational studies. However, so far there is no evidence to support if there is a causal relationship between these 2 diseases. We acquired comprehensive Genome-Wide Association Study (GWAS) summary data on IBD (including ulcerative colitis [UC] and Crohn disease [CD]) as well as breast cancer of completely European descent from the IEU GWAS database. The estimation of bidirectional causality between IBD (including UC and CD) and breast cancer was achieved through the utilization of 2-sample Mendelian randomization (MR). The MR results were also assessed for any potential bias caused by heterogeneity and pleiotropy through sensitivity analyses. Our study found a bidirectional causal effect between IBD and breast cancer. Genetic susceptibility to IBD was associated with an increased risk of breast cancer (OR = 1.053, 95% CI: 1.016-1.090, P = .004). Similarly, the presence of breast cancer may increase the risk of IBD (OR = 1.111, 95% CI: 1.035-1.194, P = .004). Moreover, the bidirectional causal effect between IBD and breast cancer can be confirmed by another GWAS of IBD. Subtype analysis showed that CD was associated with breast cancer (OR = 1.050, 95% CI: 1.020-1.080, P < .001), but not UC and breast cancer. There was a suggestive association between breast cancer and UC (OR = 1.106, 95% CI: 1.011-1.209, P = .028), but not with CD. This study supports a bidirectional causal effect between IBD and breast cancer. There appear to be considerable differences in the specific associations of UC and CD with AD. Understanding that IBD including its specific subtypes and breast cancer constitute common risk factors can contribute to the clinical management of both diseases.

Breast Cancer Management During the COVID Pandemic.

OBJECTIVE: To explore the impact of COVID-19 among both the newly diagnosed patients and patients under follow-up for breast cancer by focusing on patients' accessibility to management and comparing the distribution of them before and during pandemic. STUDY DESIGN: Single-centric retrospective study. Place and Duration of the Study: Department of General Surgery and Department of Physical Medicine and Rehabilitation, Atilim University, Medicana International Ankara Hospital, Ankara, Turkiye, from March 2018 to 2022. METHODOLOGY: The data were collected to analyse numbers and distributions of physician visits regarding breast cancer. RESULTS: The mean age of patients was 55.98 ± 12.60 years. The percentages of newly diagnosed cases showed similarity (7.37% vs. 9.79%) before and during the pandemic (p = 0.18).  The number of imaging studies decreased by 53.33% in patients under follow-up (p = 0.006), despite screening tests showed a similar trend (p = 0.145). General surgery visits marked up (+44.6%), in contrast to plastic surgery visits (-42.04%, p <0.001). Patients' admissions decreased in many COVID-19 related clinics (pulmonology, emergency, internal medicine, and intensive care), but cardiology (+96.59%) and rehabilitation (+75%) admissions increased during the pandemic (p <0.001). The number of medical oncology and radiation oncology visits did not change (p >0.05). CONCLUSION: Total number of physician visits was similar before and during the pandemic despite the changing distribution. While COVID-19 led to markedly rising trends of surgical, cardiological, and rehabilitative management in patients with breast cancer, falling trends were seen in other specialities except oncology which showed a plateau during two years. The falling trends of visits to pulmonology, emergency, internal medicine, and intensive care clinics may be explained by crowded COVID-19 cases. KEY WORDS: Breast cancer, COVID-19, Surgery, Oncology, Rehabilitation.

Determination of Breast Cancer Risk and Knowledge Levels in Women: The Case of Cyprus.

BACKGROUND: Breast cancer is the type of cancer that is seen all over the world and ranks first among female cancers in terms of incidence and cause of death. OBJECTIVE: This research was conducted to determine the breast cancer risk level and breast cancer knowledge level in women living in Northern Cyprus. METHODS: The study, which was planned as a relational survey, was carried out as web-based. The research was completed with 657 adult female participants living in Northern Cyprus who volunteered to participate in the study. In order to collect data, the first section includes the introductory features, the second section includes the "Breast Cancer Risk Assessment Form" for determining breast cancer risk levels, the third section includes the "Comprehensive Breast Cancer Knowledge Test" to determine the breast cancer knowledge levels of the participants, and the fourth section includes the "Champion Health Belief Model Scale" was used. RESULTS: It was determined that 95.2% of women were in the low risk group for breast cancer. The knowledge test mean score is 12.05, and it can be said that the scores obtained are above the average (min:4- max:18). It was found that 55.7% of the women knew how to do Breast Self-Examination (BSE), but only 15.4% of them regularly performed BSE every month. It was found that 80.9% of the women never had mammography and their knowledge scores increased with increasing education level (p< 0.001) and there was a significant relationship between non-smokers and their knowledge levels (p< 0.01). IMPLICATIONS FOR PRACTICE: Despite the high scores of women in knowledge tests, it was observed that the frequency of applying BSE and having mammography was very low. Regardless of the risk factors for breast cancer, the importance of regular check-ups and BSE for every woman should be taught to women by health professionals, and group trainings should be planned for women who do not have training on this subject.

Omicron neutralization character in patients with breast cancer and liver cancer after the nationwide omicron outbreak.

BACKGROUND: The surge in omicron variants has caused nationwide breakthrough infections in mainland China since the December 2022. In this study, we report the neutralization profiles of serum samples from the patients with breast cancer and the patients with liver cancer who had contracted subvariant breakthrough infections. METHODS: In this real-world study, we enrolled 143 COVID-19-vaccinated (81 and 62 patients with breast and liver cancers) and 105 unvaccinated patients with cancer (58 and 47 patients with breast and liver cancers) after omicron infection. Anti-spike receptor binding domain (RBD) IgGs and 50% pseudovirus neutralization titer (pVNT50) for the preceding (wild type), circulating omicron (BA.4-BA.5, and BF.7), and new subvariants (XBB.1.5) were comprehensively analyzed. RESULTS: Patients with liver cancer receiving booster doses had higher levels of anti-spike RBD IgG against circulating omicron (BA.4-BA.5, and BF.7) and a novel subvariant (XBB.1.5) compared to patients with breast cancer after breakthrough infection. Additionally, all vaccinated patients produced higher neutralizing antibody titers against circulating omicron (BA.4-BA.5, and BF.7) compared to unvaccinated patients. However, the unvaccinated patients produced higher neutralizing antibody against XBB.1.5 than vaccinated patients after Omicron infection, with this trend being more pronounced in breast cancer than in liver cancer patients. Moreover, we found that there was no correlation between anti-spike RBD IgG against wildtype virus and the neutralizing antibody titer, but a positive correlation between anti-spike RBD IgG and the neutralizing antibody against XBB.1.5 was found in unvaccinated patients. CONCLUSION: Our study found that there may be differences in vaccine response and protective effect against COVID-19 infection in patients with liver and breast cancer. Therefore, we recommend that COVID-19 vaccine strategies should be optimized based on vaccine components and immunology profiles of different patients with cancer.

Risk factors for secondary thyroid cancer in patients with breast cancer: a propensity­matched SEER analysis.

With the rapid development of imaging technology and comprehensive treatment in modern medicine, the early diagnosis rate of breast cancer is constantly improving, and the prognosis is also improving; As breast cancer patients survive longer, the risk of developing second primary cancers increases. Since both breast and thyroid are Hormone receptor sensitive organs, which are regulated by hypothalamus pituitary target gland endocrine axis, changes in body endocrine status may lead to the occurrence of these two diseases in succession or simultaneously. This study extracted clinical data and survival outcomes of breast cancer patients registered in the Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2019. After matching the case and controls with propensity scores, the selected patients were randomly split into training and test datasets at a ratio of 7:3. Univariate and multivariate COX proportional regression analysis is used to determine independent risk factors for secondary thyroid cancer and construct a column chart prediction model. Age, ethnicity, whether radiotherapy, tumor primary location, N stage, M stage were identified by Cox regression as independent factors affecting secondary thyroid cancer in patients with breast cancer patients, and a risk factor nomogram was established to predict patients' 3 and 5 year survival probabilities. The AUC values for 3 and 5 years in the training set were 0.713, 0.707, and the c-index was 0.693 (95% CI 0.67144, 0.71456), and the AUC values for 3 and 5 years in the validation set were 0.681, 0.681, and the c-index was 0.673 (95% CI 0.64164, 0.70436), respectively.

Germline mutations of breast cancer susceptibility genes through expanded genetic analysis in unselected Colombian patients.

BACKGROUND: In Colombia and worldwide, breast cancer (BC) is the most frequently diagnosed neoplasia and the leading cause of death from cancer among women. Studies predominantly involve hereditary and familial cases, demonstrating a gap in the literature regarding the identification of germline mutations in unselected patients from Latin-America. Identification of pathogenic/likely pathogenic (P/LP) variants is important for shaping national genetic analysis policies, genetic counseling, and early detection strategies. The present study included 400 women with unselected breast cancer (BC), in whom we analyzed ten genes, using Whole Exome Sequencing (WES), know to confer risk for BC, with the aim of determining the genomic profile of previously unreported P/LP variants in the affected population. Additionally, Multiplex Ligation-dependent Probe Amplification (MLPA) was performed to identify Large Genomic Rearrangements (LGRs) in the BRCA1/2 genes. To ascertain the functional impact of a recurrent intronic variant (ATM c.5496 + 2_5496 + 5delTAAG), a minigene assay was conducted. RESULTS: We ascertained the frequency of P/LP germline variants in BRCA2 (2.5%), ATM (1.25%), BRCA1 (0.75%), PALB2 (0.50%), CHEK2 (0.50%), BARD1 (0.25%), and RAD51D (0.25%) genes in the population of study. P/LP variants account for 6% of the total population analyzed. No LGRs were detected in our study. We identified 1.75% of recurrent variants in BRCA2 and ATM genes. One of them corresponds to the ATM c.5496 + 2_5496 + 5delTAAG. Functional validation of this variant demonstrated a splicing alteration probably modifying the Pincer domain and subsequent protein structure. CONCLUSION: This study described for the first time the genomic profile of ten risk genes in Colombian women with unselected BC. Our findings underscore the significance of population-based research, advocating the consideration of molecular testing in all women with cancer.

Development of a model to predict the age at breast cancer diagnosis in a global population.

Knowing the mean age at diagnosis of breast cancer (BC) in a country is important for setting up an efficient BC screening program. The aim of this study was to develop and validate a model to predict the mean age at diagnosis of BC at the country level. To develop the model, we used the CI5plus database from the IARC, which contains incidence data for 122 selected populations for a minimum of 15 consecutive years from 1993 to 2012 and data from the World Bank. The standard model was fitted with a generalized linear model with the age of the population, growth domestic product per capita (GDPPC) and fertility rate as fixed effects and continent as a random effect. The model was validated in registries of the Cancer Incidence in Five Continents that are not included in the CI5plus database (1st validation set: 1950-2012) and in the most recently released volume (2nd validation set: 2013-2017). The intercept of the model was 30.9 (27.8-34.1), and the regression coefficients for population age, GDPPC and fertility rate were 0.55 (95% CI: 0.53-0.58, p < 0.001), 0.46 (95% CI: 0.26-0.67, p < 0.001) and 1.62 (95% CI: 1.42-1.88, p < 0.001), respectively. The marginal R2 and conditional R2 were 0.22 and 0.81, respectively, suggesting that 81% percent of the variance in the mean age at diagnosis of BC was explained by the variance in population age, GDPPC and fertility rate through linear relationships. The model was highly accurate, as the correlations between the predicted age from the model and the observed mean age at diagnosis of BC were 0.64 and 0.89, respectively, and the mean relative error percentage errors were 5.2 and 3.1% for the 1st and 2nd validation sets, respectively. We developed a robust model based on population age and continent to predict the mean age at diagnosis of BC in populations. This tool could be used to implement BC screening in countries without prevention programs.

Cancer Registry Enrichment via Linkage with Hospital-Based Electronic Medical Records: A Pilot Investigation.

Background: Hospital electronic medical record (EMR) systems are becoming increasingly integrated for management of patient data, especially given recent policy changes issued by the Centers for Medicaid and Medicare Services. In addition to data management, these data provide evidence for patient-centered outcomes research for a range of diseases, including cancer. Integrating EMR patient data with existing disease registries strengthens all essential components for assuring optimal health outcomes. Objectives: To identify the mechanisms for extracting, linking, and processing hospital EMR data with the Florida Cancer Data System (FCDS); and to assess the completeness of existing registry treatment data as well as the potential for data enhancement. Methods: A partnership among the Florida Department of Health, FCDS, and a large Florida hospital system was established to develop methods for hospital EMR extraction and transmission. Records for admission years between 2007 and 2010 were extracted using ICD-9-CM codes as the trigger and were linked with the cancer registry for patients with invasive cancers of the breast. Results: A total of 11,506 unique patients were linked with a total of 12,804 unique breast tumors. Evaluation of existing registry treatment data against the hospital EMR produced a total of 5% of registry records with updated surgery information, 1% of records with updated radiation information, and 7% of records updated with chemotherapy information. Enhancement of registry treatment information was particularly affected by the availability of chemotherapy medications data. Conclusion: Hospital EMR linkages to cancer disease registries is feasible but challenged by lack of standards for data collection, coding and transmission, comprehensive description of available data, and the exclusion of certain hospital datasets. The FCDS standard treatment data variables are highly robust and complete but can be enhanced by the addition of detailed chemotherapy regimens that are commonly used in patient centered outcomes research.

Trends in chemotherapy use for early-stage breast cancer from 2006 to 2019.

BACKGROUND: Little is known about how use of chemotherapy has evolved in breast cancer patients. We therefore describe chemotherapy patterns for women with stage I-IIIA breast cancer in the Optimal Breast Cancer Chemotherapy Dosing (OBCD) Study using data from KPNC (Kaiser Permanente Northern California) and KPWA (Kaiser Permanente Washington). FINDINGS: Among 33,670 women, aged 18 + y, diagnosed with primary stage I-IIIA breast cancer at KPNC and KPWA from 2006 to 2019, we explored patterns of intravenous chemotherapy use, defined here as receipt of intravenous cytotoxic drugs and/or anti-HER2 therapies. We evaluated trends in chemotherapy receipt, duration over which chemotherapy was received, and number of associated infusion visits. In secondary analyses, we stratified by receipt of anti-HER2 therapies (trastuzumab and/or pertuzumab), given their longer duration. 38.9% received chemotherapy intravenously, declining from 40.2% in 2006 to 35.6% in 2019 (p-trend < 0.001). Among 13,089 women receiving chemotherapy, neoadjuvant treatment increased (4.1-14.7%; p-trend < 0.001), as did receipt of anti-HER2 therapies (20.8-30.9%) (p-trend < 0.001). The average treatment duration increased (5.3 to 6.0 months; p-trend < 0.001), as did the number of infusion visits (10.8 to 12.5; p-trend < 0.001). For those receiving anti-HER2 therapies, treatment duration and average number of visits decreased; among those not receiving anti-HER2 therapies, number of visits increased, with no change in duration. CONCLUSIONS: While the prevalence of chemotherapy receipt has decreased over time, the use of neoadjuvant chemotherapy has increased, as has use of anti-HER2 therapies; duration and number of administration visits have also increased. Understanding these trends is useful to inform clinical and administrative planning.

Mitochondrial DNA copy number mediated the associations between perfluoroalkyl substances and breast cancer incidence: A prospective case-cohort study.

Epidemiologic studies have reported the relationships between perfluoroalkyl substances (PFASs) and breast cancer incidence, yet the underlying mechanisms are not well understood. This study aimed to elucidate the mediation role of mitochondrial DNA copy number (mtDNAcn) in the relationships between PFASs exposure and breast cancer risk. We conducted a case-cohort study within the Dongfeng-Tongji cohort, involving 226 incident breast cancer cases and a random sub-cohort (n = 990). Their plasma concentrations of six PFASs [including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroheptanoic acid (PFHpA), perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS)], and peripheral blood levels of mtDNAcn, were detected at baseline by using ultraperformance liquid chromatography-tandem mass spectrometry and quantitative real-time PCR, respectively. Linear regression and Barlow-weighted Cox models were employed separately to assess the relationships of mtDNAcn with PFASs and breast cancer risk. Mediation analysis was further conducted to quantify the mediating effects of mtDNAcn on PFAS-breast cancer relationships. We observed increased blood mtDNAcn levels among participants with the highest PFNA and PFHpA exposure [Q4 vs. Q1, ß(95%CI) = 0.092(0.022, 0.162) and 0.091(0.022, 0.160), respectively], while no significant associations were observed of PFOA, PFDA, PFOS, or PFHxS with mtDNAcn. Compared to participants within the lowest quartile subgroup of mtDNAcn, those with the highest mtDNAcn levels exhibited a significantly increased risk of breast cancer and postmenopausal breast cancer [Q4 vs. Q1, HR(95%CI) = 3.34(1.80, 6.20) and 3.71(1.89, 7.31)]. Furthermore, mtDNAcn could mediate 14.6 % of the PFHpA-breast cancer relationship [Indirect effect, HR(95%CI) = 1.02(1.00, 1.05)]. Our study unveiled the relationships of PFNA and the short-chain PFHpA with mtDNAcn and the mediation role of mtDNAcn in the PFHpA-breast cancer association. These findings provided insights into the potential biological mechanisms linking PFASs to breast cancer risk.

Association between triglyceride glucose index and breast cancer in 142,184 Chinese adults: findings from the REACTION study.

Background: The triglyceride glucose (TyG) index has been associated with an increased risk in breast cancer. However, this association remains unclear among the Chinese population. This study aimed to investigate whether the TyG index is associated with the risk of prevalent breast cancer in Chinese women. Methods: This cross-sectional study included 142,184 women from the REACTION (Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal) Study, which recruited adults aged 40 years or older from 25 centers across mainland China between 2011 and 2012. The TyG index was calculated according to the formula: Ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Multivariable-adjusted logistic regression models were used to evaluate odds ratios (ORs) and 95% confidence intervals (CIs) regarding the associations between the TyG index and breast cancer. Results: Multivariable-adjusted logistic regression analysis showed that compared with the lowest quartile of the TyG index, the highest quartile of the TyG index was significantly associated with an increased risk of prevalent breast cancer, with an OR (95% CI) of 1.61 (1.19-2.17). In the stratified analysis, the association of each 1 SD increase in the TyG index with risk of prevalent breast cancer was more dominant in individuals with menarche at age 13-17, those who were postmenopausal, those with a history of breastfeeding, and those who had two to four children, with the ORs (95% CIs) of 1.35 (1.09-1.68), 1.27 (1.05-1.54), 1.26 (1.05-1.52), and 1.32 (1.08-1.62), respectively. Moreover, among those without discernible insulin resistance (homeostatic model assessment-insulin resistance [HOMA-IR] ≥2.5), hyperglycemia and dyslipidemia, each 1 SD increase in the TyG index was associated with a 1.36-fold increase in breast cancer risk, with an OR (95% CI) of 2.36 (1.44-3.87). Conclusion: The TyG index is significantly associated with the prevalent breast cancer risk among middle-aged and elderly Chinese women.

Exposure to Pesticides and Breast Cancer in an Agricultural Region in Brazil.

Rural workers are disproportionally exposed to pesticides and might be at an increased risk of developing chronic diseases. Here, we investigated the impact of pesticide exposure on breast cancer (BC) risk and disease profile in rural female workers. This is a case-control study that prospectively included 758 individuals. The study was conducted in the Southwest region of Paraná state in Brazil, a region characterized by family-based agriculture and intensive use of pesticides. We found that this region has a 41% higher BC diagnosis rate and 14% higher BC mortality rate than the mean rates in Brazil, as well as a pesticide trade volume about 6 times higher than the national average. We showed substantial exposure in this population and found that even women who did not work in the fields but performed equipment decontamination and clothes washing of male partners who worked in the fields had urine samples positive for glyphosate, atrazine, and/or 2,4-D. The crude association showed a significantly higher risk of BC among women exposed to pesticides (OR: 1.58, 95% CI 1.18-2.13). Adjusted analyses showed a lower and nonstatistically significant association (OR: 1.30, 95% CI 41 0.87-1.95). Stratification on disease profile showed a significantly higher risk of lymph node metastasis (adjusted OR: 2.19, 95% CI 1.31-3.72) in women exposed to pesticides. Our findings suggest that female populations exposed to pesticides are at a higher risk of developing BC with a more aggressive profile and draw attention to the need to monitor rural populations potentially exposed to pesticides in the field or at home.

Assessment of BRCA1 and BRCA2 Germline Variant Data From Patients With Breast Cancer in a Real-World Data Registry.

PURPOSE: The emergence of large real-world clinical databases and tools to mine electronic medical records has allowed for an unprecedented look at large data sets with clinical and epidemiologic correlates. In clinical cancer genetics, real-world databases allow for the investigation of prevalence and effectiveness of prevention strategies and targeted treatments and for the identification of barriers to better outcomes. However, real-world data sets have inherent biases and problems (eg, selection bias, incomplete data, measurement error) that may hamper adequate analysis and affect statistical power. METHODS: Here, we leverage a real-world clinical data set from a large health network for patients with breast cancer tested for variants in BRCA1 and BRCA2 (N = 12,423). We conducted data cleaning and harmonization, cross-referenced with publicly available databases, performed variant reassessment and functional assays, and used functional data to inform a variant's clinical significance applying American College of Medical Geneticists and the Association of Molecular Pathology guidelines. RESULTS: In the cohort, White and Black patients were over-represented, whereas non-White Hispanic and Asian patients were under-represented. Incorrect or missing variant designations were the most significant contributor to data loss. While manual curation corrected many incorrect designations, a sizable fraction of patient carriers remained with incorrect or missing variant designations. Despite the large number of patients with clinical significance not reported, original reported clinical significance assessments were accurate. Reassessment of variants in which clinical significance was not reported led to a marked improvement in data quality. CONCLUSION: We identify the most common issues with BRCA1 and BRCA2 testing data entry and suggest approaches to minimize data loss and keep interpretation of clinical significance of variants up to date.

Screening for hepatitis C virus at the time of mammography using rapid diagnostic tests in women aged between 50 and 74 years (Mamm'OC NCT05067374).

Chronic hepatitis C Virus (HCV) infection presents a global health challenge, with significant morbidity and mortality worldwide. Despite remarkable progress in treatment options, achieving elimination targets by 2030, as set by the World Health Organization, remains elusive. Our study aimed to address this gap by integrating HCV screening into a national breast cancer screening program. Between March 2022 and March 2023, a prospective cross-sectional multicenter study was conducted in four radiology centers in Montpellier, France. We proposed HCV screening to consecutive women undergoing mammography, targeting 1,500 participants aged 50-74 years. A rapid diagnostic test (RDT) for HCV antibodies (HCV Ab) was performed on capillary whole blood, with positive cases undergoing serological and RNA confirmation. Participants also completed a questionnaire on demographic data and risk factors. Acceptance rates, HCV prevalence, and linkage to care were assessed. The acceptance rate for this integrated screening approach was 82.4%. Notably, the seroprevalence of HCV was found to be 0.65%. Linkage to care was prompt, and the cascade of care demonstrated successful treatment outcomes. Importantly, the majority of detected infections were successfully resolved. These findings underscore the feasibility and acceptability of integrating HCV screening with breast cancer screening programs providing updated prevalence data and valuable insights for refining future screening strategies.