Influence of breast cancer risk factors on proliferation and DNA damage in human breast glandular tissues: role of intracellular estrogen levels, oxidative stress and estrogen biotransformation

Breast cancer etiology is associated with both proliferation and DNA damage induced by estrogens. Breast cancer risk factors (BCRF) such as body mass index (BMI), smoking, and intake of estrogen-active drugs were recently shown to influence intratissue estrogen levels. Thus, the aim of the present study was to investigate the influence of BCRF on estrogen-induced proliferation and DNA damage in 41 well-characterized breast glandular tissues derived from women without breast cancer. Influence of intramammary estrogen levels and BCRF on estrogen receptor (ESR) activation, ESR-related proliferation (indicated by levels of marker transcripts), oxidative stress (indicated by levels of GCLC transcript and oxidative derivatives of cholesterol), and levels of transcripts encoding enzymes involved in estrogen biotransformation was identified by multiple linear regression models. Metabolic fluxes to adducts of estrogens with DNA (E-DNA) were assessed by a metabolic network model (MNM) which was validated by comparison of calculated fluxes with data on methoxylated and glucuronidated estrogens determined by GC– and UHPLC–MS/MS. Intratissue estrogen levels significantly influenced ESR activation and fluxes to E-DNA within the MNM. Likewise, all BCRF directly and/or indirectly influenced ESR activation, proliferation, and key flux constraints influencing E-DNA (i.e., levels of estrogens, CYP1B1, SULT1A1, SULT1A2, and GSTP1). However, no unambiguous total effect of BCRF on proliferation became apparent. Furthermore, BMI was the only BCRF to indeed influence fluxes to E-DNA (via congruent adverse influence on levels of estrogens, CYP1B1 and SULT1A2).

A Review of Breast Cancer Risk Factors in Adolescents and Young Adults

Cancer in adolescents and young adults (AYAs) deserves special consideration for several reasons. AYA cancers encompass paediatric malignancies that present at an older age than expected, or early-onset of cancers that are typically observed in adults. However, disease diagnosed in the AYA population is distinct to those same cancers which are diagnosed in a paediatric or older adult setting. Worse disease-free and overall survival outcomes are observed in the AYA setting, and the incidence of AYA cancers is increasing. Knowledge of an individual’s underlying cancer predisposition can influence their clinical care and may facilitate early tumour surveillance strategies and cascade testing of at-risk relatives. This information can further influence reproductive decision making. In this review we discuss the risk factors contributing to AYA breast cancer, such as heritable predisposition, environmental, and lifestyle factors. We also describe a number of risk models which incorporate genetic factors that aid clinicians in quantifying an individual’s lifetime risk of disease.

King Abdulaziz University Breast Cancer Mammogram Dataset (KAU-BCMD)

The current era is characterized by the rapidly increasing use of computer-aided diagnosis (CAD) systems in the medical field. These systems need a variety of datasets to help develop, evaluate, and compare their performances fairly. Physicians indicated that breast anatomy, especially dense ones, and the probability of breast cancer and tumor development, vary highly depending on race. Researchers reported that breast cancer risk factors are related to culture and society. Thus, there is a massive need for a local dataset representing breast cancer in our region to help develop and evaluate automatic breast cancer CAD systems. This paper presents a public mammogram dataset called King Abdulaziz University Breast Cancer Mammogram Dataset (KAU-BCMD) version 1. To our knowledge, KAU-BCMD is the first dataset in Saudi Arabia that deals with a large number of mammogram scans. The dataset was collected from the Sheikh Mohammed Hussein Al-Amoudi Center of Excellence in Breast Cancer at King Abdulaziz University. It contains 1416 cases. Each case has two views for both the right and left breasts, resulting in 5662 images based on the breast imaging reporting and data system. It also contains 205 ultrasound cases corresponding to a part of the mammogram cases, with 405 images as a total. The dataset was annotated and reviewed by three different radiologists. Our dataset is a promising dataset that contains different imaging modalities for breast cancer with different cancer grades for Saudi women.

Joanne Knight Breast Health Cohort at Siteman Cancer Center: A model last cohort

PurposeThe Joanne Knight Breast Health Cohort was established to link breast cancer risk factors, mammographic breast density, benign breast biopsies and associated tissue markers, and blood markers in a diverse population of women undergoing routine mammographic screening.MethodsWomen were recruited from November 2008 to April 2012. Baseline questionnaire risk factors, blood, and screening mammograms were collected from 12,153 women. Of these, 1,672 were excluded for prior history of any cancer (except non-melanoma skin) or diagnosis of breast cancer within 6 months of blood draw/registration for the study, for a total of 10,481 women. Follow-up is through linking to electronic health records, tumor registry and death register. Routine screening mammograms are collected every 1 to 2 years and incident benign breast biopsies and cancers are identified through record linkage to pathology and tumor registries. Formal fixed tissue samples are retrieved and stored for analysis. County-level measures of structural inequality were derived from publicly available resources.ResultsCohort Composition: median age at entry was 54.8 years and 26.7% are African American. Through 2020, 74 percent of participants have had a medical center visit within the past year and 80% within the past 2 years representing an average of 9.7 person years of follow-up from date of blood draw per participant. 9,997 women continuing in follow-up. Data collected at baseline include breast cancer risk factors, baseline plasma and white blood cells, mammograms prior to baseline, at baseline, and during follow-up. ConclusionThis cohort assembled and followed in a routine clinical screening and care setting that serves a diverse population of women in the St Louis region, now provides opportunities to integrate study of questionnaire measures, plasma and DNA markers, benign and malignant tissue markers, and breast image features into prospective evaluation for breast cancer etiology and outcomes.

Revisiting Candidacy: What Might It Offer Cancer Prevention?

The notion of candidacy emerged three decades ago through Davison and colleagues’ exploration of people’s understanding of the causes of coronary heart disease. Candidacy was a mechanism to estimate one’s own or others risk of disease informed by their lay epidemiology. It could predict who would develop illness or explain why someone succumbed to it. Candidacy’s predictive ability, however, was fallible, and it was from this perspective that the public’s reticence to adhere to prevention messages could be explained, as ultimately anybody could be ‘at-risk’. This work continues to resonate in health research, with over 700 citations of Davison’s Candidacy paper. Less explored however, is the candidacy framework in its entirety in other illness spheres, where prevention efforts could potentially impact health outcomes. This paper revisits the candidacy framework to reconsider it use within prevention. In doing so, candidacy within coronary heart disease, suicide prevention, diabetes, and cancer will be examined, and key components of candidacy and how people negotiate their candidacy within differing disease contexts will be uncovered. The applicability of candidacy to address modifiable breast cancer risk factors or cancer prevention more broadly will be considered, as will the implications for public health policy.

Evaluation of knowledge, awareness and attitudes towards breast cancer risk factors and early detection among females in Bangladesh: A hospital based cross-sectional study

Background Breast cancer (BCa) is a leading cause of mortality among women in Bangladesh. Many young women in Bangladesh have poor knowledge about breast cancer screening, including risk factors, warning signs/symptoms, diagnosis and early detection. We investigated awareness about breast cancer risk factors as a screening tool among women at the Sheikh Hasina Medical College (SHMC) of Tangail district in Bangladesh. Methods A cross sectional survey was conducted to collect data via a structured questionnaire from SHMC during the period of February to December 2019. A total of 1,007 participants (aged 33.47 (±12.37 years)) was considered for data analysis. Results Of the 1,007 women, about 50% were knowledgeable about the risk factors. Pain in the breast was identified as the most commonly warning sign/symptom of breast cancer. Only 32.2% of respondents knew at least one breast cancer screening method. The mean knowledge was scored 3.43 ± 2.25 out of a total possible score of 8. Awareness of BCa was associated with residence, family history of breast cancer, marital, literacy and socio-economic status (p <0.05). Only 14.7% of women who knew about BSE said they were conducting regular breast self-examination. Unmarried women (aOR: 2.971; 95% CI: 1.108–7.968) were more likely to have performed BSE compared to married women (p <0.05). Conclusion Although most participants were aware of breast cancer; knowledge about risk factors, warning signs/symptoms, early diagnosis and detection was relatively poor. Knowledge about performing BSE was particularly low. This highlights the importance of increasing awareness about breast cancer risk factors and early detection among young women in Bangladesh.

Combination of a 15-SNP Polygenic Risk Score and Classical Risk Factors for the Prediction of Breast Cancer Risk in Cypriot Women

The PRS combines multiplicatively the effects of common low-risk single nucleotide polymorphisms (SNPs) and has the potential to be used for the estimation of an individual’s risk for a trait or disease. PRS has been successfully implemented for the prediction of breast cancer risk. The combination of PRS with classical breast cancer risk factors provides a more comprehensive risk estimation and could, thus, improve risk stratification and personalized preventative strategies. In this study, we assessed the predictive performance of the combined effect of PRS15 with classical breast-cancer risk factors in Cypriot women using 1109 cases and 1177 controls from the MASTOS study. The PRS15 was significantly associated with an increased breast cancer risk in Cypriot women OR (95% CI) 1.66 (1.25–2.19). The integrated risk model obtained an AUC (95% CI) 0.70 (0.67–0.72) and had the ability to stratify women according to their disease status at the extreme deciles. These results provide evidence that the combination of PRS with classical risk factors may be used in the future for the stratification of Cypriot women based on their disease risk, and support its potential clinical utility for targeted preventative actions and population screening.