Risk Factors For Breast Cancer Research Articles

Alcohol consumption trajectories and risk of breast cancer among postmenopausal women: a Danish cohort study.

Alcohol consumption is a risk factor for breast cancer (BC), yet little is known about longitudinal alcohol consumption patterns and risk of BC. This study aimed to investigate whether trajectory profiles of alcohol consumption across adulthood were associated with risk of first primary malignant BC in postmenopausal women. At baseline, 28,720 pre-and postmenopausal women aged 50-65 years from the Danish Diet, Cancer and Health Cohort reported their average alcohol intake over the past 12 months and their average alcohol intake at the ages of 20, 30, 40, and 50 years. Alcohol consumption trajectories were estimated using latent class mixed models. BC cases were identified through record linkage to the Danish Cancer Registry. To examine associations between alcohol consumption trajectories and BC, we fitted a proportional hazard model adjusted for potential confounding factors using data from 24,543 postmenopausal women without missing covariate information. We identified 4 alcohol consumption trajectory profiles. During a median follow-up of 16.5 years, 1,591 cases of BC occurred. A mean alcohol consumption trajectory of > 10g/day was associated with higher risk of BC (HR: 1.65, 95%CI: 1.35-2.03) compared to a mean alcohol consumption trajectory of < 6g/day. We found no association between trajectory profiles characterized by lower alcohol intakes in early adulthood followed by increasing consumption of alcohol in adulthood compared to a consistently low intake of alcohol. Postmenopausal women drinking consistently high amounts of alcohol throughout adulthood had a higher risk of BC compared to women with a consistently low intake of alcohol.

Effectiveness of aerobic exercise intervention on cardiovascular disease risk in female breast cancer: a systematic review with meta-analyses

BackgroundCardiovascular disease (CVD) has become the leading cause of competitive mortality in female breast cancer (BC). Regular aerobic exercise (AE) has been widely accepted as an effective intervention to reduce cardiovascular risk in a variety of different clinical conditions. This study is aimed at evaluating the efficacy and safety of AE on cardiovascular risk factors in female BC and assessing the quality of the synthesized evidence.MethodsWe searched five English databases (Cochrane Library, PubMed, Embase, Scopus, and Web of Science) from inception to January 2023. Randomized controlled trials (RCTs) and cohort trials studying the effects of AE intervention on cardiovascular disease risk in female breast cancer were included. We used Stata 16 for data synthesis, Risk of Bias 2, and the Newcastle–Ottawa Scale for methodological quality evaluation and assessed the certainty of the synthesized evidence in the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.ResultsForty RCTs and 6 cohort trials involving 44,877 BC patients showed AE reduced the incidence of CVD events by 29.4% [risk ratio (RR) = 0.706, 95% confidence interval (CI) (0.659, 0.757), low certainty] and coronary artery disease events by 36% [RR = 0.640, 95% CI (0.561, 0.729), low certainty]. AE improved LVEF, and reduced weight and hip circumference. The subgroup analysis results showed that nonlinear AE increased VO2max by 5.354 ml·kg·min−1 [mean difference (MD) = 5.354, 95% CI (2.645, 8.062), very low certainty] and reduced fat mass by 4.256 kg [MD = 4.256, 95% CI (-3.839, -0.094), very low certainty]. While linear AE reduced low-density lipoprotein cholesterol (LDL-C) by 8.534 mg/dL [MD = -8.534, 95% CI (-15.511, -1.557), low certainty]. The sensitivity analysis results showed that each trial did not affect the impact index of the highly heterogeneous outcomes.ConclusionsOur study indicates that AE has a positive effect in reducing cardiovascular risk factors. The individualization principle of AE deserves more attention in the future. This will provide new ideas to reduce CVD events and improve the quality of life in female BC patients. However, further research on AE in female BC should take into account long-term and well-designed administration to draw definitive conclusions.

Alu–Mediated Duplication and Deletion of Exon 11 Are Frequent Mechanisms of PALB2 Inactivation, Predisposing Individuals to Hereditary Breast–Ovarian Cancer Syndrome

Background/Objective: Large genomic rearrangements of PALB2 gene, particularly deletions and duplications, have been linked to hereditary breast–ovarian cancer. Our research specifically focuses on delineating the intronic breakpoints associated with rearrangements of PALB2 exon 11, which is crucial for understanding the mechanisms underlying these genomic changes in patients with hereditary breast and ovarian syndrome. Methods: By using next-generation sequencing, we identified one duplication and three deletions of PALB2 exon 11, confirmed by Multiplex Ligation-Dependent Probe Amplification analysis. To assess the impact on transcription and potential splicing issues, reverse-transcription PCR was performed on patients’ RNA. For the detailed characterization of intronic breakpoints, the primer walking approach and long-range PCR were implemented, followed by Sanger sequencing. Results: Our analysis revealed a tandem duplication of 5134 base pairs (bp) mediated by AluY repeats located in introns 10 and 11, respectively. Moreover, identical deletions were identified in three unrelated patients, encompassing an approximate 8050 bp region mediated by AluSx elements. Both genomic alterations resulted in a truncated PALB2 protein due to the introduction of a premature stop codon. Conclusions: This study underscores the remarkable instability of intronic regions flanking exon 11 of PALB2 and identifies a previously unreported hotspot involving Alu repeats with very high sequence homology in introns 10 and 11 of the gene. Our findings suggest avenues for further research, such as investigating the prevalence of similar genomic rearrangements in larger cohorts and exploring functional studies to understand how these alterations contribute to hereditary breast cancer pathogenesis.

Age at first menstruation and clinical breast cancer screening utilization: insights from the 2021 Côte d'Ivoire demographic and health survey

BackgroundThere is a strong evidence showing that women who start menstruation early are at a greater risk of developing breast cancer. Recognizing that women will seek breast cancer screening when they have a high perceived risk, we hypothesized that women who experienced early menarche will be more likely to utilize clinical breast examination (CBE). Hence, we aimed to investigate the association between age at first menstruation and women’s utilization of CBE in Côte d'Ivoire.MethodsWe used data from the 2021 Côte d'Ivoire demographic and health survey. A sample of 14,685 women was used for the analysis. A descriptive analysis, as well as bivariate and multivariate logistic regression models were computed in STATA version 18. Adjusted odds ratio (AOR) and a 95% confidence interval was used to present the result.ResultsCBE utilization was 17.4%. Women who had their first menstruation before attaining 15 years were significantly less likely to utilize CBE services [AOR = 0.89; 95% CI 0.81–0.99]. A significantly higher utilization of CBE was found among those with primary [AOR = 1.48, 95% CI 1.29–1.70], secondary [AOR = 2.96, 95% CI 2.59–3.38], and higher education [AOR = 4.35, 95% CI 3.50–5.40] compared to those with no formal education. Increasing likelihood of CBE utilization was observed as age increased. Rural residence was associated with lower odds of CBE utilization (AOR = 0.84, 95% CI 0.74–0.95]. Increasing wealth status was associated with higher odds of CBE utilization with those in the richest households having the highest odds compared to women in the poorest household [AOR = 2.11, 95% CI 1.69–2.64].ConclusionUtilization of CBE is low among women of reproductive age in Côte d'Ivoire. We conclude that even though existing literature has established early age at first menstruation as a strong risk factor for breast cancer, CBE utilization is significantly low among those who had early menarche. Going forward, it is necessary for Côte d'Ivoire’s health Ministry to intensify breast cancer awareness in the country. Such awareness campaigns must emphasize age at menarche as a risk factor so as to motivate women with a history of early menstruation to utilize CBE.

Rare germline variants in cancer-relevant genes are associated with breast cancer risk in young women with high-risk family history.

It is incompletely understood why some women develop breast cancer 15-20years earlier than the majority of women. We hypothesize that women with early-onset breast cancer and high-risk family history without germline pathogenic variants in cancer-predisposing genes (CPGs, n = 83) have a higher load of germline high functional impact variants (gHFI) in cancer hallmark genes (n = 1508) compared to healthy controls. Germline whole exome sequencing data were analyzed from 5818 breast cancer cases from UKBiobank and from 94 young women with breast cancer without CPG pathogenic variants from the Yale Cancer Prevention Clinic, and compared to 149 controls from Yale GENERATIONS project and 56,917 controls from UKBiobank. Rare gHFI variants were compared between cases and controls using the burden test and the optimal unified SNP-set Kernel Association Test (SKAT-O). We assessed germline versus somatic origins of pathway level alterations in the TCGA and Yale data. In UKBiobank, higher gHFI variant load was seen in CPGs in cancer cases regardless of family history (p < 8.78 × 10-8), and in hallmark genes in cases with family history vs controls (p = 0.0093). Similarly, numerically higher rare gHFI burden was seen in hallmark genes in the Yale cohort vs controls, but this difference was not statistically significant. Pathway level alterations were dominated by somatic events. These results suggest that rare germline variants in cancer biology-related genes partly mediate the contribution of family history to cancer risk in individuals without germline alterations in high penetrance CPGs.

Plasma prolactin and postmenopausal breast cancer risk: a pooled analysis of four prospective cohort studies.

Prolactin, a hormone produced by the pituitary gland, regulates breast development and may contribute to breast cancer etiology. However, most epidemiologic studies of prolactin and breast cancer have been restricted to single, often small, study samples with limited exploration of effect modification. The Biomarkers in Breast Cancer Risk Prediction consortium includes 8,279 postmenopausal women sampled from four prospective cohort studies, of whom 3,441 were diagnosed with invasive breast cancer after enrollment. Prolactin concentrations were measured for all study participants on plasma samples collected when all women were postmenopausal and before any breast cancer diagnosis using ELISA assays. Pooled, unconditional logistic regression models, adjusted for confounders, estimated odd ratios (OR) for associations of prolactin and postmenopausal breast cancer risk overall and stratified by breast cancer risk factors. Higher plasma prolactin concentrations were positively associated with postmenopausal breast cancer risk (> 13.2 ng/mL vs. < 7.9 ng/mL, OR: 1.20, 95% CI: 1.06, 1.36; P-trend < 0.001). Although associations did not appear to vary by time since blood draw or most breast cancer risk factors, associations were primarily observed in current users of postmenopausal hormones at blood draw (> 13.2 ng/mL vs. < 7.9 ng/mL, current users, OR: 1.58, 95% CI: 1.27, 1.96, P-trend < 0.001; non-current users, OR: 1.08, 95% CI: 0.93, 1.27, P-trend = 0.11; P-heterogeneity = 0.06). Prolactin may be a risk factor for postmenopausal breast cancer, particularly in the context of postmenopausal hormone use. Investigations of prolactin interactions with other hormonal factors may further inform breast cancer etiology.

Simulated Galactic Cosmic Radiation Exposure-Induced Mammary Tumorigenesis in ApcMin/+ Mice Coincides with Activation of ERα-ERRα-SPP1 Signaling Axis

Background: Exposure to galactic cosmic radiation (GCR) is a breast cancer risk factor for female astronauts on deep-space missions. However, the specific signaling mechanisms driving GCR-induced breast cancer have not yet been determined. Methods: This study aimed to investigate the role of the estrogen-induced ERα-ERRα-SPP1 signaling axis in relation to mammary tumorigenesis in female ApcMin/+ mice exposed to simulated GCR (GCRsim) at 100–110 days post-exposure. Results: In GCRsim-exposed mice, we observed marked elevations in serum estradiol, increased ductal overgrowth, ERα activation, and upregulation of ERα target genes with pro-tumorigenic functions in mammary tissues that was coupled with a higher mammary tumorigenesis, relative to control. Additionally, the ERα target gene Esrra, which encodes ERRα, was also upregulated along with its oncogenic target gene Spp1, indicating the activation of the ERα-ERRα-SPP1 axis in mouse mammary tissues after GCRsim exposure. Using a human tissue microarray and human breast cancer gene expression analysis, we also highlighted the conserved nature of the ERα-ERRα-SPP1 signaling in human breast cancer development. Conclusions: We identified the ERα-ERRα-SPP1 signaling axis as a potential key mediator in GCR-induced breast cancer with conserved activation in human breast cancer. These findings suggest that targeting this pathway could serve as a potential target for therapeutic intervention to safeguard female astronauts during and after a prolonged outer space mission.

Longitudinal history of mammographic breast density and breast cancer risk by familial risk, menopausal status, and initial mammographic density level in a high risk cohort: a nested case–control study

BackgroundElevated mammographic density is associated with increased breast cancer risk. However, the contribution of longitudinal changes in mammographic density to breast cancer risk beyond initial mammographic density levels, considering familial breast cancer risk and menopausal status, remains uncertain but holds important clinical implications.MethodsIn a nested case–control study within the Sister Study (323 cases, 899 controls; 12,095 mammograms), a cohort enriched for family history of breast cancer, we examined case–control status in relation to the largest annual change in percent density and dense area using mammograms available spanning 5.4 years, on average, using multivariable logistic regression and to the rate of mammographic density change using linear mixed-effects models. We considered effect modification by: mammographic density level of the earlier mammogram, the extent of family history, Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation (BOADICEA) risk strata, and menopausal status.ResultsCases (diagnosed < 60 years) had greater initial percent density and dense area levels and a slower rate of decline in dense area than controls. Women with stable mammographic density (≤ 10% annual change) had an increased breast cancer risk as compared with women whose largest mammographic density change was > 10% annual decline (e.g., Odds Ratio (OR) 2.34, 95% Confidence Interval (CI) 1.63–3.37 for dense area). Increasing vs. decreasing dense area was also associated with elevated risk, especially in women with the highest dense area levels at the earlier mammogram (OR: 2.56, 95%CI 1.50–4.36). Although generally similar across menopausal and familial risk categories, the associations of MD change with risk appeared stronger in pre-menopausal and lower-risk women.ConclusionsWomen who maintain higher levels of mammographic density (i.e. do not decrease over time) or have increasing mammographic density over time have a higher risk of subsequent breast cancer than women with high mammographic density that decreases over time. These findings suggest potential for incorporating mammographic density trajectories in clinical risk assessment, and the importance of additional breast cancer monitoring in women not experiencing declines in mammographic density over time.

Comprehensive single-cell aging atlas of healthy mammary tissues reveals shared epigenomic and transcriptomic signatures of aging and cancer.

Aging is the greatest risk factor for breast cancer; however, how age-related cellular and molecular events impact cancer initiation is unknown. In this study, we investigated how aging rewires transcriptomic and epigenomic programs of mouse mammary glands at single-cell resolution, yielding a comprehensive resource for aging and cancer biology. Aged epithelial cells exhibit epigenetic and transcriptional changes in metabolic, pro-inflammatory and cancer-associated genes. Aged stromal cells downregulate fibroblast marker genes and upregulate markers of senescence and cancer-associated fibroblasts. Among immune cells, distinct T cell subsets (Gzmk+, memory CD4+, γδ) and M2-like macrophages expand with age. Spatial transcriptomics reveals co-localization of aged immune and epithelial cells in situ. Lastly, we found transcriptional signatures of aging mammary cells in human breast tumors, suggesting possible links between aging and cancer. Together, these data uncover that epithelial, immune and stromal cells shift in proportions and cell identity, potentially impacting cell plasticity, aged microenvironment and neoplasia risk.

Role of Proteins in Oncology: Advances in Cancer Diagnosis, Prognosis, and Targeted Therapy—A Narrative Review

Modern oncology increasingly relies on the role of proteins as key components in cancer diagnosis, prognosis, and targeted therapy. This review examines advancements in protein biomarkers across several cancer types, including breast cancer, lung cancer, ovarian cancer, and hepatocellular carcinoma. These biomarkers have proven critical for early detection, treatment response monitoring, and tailoring personalized therapeutic strategies. The article highlights the utility of targeted therapies, such as tyrosine kinase inhibitors and monoclonal antibodies, in improving treatment efficacy while minimizing systemic toxicity. Despite these advancements, challenges like tumor resistance, variability in protein expression, and diagnostic heterogeneity persist, complicating universal application. The review underscores future directions, including the integration of artificial intelligence, advanced protein analysis technologies, and the development of combination therapies to overcome these barriers and refine personalized cancer treatment.

Exploring bacterial key genes and therapeutic agents for breast cancer among the Ghanaian female population: Insights from In Silico analyses

Exploring bacterial key genes and therapeutic agents for breast cancer among the Ghanaian female population: Insights from In Silico analyses

Awareness of breast cancer and perceived barriers to breast screening methods: a community based cross-sectional study among women in Yemen

BackgroundIn Yemen, effective early detection and a comprehensive grasp of breast cancer symptoms and risk factors are vital in preventing its potentially deadly spread. However, challenges arise in combating breast cancer in Yemen due to the lack of patient registries, national strategies, and structured cancer treatment plans.ObjectiveThis research sought to evaluate the awareness levels of breast cancer and the perceived obstacles to breast cancer screening among adult Yemeni women.MethodsA community-based cross-sectional questionnaire study was conducted from September 2023 to January 2024 from two teaching and largest hospitals in the capital municipality, Sana’a, Yemen, where 533 women (≥ 18 years old) were conveniently selected in this study. Data were analyzed using SPSS software (version 23).. The Chi-square test was used to test associations. The factors associated with breast cancer awareness and barriers to breast cancer screening were analyzed separately, using multivariable logistic regression.ResultsThe study revealed that 88.6% of women were familiar with breast cancer, and 61.9% being knowledgeable about screening methods such as clinical breast examination (CBE) or mammography. The primary hindrance to screening (84.1%, n = 53) was the absence of symptoms or pain. The second most common reason for not undergoing screening was a lack of understanding about breast cancer and its treatment (61.9%, n = 39).ConclusionTo enhance breast cancer screening rates among Yemeni women consistently, targeted educational programs emphasizing the benefits of early detection and dispelling misconceptions and barriers related to the disease are essential.

Design and Synthesis of Various Aryl Amide Derivatives of Imidazo[1,5-a] Pyridine-1,2,4-Thiadiazoles: In Vitro Cytotoxicity Evaluation and In Silico Molecular Docking Studies.

A new series of various aryl amide derivatives of imidazo[1,5-a]pyridine-1,2,4-thiadiazoles (15a-j) were designed, synthesized, and evaluated for their cytotoxic profiles against four human cancer cell lines such as breast cancer (MCF-7), lung cancer (A549), colon cancer (Colo-205), and ovarian cancer (A2780), via the MTT assay, with etoposide as the standard known chemotherapeutic agent. Five compounds, 15a, 15b, 15c, 15f, and 15j, exhibited more potent cytotoxic effects than did etoposide. Among them, compound 15a exhibited potent cytotoxic effects against the MCF-7, A549, Colo-205, and A2780 cell lines, with IC50 values of 0.11±0.045µM, 0.94±0.047µM, 0.39±0.023µM, and 0.77±0.062µM, respectively. Through docking simulations of human topoisomerase IIβ, it is apparent that compounds 15a, 15b, 15c, and 15f manifested exceptional binding affinities and interaction profiles, surpassing the other compounds evaluated in this in silico study.

Pre-diagnosis blood DNA methylation profiling of twin pairs discordant for breast cancer points to the importance of environmental risk factors

BackgroundAssessment of breast cancer (BC) risk generally relies on mammography, family history, reproductive history, and genotyping of major mutations. However, assessing the impact of environmental factors, such as lifestyle, health-related behavior, or external exposures, is still challenging. DNA methylation (DNAm), capturing both genetic and environmental effects, presents a promising opportunity. Previous studies have identified associations and predicted the risk of BC using DNAm in blood; however, these studies did not distinguish between genetic and environmental contributions to these DNAm sites. In this study, associations between DNAm and BC are assessed using paired twin models, which control for shared genetic and environmental effects, allowing testing for associations between DNAm and non-shared environmental exposures and behavior.ResultsPre-diagnosis blood samples of 32 monozygotic (MZ) and 76 dizygotic (DZ) female twin pairs discordant for BC were collected at the mean age of 56.0 years, with the mean age at diagnosis 66.8 years and censoring 75.2 years. We identified 212 CpGs (p < 6.4*10–8) and 15 DMRs associated with BC risk across all pairs using paired Cox proportional hazard models. All but one of the BC risks associated with CpGs were hypomethylated, and 198/212 CpGs had their DNAm associated with BC risk independent of genetic effects. According to previous literature, at least five of the top CpGs were related to estrogen signaling. Following a comprehensive two-sample Mendelian randomization analysis, we found evidence supporting a dual causal impact of DNAm at cg20145695 (gene body of NXN, rs480351) with increased risk for estrogen receptor positive BC and decreased risk for estrogen receptor negative BC.ConclusionWhile causal effects of DNAm on BC risk are rare, most of the identified CpGs associated with the risk of BC appear to be independent of genetic effects. This suggests that DNAm could serve as a valuable biomarker for environmental risk factors for BC, and may offer potential benefits as a complementary tool to current risk assessment procedures.

Response to Carboplatin and Paclitaxel in the treatment of hereditary breast ovarian cancer syndrome (HBOC): a case report

The co-occurrence of primary breast cancer and primary ovarian cancer is an exceptional hereditary phenomenon and results from inherent mutations in critical genes like BRCA1/2, PALB2, TP53, CHEK1, and ATM. We present here a unique case of hereditary breast-ovarian cancer syndrome (HBOC) reported in Combined Military Hospital, Lahore, Pakistan. It was marked by pathogenic variants in RAD51D, PALB2, CHEK1, and TP53 genes. Remarkably, the patient exhibited an outstanding response to the chemotherapy agents, Carboplatin and Paclitaxel. This dynamic treatment not only led to nearly complete remission of high-grade ovarian serous cancer but also triggered regression in grade-2 invasive ductal breast cancer after just a few rounds of chemotherapy. Consequently, what started as palliative care evolved into a curative triumph. Keywords: Hereditary breast ovarian cancer, Breast cancer, Ovarian cancer, HBOC, BRCA, PALB2, Chemotherapy, Carboplatin, Paclitaxel.

Mammographic density in relation to breast cancer risk factors among Chinese women.

Background Increased mammographic density (MD) is a known breast cancer (BC) risk factor, but its influencing factors are unclear in Asian populations. This study examined the links between known BC risk factors and quantitatively measured MD in 7,351 Chinese women with non-malignant mammographic findings. Methods VolparaDensity software quantified volumetric MD measures: total breast (TBV), absolute dense (ADV), percent dense (PDV= ADV/TBV), and non-dense volumes (NDV= TBV-ADV). Multivariable linear regression models assessed associations between these MD metrics and BC risk factors. Results The mean age of the population was 50.1 (SD=8.3) years. The mean ADV, NDV, and PDV were 58.4 (SD=32.1), 382.8 (SD=202.0) cm³ and 14.8 (SD=7.1) %, respectively. PDV was inversely associated with age, weight, body mass index (BMI), parity, breastfeeding duration, and postmenopausal status, but positively linked to height and age at menopause. NDV showed opposite associations. ADV had similar associations to PDV, except for height, weight, and BMI, which differed for women with the lowest NDV. PDV associations with age at menarche, age at first birth, and breastfeeding duration varied by BMI and menopausal status. Conclusions MD may influence the relationship between reproductive factors and BC risk, depending on MD measure, menopausal status, and BMI. Impact This study examines how quantitative MD measures relate to known BC risk factors in an East Asian population, factoring in menopausal status and BMI. The results underscore the complex role of MD and confounding factors in BC risk, highlighting the need for tailored insights for future research and screening.

Anticancer activity of the synthetic kusunokinin analogues on human cancer cell lines

The series of racemic kusunokinin derivatives were synthesized and their cytotoxic activities and cell viability on cancer cells including breast cancer (MCF-7, MDA-MB468), colon cancer (HT-29), cholangiocarcinoma (KKU-M213) and ovarian cancer (A2780) cells were investigated. The results showed that compounds 6aa, 6da, and 6de exhibited growth inhibition against breast cancer (MDA-MB468), cholangiocarcinoma (KKU-M213), colon cancer (HT-29), and ovarian cancer (A2780) cells with IC50 values (μM) 13.77 ± 0.38, 7.94 ± 0.45, and 4.22 ± 0.13 (MDA-MB468); 4.21 ± 0.21, 0.97 ± 0.03, and 0.09 ± 0.02 (KKU-M213); 22.66 ± 0.23, and 15.62 ± 0.06 (HT-29); 13.11 ± 0.37, 11.51 ± 0.43, and 1.87 ± 0.01 (A2780); respectively. Interestingly, a positive control, doxorubicin, showed less cytotoxicity than 6da and 6de on cholangiocarcinoma KKU-M213 and ovarian cancer A2780 cells. Moreover, these three synthetic compounds also exhibited less toxicity than doxorubicin on the normal cells, MMNK-1, Vero and L-929. The binding possibility towards CSF1R, 6de (−11.59 kcal/mol) and trans-(−)-kusunokinin (−11.75 kcal/mol) were similar in both docking energies and docking poses. 6de interacted with Trp550 via π-π stacking in the similar manner with trans-(−)-kusunokinin and trans-(+)-kusunokinin.

BPE on contrast-enhanced mammography: relationship with breast density, age and menopausal status.

This retrospective study aimed to evaluate the relationship between BPE on CEM and breast density, age and menopausal status. Our analysis included all women eligible for CEM as a second-level examination in the diagnostic phase in a 12-month period. CEM were performed on a dedicated low-dose digital mammography unit after the injection of 1.5ml/kg body weight Iohexol 350 mgI/ml. Both breast composition and BPE were assessed independently by two breast radiologists according to the CEM supplement to the 2013 ACR BI-RADS Mammography. A two-stage ordered probit regression model was fitted to evaluate the relationship between BPE and the other factors considered. 49 patients were included (median age = 55years, 28.6% premenopausal and 71.4% postmenopausal). Breast composition was classified as ACR BI-RADS a in 4.1%, ACR BI-RADS b in 36.7%, ACR BI-RADS c in 46.9%, and ACR BI-RADS d in 12.2% of cases, by both Readers. A BPE 1 category was assigned in 53.1-55.1% of patients (by Reader 1 and 2, respectively), BPE 2 in 22.4%, BPE 3 in 18.4-12.2%, and BPE 4 in 6.1-10.2%. Higher breast density was strongly associated with higher levels of BPE, while BPE was not directly associated with age, both in fertile and postmenopausal patients. No significant differences were observed between the two Readers. Increased BPE is associated with a well-established breast cancer risk factor as high breast density, while it was not directly dependent on the other non-modifiable factors considered.

A Machine Learning Approach for Breast Cancer Risk Prediction in Digital Mammography

Breast cancer is among the most prevalent cancers in the female population globally. Therefore, screening campaigns as well as approaches to identify patients at risk are particularly important for the early detection of suspect lesions. This study aims to propose a workflow for the automatic classification of patients based on one of the most relevant risk factors in breast cancer, which is represented by breast density. The proposed classification methodology takes advantage of the features automatically extracted from mammographic images, as digital mammography represents the major screening tool in women. Textural features were extracted from the breast parenchyma through a radiomics approach, and they were used to train different machine learning algorithms and neural network models to classify the breast density according to the standard Breast Imaging Reporting and Data System (BI-RADS) guidelines. Both binary and multiclass tasks have been carried out and compared in terms of performance metrics. Preliminary results show interesting classification accuracy (93.55% for the binary task and 82.14% for the multiclass task), which are promising compared to the current literature. As the proposed workflow relies on straightforward and computationally efficient algorithms, it could serve as a basis for a fast-track protocol for the screening of mammograms to reduce the radiologists’ workload.

Gestational breast cancer: distinctive molecular and clinico-epidemiological features

Gestational breast cancer (GBC), defined as breast cancer (BC) diagnosed during pregnancy or the first-year post-partum, accounts for 6–15% of BC cases in women aged 20–44 years. GBC has worse prognosis than non-GBC, but reasons behind are not clear. The GEICAM/2012–03 Study (Molecular Characterization of Gestational Breast Cancer) is a multicenter prospective/retrospective observational registry of patients diagnosed with GBC. From November 2014 to June 2015 seventy patients diagnosed with GBC were included in the study, 30 diagnosed during pregnancy and 40 after delivery. Our current study was aimed to explore differences in epidemiological, clinico-pathological and gene expression features of GBC tumors, from the GEICAM/2012–03 Study, compared to non-GBC tumors from patients of similar age (< 43 years) from six different GEICAM studies, used as non- GBC control population. As per the main objective, the study found multiple differences showing GBC tumors as a different biological entity. GBC showed a more aggressive biology, with higher Ki67 levels, higher incidence of breast and/or ovarian cancer family history, and germline deleterious BRCA1/2 mutations, and are enriched in basal-like intrinsic subtype. GBC patients showed a lower number of tumor infiltrating lymphocytes, while specific genetic signatures highlight differences in GBC´s distinctive transcriptome. Our study shows that GBC is potentially a clinically and molecularly different entity, with specific epidemiological, clinical, and histological features, as well as a distinctive altered immune state and genetic signature. Nevertheless, further studies are needed to better understand the biology of GBC and to identify new targets against which develop new, more effective, targeted therapies.