Breast Cancer and Lifestyle Factors: Umbrella Review.

Lifestyle factors play a major role in the risk of breast cancer. This review aimed to examine the size of the effect of select lifestyle factors on risk for breast cancer and assess the quality of existing evidence. The authors performed an umbrella review of systematic reviews. The authors found an increased risk for breast cancer associated with obesity, alcohol intake, and smoking and a decreased risk due to physical activity. The evidence for sleep disruption and duration indicates risk for breast cancer, but it is limited in size, statistical significance, and quality of evidence.

Breast cancer risk factors based on reproductive and nonreproductive profiling of Pakistani women: A hospital based case control study.

Breast cancer (BC) is a global public health problem attributed to varying risk factors. The designing of a targeted screening program focused on at-risk women can be cost-effective in reducing its burden. A hospital based case control study was conducted on 138 cases of breast cancer and 169 healthy controls to investigate the reproductive and non-reproductive risk factors for breast cancer in Pakistani women. The odds ratios (ORs) and 95% confidence intervals (CIs) were computed with unconditional logistic regression. Almost all i.e. 97.83% of cases were married (OR=5.03),70.29% were illiterate (OR=1.88), 73.19% were aged >35 years (OR=0.632) and 81.16% belonged to the poor class(OR=1.81). Early age at menarche (OR, 2.55; 95% CI 1.50-4.31, P=0.0001), hormone replacement therapy (OR=2.057, 95% CI 1.283-3.295, P= 0.002) early pregnancy (OR,2.23, 95% CI 1.29-3.88, P=0.004), history of miscarriage (OR, 2.11, 95% CI 1.32-3.39,P=0.002) & oral contraceptive use (OR, 2.76, 95% CI 1.54-4.92, P= 0.006) were significantly associated with BC. The study highlights the dire need for effective public health programs for high-risk women to address this highly fatal disease.

Le cancer du sein (BC) est un problème de santé publique mondial attribué à divers facteurs de risque. La conception d'un programme de dépistage ciblé axé sur les femmes à risque peut s'avérer rentable pour réduire son fardeau. Une étude cas-témoins en milieu hospitalier a été menée sur 138 cas de cancer du sein et 169 témoins sains pour étudier les facteurs de risque reproductifs et non reproductifs du cancer du sein chez les femmes pakistanaises. Les rapports de cotes (OR) et les intervalles de confiance (IC) à 95 % ont été calculés par régression logistique inconditionnelle. La quasi-totalité soit 97,83% des cas étaient mariés (OR=5,03), 70,29% étaient analphabètes (OR=1,88), 73,19% étaient âgés de >35 ans (OR=0,632) et 81,16% appartenaient à la classe pauvre (OR=1,81). . Âge précoce aux premières règles (OR = 2,55 ; IC à 95 % 1,50-4,31, P = 0,0001), traitement hormonal substitutif (OR = 2,057, IC à 95 % 1,283-3,295, P = 0,002) grossesse précoce (OR , 2,23, IC à 95 % 1,29-3,88, P=0,004), les antécédents de fausse couche (OR, 2,11, IC à 95 % 1,32-3,39, P=0,002) et l'utilisation de contraceptifs oraux (OR, 2,76, IC à 95 % 1,54-4,92, P= 0,006) étaient significativement associé à la Colombie-Britannique. L'étude souligne le besoin urgent de programmes de santé publique efficaces destinés aux femmes à haut risque afin de lutter contre cette maladie hautement mortelle.

Dietary pattern and other factors of breast cancer among women: a case control study in Northwest Ethiopia.

INTRODUCTION: Breast cancer is presently the most commonly diagnosed cancer in women, and it stands as the leading cause of cancer-related deaths worldwide. Notably, breast cancer rates have seen a significant increase in sub-Saharan African countries, including Ethiopia. Several risk factors contribute to breast cancer, some of which can be modified, while others are inherent. Promoting a healthier diet is strongly encouraged as a preventive measure against breast cancer. However, it's noteworthy that no previous research has investigated the connection between dietary patterns and the risk of breast cancer among Ethiopian women. Therefore, the primary objective of the current study is to examine the relationship between dietary patterns, socioeconomic and behavior factors associated with breast cancer in Ethiopian women. METHODS: A case-control study was conducted at an institution in Bahir Dar, Northwest Ethiopia, involving 260 women, comprising 86 cases and 174 controls. We administered a standardized and validated questionnaire to assess a range of sociodemographic, reproductive, clinical, lifestyle, and dietary characteristics through face-to-face interviews. To analyze the differences between the cases and controls, we employed the Chi-square test. Furthermore, we assessed the relationships between these variables using binary multivariate logistic regression. To measure the association between variables, we utilized odds ratios with 95% confidence intervals. RESULTS: The results of the multivariate analysis indicated that participants in the younger age group had significantly lower odds of developing breast cancer (AOR = 0.05; 95% CI: 0.00-0.91) compared to those in the older age group. Additionally, women who breastfed their children for shorter durations were 3.66 times more likely to develop breast cancer (AOR = 3.66; 95% CI: 2.78-6.89) than those who breastfed for longer periods. Furthermore, women with sedentary lifestyles faced a significantly higher risk of breast cancer, with odds 10.53 times greater (AOR = 10.53; 95% CI: 5.21-21.36) than their counterparts who engaged in moderate or highly active lifestyles. Lastly, participants who had previously undergone chest therapy were 6.43 times more likely to develop breast cancer (AOR = 6.43; 95% CI: 3.20-13.90) compared to those who had not. CONCLUSIONS: Breast cancer prevention interventions, including breastfeeding counseling and increased physical activity should be recognized as a central strategy for lowering breast cancer risk. Furthermore, healthcare providers should aim to minimize exposure to chest radiation therapy.

Cumulative environmental quality is associated with breast cancer incidence differentially by summary stage and urbanicity.

Individual environmental contaminants have been associated with breast cancer; however, evaluations of multiple exposures simultaneously are limited. Herein, we evaluated associations between breast cancer summary stages and the Environmental Quality Index (EQI), which includes a range of environmental factors across five domains. The EQI (2000-2005) was linked to county-level age-standardized incidence rates (SIRs) obtained from the North Carolina Central Cancer Registry (2010-2014). Incidence rates and SIRs of total, in situ, localized, regional, and distant breast cancers were evaluated stratified by rural-urban status. In counties with poor environmental quality compared to those with good environmental quality, total breast cancer incidence was higher by 10.82 cases per 100,000 persons (95% CI 2.04, 19.60, p = 0.02). This association was most pronounced for localized breast cancer (ß = 5.59, 95% CI 0.59, 10.58, p = 0.03). Higher incidence of early-stage disease (carcinoma in situ ß = 5.25, 95% CI 2.34, 8.16, p = 0.00 and localized breast cancer ß = 6.98, 95% CI 2.24, 11.73, p = 0.00) and total breast cancer (ß = 11.44, 95% CI 3.01, 19.87, p = 0.01) occurred in counties with poor land quality, especially urban counties. Our analyses indicate significant associations between environmental quality and breast cancer incidence, which differ by breast cancer stage and urbanicity, identifying a critical need to assess cumulative environmental exposures in the context of cancer stage.

[Nutrition in breast cancer genesis]. / El papel de la nutrición en la génesis del cáncer de mama.

Introduction: Breast cancer is the most prevalent tumor in women, ranking first in incidence and mortality in many countries. Although the causes of breast cancer are complex and multifactorial, nutritional factors and those related to nutritional status play an important role in the development of the disease. In this way, factors that increase breast cancer risk have been identified, such as weight gain, the amount of adipose tissue, waist circumference, alcohol consumption or the consumption of red meat and processed meat, while other factors have been identified that reduce the risk, such as eating fruits and vegetables. Nutritional factors or factors that depend on the state of nutrition are modifiable and preventable, so they must be considered when designing effective prevention programs.

Introducción: El cáncer de mama es el tumor más prevalente en las mujeres y ocupa el primer lugar en incidencia y en mortalidad en muchos países. Si bien las causas del cáncer de mama son complejas y multifactoriales, los factores nutricionales y aquellos relacionados con el estado nutricional juegan un papel importante en el desarrollo de la enfermedad. De esta forma, se han identificado algunos factores que aumentan su riesgo, como el aumento de peso, la cantidad de tejido adiposo, la circunferencia de cintura, el consumo de alcohol, etc., o bien, que lo reducen, como el consumo de frutas y verduras. Los factores nutricionales o que dependen del estado de nutrición son modificables y prevenibles, por lo que deben tenerse en cuenta al diseñar programas de prevención eficaces.

Dosimetric Comparison of Postmastectomy Radiotherapy Plans for Synchronous Bilateral Breast Cancer, Including Regional Lymph Node Irradiation.

BACKGROUND: To investigate the optimal radiotherapy plans for synchronous bilateral breast cancer (SBBC) patients receiving postmastectomy radiotherapy (PMRT), including regional lymph node irradiation (RNI). METHODS: For 10 SBBC patients who underwent bilateral mastectomy and received bilateral PMRT with RNI, 3 integrally optimized plans with a single isocenter were designed for each patient in this retrospective study: intensity-modulated radiation therapy (IMRT) with 9 fixed beams (9F-IMRT), volumetric-modulated arc therapy (VMAT) with 2 pairs of half arcs (2F-VMAT), VMAT with 2 pairs of outer tangential arcs and 1 pair of 200-degree arcs (3F-VMAT). The paired t-test (in the case of normal variables) and Friedman's test (in the case of nonnormal variables) were applied to compare the planning target volumes (PTVs) and organs at risk (OARs) values of the 3 techniques. RESULTS: The 3 techniques provided adequate target dose coverage and comparable results for PTVs. For OARs, 3F-VMAT yielded the lowest mean or median values of the left lung (15.02 ± 1.57 Gy) and right lung (14.91 ± 1.14 Gy), heart (6.19 (1.96) Gy), coronary artery (15.96 ± 5.76 Gy) and liver (8.10 ± 2.70 Gy) which were significantly different from those of 9F-IMRT and 2F-VMAT. The percentages of volume at various doses (V5, V10, V20, and V30) of 3F-VMAT plans were also lower than or comparable with those of 9F-IMRT and 2F-VMAT. The monitor units (MUs) of 3F-VMAT were 31% higher than those of 9F-IMRT and comparable with those of 2F-VMAT; however, there were time savings and halved beam-on times (BOTs) compared to 9F-IMRT. CONCLUSIONS: The 3F-VMAT plan yielded comparable target coverage compared with 9F-IMRT and 2F-VMAT, was superior in dose sparing of normal tissues and enabled shorter BOTs, improving treatment efficiency. In our research, 3F-VMAT was the optimal radiotherapy technique for SBBC patients receiving PMRT including RNI.

Association between Gut Microbiota and Breast Cancer: Diet as a Potential Modulating Factor.

Breast cancer (BCa) has many well-known risk factors, including age, genetics, lifestyle, and diet; however, the influence of the gut microbiome on BCa remains an emerging area of investigation. This study explores the connection between the gut microbiome, dietary habits, and BCa risk. We enrolled newly diagnosed BCa patients and age-matched cancer-free controls in a case-control study. Comprehensive patient data was collected, including dietary habits assessed through the National Cancer Institute Diet History Questionnaire (DHQ). 16S rRNA amplicon sequencing was used to analyze gut microbiome composition and assess alpha and beta diversity. Microbiome analysis revealed differences in the gut microbiome composition between cases and controls, with reduced microbial diversity in BCa patients. The abundance of three specific microbial genera-Acidaminococus, Tyzzerella, and Hungatella-was enriched in the fecal samples taken from BCa patients. These genera were associated with distinct dietary patterns, revealing significant associations between the presence of these genera in the microbiome and specific HEI2015 components, such as vegetables and dairy for Hungatella, and whole fruits for Acidaminococus. Demographic characteristics were well-balanced between groups, with a significantly higher body mass index and lower physical activity observed in cases, underscoring the role of weight management in BCa risk. Associations between significant microbial genera identified from BCa cases and dietary intakes were identified, which highlights the potential of the gut microbiome as a source of biomarkers for BCa risk assessment. This study calls attention to the complex interplay between the gut microbiome, lifestyle factors including diet, and BCa risk.

The Clinical Relevance of the NATALEE Study: Application of the NATALEE Criteria to a Real-World Cohort from Two Large German Breast Cancer Centers.

The NATALEE study showed a significant benefit in invasive disease-free survival (iDFS) for patients with HR+/HER2- early breast cancer (eBC) at intermediate and high risk of recurrence who were treated with the CDK4/6 inhibitor Ribociclib in combination with endocrine therapy (ET). This retrospective study aims to apply the NATALEE inclusion criteria to a representative real-world cohort to estimate the proportion of HR+/HER2- breast cancer patients eligible for adjuvant Ribociclib therapy. Patients who underwent full surgical treatment for eBC between January 2018 and December 2020 at two large German university breast cancer centers (University of Ulm, University of Tuebingen) were included. Descriptive statistics were used to characterize the patient population eligible for Ribociclib treatment based on the NATALEE study's inclusion criteria. Out of 2384 enrolled patients, 1738 had HR+/HER2- eBC, of whom 43% (747/1738) met the NATALEE inclusion criteria. Of note, these patients were older, received less chemotherapy and presented with less advanced tumor stages compared to the NATALEE study cohort. Additionally, compared to the NATALEE study cohort, fewer patients had lymph node involvement (72.4% vs. 88.7%). Our analysis suggests that approximately 43% of all HR+/HER2- breast cancer patients will qualify for Ribociclib treatment. Given the numerous treatment options for patients with HR+/HER2- eBC, as well as the differences between the NATALEE cohort and patients in the real-world clinical setting, future analyses will be needed to determine which patients would benefit most from adjuvant CDK4/6 inhibitor treatment.

Reverse Onco-Cardiology: What Is the Evidence for Breast Cancer? A Systematic Review of the Literature.

Breast cancer and cardiovascular diseases (CVD) represent significant global health challenges, with CVD being the leading cause of mortality and breast cancer, showing a complex pattern of incidence and mortality. We explore the intricate interplay between these two seemingly distinct medical conditions, shedding light on their shared risk factors and potential pathophysiological connections. A specific connection between hypertension (HTN), atrial fibrillation (AF), myocardial infarction (MI), and breast cancer was evaluated. HTN is explored in detail, emphasizing the role of aging, menopause, insulin resistance, and obesity as common factors linking HTN and breast cancer. Moreover, an attempt is made to identify the potential impact of antihypertensive medications and highlight the increased risk of breast cancer among those women, with a focus on potential mechanisms. A summary of key findings underscores the need for a multisystem approach to understanding the relationship between CVD and breast cancer is also explored with a highlight for all the gaps in current research, such as the lack of clinical observational data on MI and breast cancer in humans and the need for studies specifically designed for breast cancer. This paper concludes that there should be a focus on potential clinical applications of further investigation in this field, including personalized prevention and screening strategies for women at risk. Overall, the authors attempt to provide a comprehensive overview of the intricate connections between breast cancer and cardiovascular diseases, emphasizing the importance of further research in this evolving field of cardio-oncology.

Evaluation of tumor-infiltrating lymphocytes and mammographic density as predictors of response to neoadjuvant systemic therapy in breast cancer.

BACKGROUND: Response rates vary among breast cancer patients treated with neoadjuvant systemic therapy (NAST). Thus, there is a need for reliable treatment predictors. Evidence suggests tumor-infiltrating lymphocytes (TILs) predict NAST response. Still, TILs are seldom used clinically as a treatment determinant. Mammographic density (MD) is another potential marker for NAST benefit and its relationship with TILs is unknown. Our aims were to investigate TILs and MD as predictors of NAST response and to study the unexplored relationship between TILs and MD. MATERIAL AND METHODS: We studied 315 invasive breast carcinomas treated with NAST between 2013 and 2020. Clinicopathological data were retrieved from medical records. The endpoint was defined as pathological complete response (pCR) in the breast. TILs were evaluated in pre-treatment core biopsies and categorized as high (≥10%) or low (<10%). MD was scored (a-d) according to the breast imaging reporting and data system (BI-RADS) fifth edition. Binary logistic regression and Spearman's test of correlation were performed using SPSS. RESULTS: Out of 315 carcinomas, 136 achieved pCR. 94 carcinomas had high TILs and 215 had low TILs. Six carcinomas had no available TIL data. The number of carcinomas in each BI-RADS category were 37, 122, 112, and 44 for a, b, c, and d, respectively. High TILs were independently associated with pCR (OR: 2.95; 95% CI: 1.59-5.46) compared to low TILs. In the univariable analysis, MD (BI-RADS d vs. a) showed a tendency of higher likelihood for pCR (OR: 2.43; 95% CI: 0.99-5.98). However, the association was non-significant, which is consistent with the result of the multivariable analysis (OR: 2.51; 95% CI: 0.78-8.04). We found no correlation between TILs and MD (0.02; p = .80). CONCLUSION: TILs significantly predicted NAST response. We could not define MD as a significant predictor of NAST response. These findings should be further replicated.

Common myths and misconceptions about breast cancer causation among Palestinian women: a national cross-sectional study.

BACKGROUND: The discussion about breast cancer (BC) causation continues to be surrounded by a number of myths and misbeliefs. If efforts are misdirected towards reducing risk from false mythical causes, individuals might be less likely to consider and adopt risk-reducing behaviors for evidence-based BC causes. This national study aimed to assess the awareness of BC causation myths and misbeliefs among Palestinian women, and examine the factors associated with having good awareness. METHODS: This national cross-sectional study recruited adult women from government hospitals, primary healthcare centers, and public spaces in 11 governorates in Palestine. A modified version of the Cancer Awareness Measure-Mythical Causes Scale was used to collect data. The level of awareness of BC causation myths was determined based on the number of myths recognized to be incorrect: poor (0-5), fair (6-10), or good (11-15). RESULTS: A total of 5,257 questionnaires were included. Only 269 participants (5.1%) demonstrated good awareness (i.e., recognizing more than 10 out of 15 BC mythical causes). There were no notable differences in displaying good awareness between the main areas of Palestine, the Gaza Strip and the West Bank and Jerusalem (5.1% vs. 5.1%). Having chronic disease as well as visiting hospitals and primary healthcare centers were associated with a decrease in the likelihood of displaying good awareness. Myths related to food were less frequently recognized as incorrect than food-unrelated myths. 'Eating burnt food' was the most recognized food-related myth (n = 1414, 26.9%), while 'eating food containing additives' was the least recognized (n = 599, 11.4%). 'Having a physical trauma' was the most recognized food-unrelated myth (n = 2795, 53.2%), whereas the least recognized was 'wearing tight bra' (n = 1018, 19.4%). CONCLUSIONS: A very small proportion of Palestinian women could recognize 10 or more myths around BC causation. There is a substantial need to include clear information about BC causation in future educational interventions besides focusing on BC screening, signs and symptoms, and risk factors.

Lipidome of mammographic breast density in premenopausal women.

BACKGROUND: High mammographic breast density (MBD) is a strong risk factor for breast cancer development, but the biological mechanisms underlying MBD are unclear. Lipids play important roles in cell differentiation, and perturbations in lipid metabolism are implicated in cancer development. Nevertheless, no study has applied untargeted lipidomics to profile the lipidome of MBD. Through this study, our goal is to characterize the lipidome of MBD in premenopausal women. METHODS: Premenopausal women were recruited during their annual screening mammogram at the Washington University School of Medicine in St. Louis, MO. Untargeted lipidomic profiling for 982 lipid species was performed at Metabolon (Durham, NC®), and volumetric measures of MBD (volumetric percent density (VPD), dense volume (DV), and non-dense volume (NDV)) was assessed using Volpara 1.5 (Volpara Health®). We performed multivariable linear regression models to investigate the associations of lipid species with MBD and calculated the covariate-adjusted least square mean of MBD by quartiles of lipid species. MBD measures were log10 transformed, and lipid species were standardized. Linear coefficients of MBD were back-transformed and considered significant if the Bonferroni corrected p-value was < 0.05. RESULTS: Of the 705 premenopausal women, 72% were non-Hispanic white, and 23% were non-Hispanic black. Mean age, and BMI were 46 years and 30 kg/m2, respectively. Fifty-six lipid species were significantly associated with VPD (52 inversely and 4 positively). The lipid species with positive associations were phosphatidylcholine (PC)(18:1/18:1), lysophosphatidylcholine (LPC)(18:1), lactosylceramide (LCER)(14:0), and phosphatidylinositol (PI)(18:1/18:1). VPD increased across quartiles of PI(18:1/18:1): (Q1 = 7.5%, Q2 = 7.7%, Q3 = 8.4%, Q4 = 9.4%, Bonferroni p-trend = 0.02). The lipid species that were inversely associated with VPD were mostly from the triacylglycerol (N = 43) and diacylglycerol (N = 7) sub-pathways. Lipid species explained some of the variation in VPD. The inclusion of lipid species increased the adjusted R2 from 0.45, for a model that includes known determinants of VPD, to 0.59. CONCLUSIONS: We report novel lipid species that are associated with MBD in premenopausal women. Studies are needed to validate our results and the translational potential.

Understanding the role of environmental and socioeconomic factors in the geographic variation of breast cancer risk in the US-wide Sister Study.

OBJECTIVE: To describe the geographic pattern of breast cancer incidence in a nationwide prospective cohort and investigate whether environmental exposures and/or neighborhood socioeconomic status explain observed geographic disparities. METHODS: Using accelerated failure time models with a spatial random effect term, we mapped the health region-level association between residential location and breast cancer incidence for 44,707 participants in the Sister Study after controlling for established individual-level breast cancer risk factors. We performed a variable selection process to select environmental exposures [i.e., ambient nitrogen dioxide (NO2) and fine particulate matter (PM2.5), PM2.5 chemical composition, outdoor light at night (LAN), ambient noise, ultraviolet radiation, and greenspace] and neighborhood-level factors [i.e., population density and area deprivation index (ADI)] that predicted breast cancer incidence and quantified the spatial variation explained by the selected factors. We also considered whether the geographic pattern and predictors were similar when restricting to estrogen receptor-positive (ER+) tumors. RESULTS: We observed a spatial patterning in the incidence of overall breast cancer (Moran's I = 16.7, p < 0.05) and ER+ breast cancer (Moran's I = 13.2, p < 0.05), with a lower risk observed in the South and Southeast and a greater risk in the Northwest and certain areas of the Midwest and Northeast. NO2, LAN, and ADI explained 21.4% of the spatial variation in overall breast cancer incidence whereas NO2, PM2.5 chemical composition, LAN, greenspace, and ADI together explained 63.3% of the spatial variation in ER+ breast cancer incidence. CONCLUSIONS: Our findings provide additional evidence for a role of environmental exposures in breast cancer incidence and suggest that geographic-based risk factors may vary according to breast cancer subtype. Our findings support the need for additional research to quantify the relative contributions of geographic-based risk factors for breast cancer.

Dietary advanced glycation end products are associated with an increased risk of breast cancer in Iranian adults.

BACKGROUND: Dietary advanced glycation end products (AGEs) can play an important role in increasing inflammatory factors and oxidative stress as risk factors for cancers. In the present study, we aimed to assess the relationship between dietary AGEs and the risk of breast cancer (BC) in Iranian adult women. METHODS: This hospital-based case-control study includes 401 participants aged ≥ 30 years old. The cases group consisted of 134 women diagnosed with histologically confirmed BC. The control group included 267 women enrolled randomly from patients admitted to the same hospitals. Dietary intake information was determined using a validated food frequency questionnaire, and dietary AGEs intake was computed for all participants. Logistic regression models, adjusted for potential confounders, were used to determine the odds ratios (OR) and 95% confidence interval (CI) of BC across tertiles of dietary AGEs. RESULTS: The mean ± SD age and body mass index of the study population were 47.92 ± 10.33 years and 29.43 ± 5.51 kg/m2, respectively. The median (interquartile) of dietary AGEs in all individuals was 9251(7450, 11,818) kU/day. After adjusting for age, first pregnancy age, and energy intake, participants in the highest tertile of dietary AGEs intakes had higher odds of BC compared to those in the lowest tertile of dietary AGEs (OR:2.29;95%CI:1.19-4.39, Ptrend:0.012). Additionally, in the multivariable model, after adjusting for age, age at first pregnancy, energy, menopausal status, family history of cancer, anti-inflammatory drug use, Vitamin D supplementation, physical activity, body mass index, number of childbirths, and history of abortion, breastfeeding, and oral contraceptive pills use, the odds of BC were increased across tertiles of dietary AGEs intake (OR: 2.33; 95%CI: 1.18-4.60, Ptrend: 0.017). CONCLUSION: The present findings suggest that a diet with high AGEs is associated with a higher likelihood of BC in adult women.

Trajectories of body mass index in adulthood and risk of subtypes of postmenopausal breast cancer.

BACKGROUND: Body fatness is a dynamic exposure throughout life. To provide more insight into the association between body mass index (BMI) and postmenopausal breast cancer, we aimed to examine the age at onset, duration, intensity, and trajectories of body fatness in adulthood in relation to risk of breast cancer subtypes. METHODS: Based on self-reported anthropometry in the prospective Norwegian Women and Cancer Study, we calculated the age at onset, duration, and intensity of overweight and obesity using linear mixed-effects models. BMI trajectories in adulthood were modeled using group-based trajectory modeling. We used Cox proportional hazards models to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for the associations between BMI exposures and breast cancer subtypes in 148,866 postmenopausal women. RESULTS: A total of 7223 incident invasive postmenopausal breast cancer cases occurred during follow-up. Increased overweight duration and age at the onset of overweight or obesity were associated with luminal A-like breast cancer. Significant heterogeneity was observed in the association between age at overweight and overweight duration and the intrinsic-like subtypes (pheterogeneity 0.03). Compared with women who remained at normal weight throughout adulthood, women with a descending BMI trajectory had a reduced risk of luminal A-like breast cancer (HR 0.54, 95% CI 0.33-0.90), whereas women with ascending BMI trajectories were at increased risk (HR 1.09; 95% CI 1.01-1.17 for "Normal-overweight"; HR 1.20; 95% CI 1.07-1.33 for "Normal-obesity"). Overweight duration and weighted cumulative years of overweight and obesity were inversely associated with luminal B-like breast cancer. CONCLUSIONS: In this exploratory analysis, decreasing body fatness from obesity in adulthood was inversely associated with overall, hormone receptor-positive and luminal A-like breast cancer in postmenopausal women. This study highlights the potential health benefits of reducing weight in adulthood and the health risks associated with increasing weight throughout adult life. Moreover, our data provide evidence of intrinsic-like tumor heterogeneity with regard to age at onset and duration of overweight.

Exploring Breast Cancer Systemic Drug Therapy Patterns in Real-World Data.

PURPOSE: To explore medications and their administration patterns in real-world patients with breast cancer. METHODS: A retrospective study was performed using TriNetX, a federated network of deidentified, Health Insurance Portability and Accountability Act-compliant data from 21 health care organizations across North America. Patients diagnosed with breast cancer between January 1, 2013, and May 31, 2022, were included. We investigated a rule-based and unsupervised learning algorithm to extract medications and their administration patterns. To group similar administration patterns, we used three features in k-means clustering: total number of administrations, median number of days between administrations, and standard deviation of the days between administrations. We explored the first three lines of therapy for patients classified into six groups on the basis of their stage at diagnosis (early as stages I-III v late as stage IV) and the sensitivity of the tumor's receptors to targeted therapies: hormone receptor-positive/human epidermal growth factor 2-negative (HR+/ERBB2-), ERBB2-positive (ERBB2+/HR±), or triple-negative (TN; HR-/ERBB2-). To add credence to the derived regimens, we compared them to the National Comprehensive Cancer Network (NCCN): Breast Cancer (version 2.2023) recommendations. RESULTS: In early-stage HR+/ERBB2- and TN groups, the most common regimens were (1) cyclophosphamide and docetaxel, administered once every 3 weeks for three to six cycles and (2) cyclophosphamide and doxorubicin, administered once every 2 weeks for four cycles, followed by paclitaxel administered once every week for 12 cycles. In the early-stage ERBB2+/HR± group, most patients were administered carboplatin and docetaxel with or without pertuzumab and with trastuzumab (for six or more cycles). Medications most commonly administered in our data set (7,798 patients) agreed with recommendations from the NCCN in terms of medications (regimens), number of administrations (cycles), and days between administrations (cycle length). CONCLUSION: Although there is a general agreement with the NCCN Guidelines, real-world medication data exhibit variability in the medications and their administration patterns.

[Association of Body Mass Index and Weight Gain With Obesity-Related Breast Cancer Risk Biomarkers in Adult Chinese Women].

Objective: To investigate the associatiojn of body mass index (BMI) at different stages of life and weight gain in adulthood with obesity-related breast cancer risk biomarkers and to provide evidence for formulating policies concerning the prevention and control of breast cancer. Methods: A cross-sectional study was designed based on the follow-up cohort of southwest China community-based breast cancer screening of women. Using sequential sampling, eligible participants were enrolled from the cohort as the subjects of the study. Information on the basic risk factors was collected and the height, weight, and plasma biomarker levels were measured. Multiple linear regression model was applied to analyze the associations of early adulthood BMI (defined as the BMI of the participant at age 20), adulthood BMI (defined as the BMI measured at the time of enrollment), and weight gain in adulthood with the biomarkers. The concentrations of the biomarkers were incorporated in the model after log transformation. Results: The average age of the 442 participants was 49 (45, 54) years old, the average early adulthood BMI and adulthood BMI were 21.47 (19.56, 23.11) and 24.10 (22.59, 25.97) kg/m 2, respectively, and the average weight gain in adulthood was 6.60 (2.00, 11.00) kg. Adulthood BMI was negatively associated with adiponectin level ( ß=-0.026, 95% CI: -0.045--0.008, P=0.006), and positively associated with C-reactive protein level ( ß=0.095, 95% CI: 0.054-0.137, P<0.001) and leptin receptor level ( ß=0.090, 95% CI: 0.063-0.117, P<0.001). No association was found between adulthood BMI and resistin levels or between adulthood BMI and insulin-like growth factor-binding protein-3 levels. BMI in early adulthood was found to be negatively associated with only insulin-like growth factor-binding protein-3 levels ( ß=-0.039, 95% CI: -0.068--0.010, P=0.009). Further analysis of adulthood weight gain after the age of 20 revealed that average annual weight gain in adulthood was negatively associated with adiponectin levels and positively associated with 4 other biomarkers. Furthermore, compared with those of women whose weight remained stable, the adiponectin level of women whose weight gain in adulthood exceeded 5.00 kg was much lower ( ß=-0.185, 95% CI: -0.320--0.049, P=0.008), while their insulin-like growth factor-binding protein-3 ( ß=0.389, 95% CI: 0.183-0.594, P<0.001) and leptin receptor ( ß=0.245, 95% CI: 0.048-0.442, P=0.015) levels were higher. Conclusion: Weight gain in adulthood is strongly associated with the changes in obesity-related breast cancer risk biomarkers. Women should maintain a stable weight throughout adulthood and it is preferred that their weight gain should not exceed 5.00 kg.

Causal relationships between breast cancer risk factors based on mammographic features.

BACKGROUND: Mammogram risk scores based on texture and density defined by different brightness thresholds are associated with breast cancer risk differently and could reveal distinct information about breast cancer risk. We aimed to investigate causal relationships between these intercorrelated mammogram risk scores to determine their relevance to breast cancer aetiology. METHODS: We used digitised mammograms for 371 monozygotic twin pairs, aged 40-70 years without a prior diagnosis of breast cancer at the time of mammography, from the Australian Mammographic Density Twins and Sisters Study. We generated normalised, age-adjusted, and standardised risk scores based on textures using the Cirrus algorithm and on three spatially independent dense areas defined by increasing brightness threshold: light areas, bright areas, and brightest areas. Causal inference was made using the Inference about Causation from Examination of FAmilial CONfounding (ICE FALCON) method. RESULTS: The mammogram risk scores were correlated within twin pairs and with each other (r = 0.22-0.81; all P < 0.005). We estimated that 28-92% of the associations between the risk scores could be attributed to causal relationships between the scores, with the rest attributed to familial confounders shared by the scores. There was consistent evidence for positive causal effects: of Cirrus, light areas, and bright areas on the brightest areas (accounting for 34%, 55%, and 85% of the associations, respectively); and of light areas and bright areas on Cirrus (accounting for 37% and 28%, respectively). CONCLUSIONS: In a mammogram, the lighter (less dense) areas have a causal effect on the brightest (highly dense) areas, including through a causal pathway via textural features. These causal relationships help us gain insight into the relative aetiological importance of different mammographic features in breast cancer. For example our findings are consistent with the brightest areas being more aetiologically important than lighter areas for screen-detected breast cancer; conversely, light areas being more aetiologically important for interval breast cancer. Additionally, specific textural features capture aetiologically independent breast cancer risk information from dense areas. These findings highlight the utility of ICE FALCON and family data in decomposing the associations between intercorrelated disease biomarkers into distinct biological pathways.

The role of three-dimensional in vitro models in modelling the inflammatory microenvironment associated with obesity in breast cancer.

Obesity is an established risk factor for breast cancer in postmenopausal women. However, the underlying biological mechanisms of how obesity contributes to breast cancer remains unclear. The inflammatory adipose microenvironment is central to breast cancer progression and has been shown to favour breast cancer cell growth and to reduce efficacy of anti-cancer treatments. Thus, it is imperative to further our understanding of the inflammatory microenvironment seen in breast cancer patients with obesity. Three-dimensional (3D) in vitro models offer a key tool in increasing our understanding of such complex interactions within the adipose microenvironment. This review discusses some of the approaches utilised to recapitulate the breast tumour microenvironment, including various co-culture and 3D in vitro models. We consider how these model systems contribute to the understanding of breast cancer research, with particular focus on the inflammatory tumour microenvironment. This review aims to provide insight and prospective future directions on the utility of such model systems for breast cancer research.