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Background Studies in women of European descent showed an inverse association of dietary vitamin A (retinol and carotenoids) intake with breast cancer risks, mainly in premenopausal women. Objectives We examined whether higher compared with lower levels of dietary vitamin A are associated with reduced breast cancer risks among Black women by estrogen receptor (ER) and menopausal statuses. Methods In this pooled analysis, data were from 3564 breast cancer cases and 11,843 controls (mean ages = 56.4 and 56.3 years, respectively) in the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium. Dietary intake was assessed by FFQs. Multivariable logistic regressions were performed to estimate ORs and 95% CIs for study-specific quintiles of total vitamin A equivalents and individual carotenoids, and a pooled OR was estimated by a random-effect model. Results We observed an inverse association of total vitamin A equivalents with ER-positive breast cancer (quintiles 5 compared with 1: pooled OR: 0.82; 95% CI: 0.67-1.00; P-trend = 0.045). The association was seen among premenopausal women (pooled OR: 0.60; 95% CI: 0.43-0.83; P-trend = 0.004), but not among postmenopausal women (pooled OR: 0.99; 95% CI: 0.77-1.28; P-trend = 0.78). Additionally, there were inverse associations of dietary β-carotene (quintiles 5 compared with 1: pooled OR: 0.70; 95% CI: 0.51-0.95; P-trend = 0.08) and lutein (pooled OR: 0.63; 95% CI: 0.45-0.87; P-trend = 0.020) with ER-positive breast cancer among premenopausal women. There was no evidence for an association of total vitamin A equivalents or individual carotenoids with ER-negative breast cancer, regardless of menopausal status. Conclusions Our findings on dietary vitamin A and breast cancer risks in Black women are consistent with observations in women of European descent and advance the literature showing an inverse association for ER-positive disease.

Background:Evidence suggests etiologic heterogeneity among breast cancer subtypes. Previous studies with six-marker IHC classification of intrinsic subtypes included small numbers of black women.Methods:Using centralized laboratory results for estrogen receptor (ER), progesterone receptor, HER2, proliferation marker, Ki-67, EGFR, and cytokeratin (CK)5/6, we estimated case-only and case–control ORs for established breast cancer risk factors among cases (n = 2,354) and controls (n = 2,932) in the African American Breast Cancer Epidemiology and Risk (AMBER) consortium. ORs were estimated by ER status and intrinsic subtype using adjusted logistic regression.Results:Case-only analyses by ER status showed etiologic heterogeneity by age at menarche, parity (vs. nulliparity), and age at first birth. In case–control analyses for intrinsic subtype, increased body mass index and waist-to-hip ratio (WHR) were associated with increased risk of luminal A subtype, whereas older age at menarche and parity, regardless of breastfeeding, were associated with reduced risk. For basal-like cancers, parity without breastfeeding and increasing WHR were associated with increased risk, whereas breastfeeding and age ≥25 years at first birth were associated with reduced risk among parous women. Basal-like and ER−/HER2+ subtypes had earlier age-at-incidence distribution relative to luminal subtypes.Conclusions:Breast cancer subtypes showed distinct etiologic profiles in the AMBER consortium, a study of more than 5,000 black women with centrally assessed tumor biospecimens.Impact:Among black women, high WHR and parity without breastfeeding are emerging as important intervention points to reduce the incidence of basal-like breast cancer.

Background Compared to U.S. white women, African American women are more likely to die from ductal carcinoma in situ (DCIS). Elucidation of risk factors for DCIS in African American women may provide opportunities for risk reduction. Methods We used data from three epidemiologic studies in the African American Breast Cancer Epidemiology and Risk Consortium to study risk factors for estrogen receptor (ER) positive DCIS (488 cases; 13,830 controls). Results were compared to associations observed for ER+ invasive breast cancer (n = 2,099). Results First degree family history of breast cancer was associated with increased risk of ER+ DCIS [odds ratio (OR): 1.69, 95% confidence interval (CI): 1.31, 2.17]. Oral contraceptive use within the past 10 years (vs. never) was also associated with increased risk (OR: 1.43, 95%CI: 1.03, 1.97), as was late age at first birth (≥25 years vs., Highlights • Few studies of risk factors for ductal carcinoma in situ (DCIS) have evaluated associations for African American women. • We analyzed data from the African American African American Breast Cancer Epidemiology and Risk (AMBER) Consortium. • Family history of breast cancer, reproductive factors, and anthropometric factors were associated with risk of ER+ DCIS. • In general, risk factor associations for ER+ DCIS were similar to those for ER+ invasive breast cancer. • Our findings support a common etiology and pathogenesis between ER+ DICS and ER+ invasive cancer in African American women.

Obesity is a potential risk for several cancers, including postmenopausal, hormone dependent breast cancers. In this review, we summarize recent studies on the impact of obesity on postmenopausal women’s health and discuss several mechanisms that were proposed to increase the risk of breast carcinogenesis.

Simple Summary Breast cancer is the most common cancer among women. It is estimated that 2.3 million new cases of BC are diagnosed globally each year. Based on mRNA gene expression levels, BC can be divided into molecular subtypes that provide insights into new treatment strategies and patient stratifications that impact the management of BC patients. This review addresses the overview on the BC epidemiology, risk factors, classification with an emphasis on molecular types, prognostic biomarkers, as well as possible treatment modalities. Abstract Breast cancer (BC) is the most frequently diagnosed cancer in women worldwide with more than 2 million new cases in 2020. Its incidence and death rates have increased over the last three decades due to the change in risk factor profiles, better cancer registration, and cancer detection. The number of risk factors of BC is significant and includes both the modifiable factors and non-modifiable factors. Currently, about 80% of patients with BC are individuals aged >50. Survival depends on both stage and molecular subtype. Invasive BCs comprise wide spectrum tumors that show a variation concerning their clinical presentation, behavior, and morphology. Based on mRNA gene expression levels, BC can be divided into molecular subtypes (Luminal A, Luminal B, HER2-enriched, and basal-like). The molecular subtypes provide insights into new treatment strategies and patient stratifications that impact the management of BC patients. The eighth edition of TNM classification outlines a new staging system for BC that, in addition to anatomical features, acknowledges biological factors. Treatment of breast cancer is complex and involves a combination of different modalities including surgery, radiotherapy, chemotherapy, hormonal therapy, or biological therapies delivered in diverse sequences.

Resume Le cancer du sein est dans le monde la localisation la plus frequente chez la femme. Cependant les incidences varient de 27/100000* en Asie Centrale-Est et en Afrique a 85–94/100000* (Australie, Amerique du Nord et Europe de l’Ouest). La France se situe parmi les frequences les plus eleves d’Europe. Pour la plupart des pays, l’incidence augmente depuis plus de 40 ans, mais dans quelques pays (USA, Canada, Australie, France…), elle decroit depuis les annees 2000–2005. Cette baisse pourrait etre due a l’importante reduction des traitements hormonaux de la menopause et pourrait etre transitoire. C’est aussi la premiere cause de mortalite par cancer chez les femmes dans presque tous les pays, sauf dans les plus economiquement developpes ou elle est passee au 2eme rang, voire au 1er, apres les cancers du poumon. La mortalite par cancer du sein decroit depuis, une trentaine d’annees dans les pays les plus industrialises comme en France. Diagnostic precoce et amelioration des traitements se partagent cette reussite. En France, la survie a 5 ans est de l’ordre de 88 % et de 78 % a 10 ans, elle est parmi les taux les plus eleves d’Europe de l’Ouest. L’exces de mortalite du aux cancers du sein est donc faible (

When mammography screening programs are fully implemented, interval cancers comprise a substantial proportion of incident breast cancers. Interval cancers may have been overlooked at the last mammography examination or become apparent because they grew so rapidly that the detectable preclinical phase (sojourn time) was shorter than the screening interval. This overview describes the epidemiology, radiological and biological characteristics and time of diagnosis of interval breast cancers in population of mammography screening. Our team retrospectively collected data of symptomatic patients who presented to the West Hertfordshire Trust Breast Unit during the period from 1st of October 2016 until the 30th of September 2017 and identified any interval cancers (screening imaging 40 months prior). Imaging included two-view digital mammogram as well as ultrasound. The total number of cancers diagnosed during this period was 335 patients of which a total of 49 patients (14.6%) were interval cancers, with an average age of 62.42 years; 48 patients (97.9%) had new cancers while one patient (2.1%) had recurrent disease, and 2 patients (4%) had metastatic disease. Average tumour size was 26.79 mm (range 81 mm); 37 patients (75. 5%) had IDC with or without other pathology while average tumour grade was grade 2. Our review demonstrated that interval cancers are more common with invasive high-grade disease; multicentre further studies including larger numbers will be very informative.

Background: It is necessary to investigate the frequency of BRCA1 and BRCA2 mutations in Hakka populations due to the variations in breast cancer epidemiology and genetics. Methods: 359 breast cancer patients and 66 ovarian cancer patients were included in this retrospective clinical study. Mutations of BRCA1 and BRCA2 were detected in blood samples by semiconductor sequencing. Results: The sensitivity of tumor markers including CEA, CA15-3, CA12-5, and CA199 for screening breast cancer was 16.44, 15.11, 8.44, and 7.56%, the combination of these 4 tumor markers reached the highest sensitivity index (31.11%). For ovarian cancer, the tumor markers were CA12-5 (54.05%), HE-4 (54.05%), CA72-4 (51.35%), and CEA (2.70%) in order of decreasing sensitivity. Moreover, the combination of these 4 tumor markers has the best sensitivity (75.68%) for screening ovarian cancer. In breast cancer patients, we found 5 (1.39%) patients with mutations in BRCA1, 13 (3.62%) mutations in BRCA2, and the total carrier rate is 5.01% (18/359). For ovarian cancer patients, the corresponding results were 3 (4.54%) mutations, 2 (3.03%) mutations, and 7.58% (5/66), respectively. The proportion of BRCA mutations was 5.41% (23/425) in breast and ovarian cancer patients of a Hakka population. The pathogenic, likely pathogenic, and benign mutations, and mutations of uncertain significance in this study mainly occurred in exon 14 of the BRCA1 gene, and exon 10 and exon 11 of the BRCA2 gene. Conclusions: Understanding the spectrum and frequency of BRCA1 and BRCA2 mutations in a Hakka population will assist in the prevention and control of hereditary breast and ovarian cancers in this population.

The totality of experimental and epidemiological evidence that ovarian hormones cause breast cancer is sufficiently compelling that epidemiologists are increasingly focused on using the data to develop prevention strategies. Cell division is necessary for the series of genetic changes required for a cell to undergo transformation from normal to a fully malignant phenotype. Breast cancer is characterized by a series of risk factors that emphasize the importance of ovarian steroid hormones in breast cancer etiology. Based on the established effects of oophorectomy in reducing breast cancer risk, Pike, colleagues proposed that the induction of a medical menopause in premenopausal women would result in a substantial reduction in breast cancer incidence. Although hormonal chemoprevention of breast cancer is increasingly promising, there is clearly a need for prevention strategies for breast cancer via life-style change. Although precise age at natural menopause is often difficult to recall in epidemiological studies, ages at natural versus surgical menopause have roughly effects on breast cancer risk.

Background. Data regarding breast cancer epidemiology, treatment and survival in Africa are scarce. We aimed to assess the distribution of breast cancer subtypes in Mozambique and its impact on patients’ treatment and survival. The concordance of biomarker assessment between cytological and histological samples was also evaluated. Methods. Prospective cohort study including 210 patients diagnosed between January 2015 and August 2017, followed to November 2019. Clinicopathological characteristics, treatment, 3-year overall survival (OS) and disease-free survival (DFS) were compared across classic tumour subtypes (oestrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative, HER2-positive and triple-negative breast cancer (TNBC)) and surrogate intrinsic subtypes (St. Gallen classification). Concordance was measured using Cohen’s κ statistics. Results. A total of 51% of patients had ER-positive/HER2-negative tumours, 24% HER2-positive and 25% TNBC. Concordance between cytological and histological samples regarding ER and HER2 status was substantial (κ=0.762 and κ=0.603, respectively). There were no significant differences across subtypes regarding clinical characteristics and treatment, except for HIV positivity and high histological grade (more prevalent among TNBC) or endocrine therapy (higher use among ER-positive/HER2-negative and HER2-positive patients). Three-year OS was 52.5% (95% CI, 44.3% to 60.0%), being higher in ER-positive/HER2-negative (61.1%) compared with HER2-positive (53.2%) and TNBC (31.9%) patients. Adjusted HRs were 1.96 (95% CI, 1.13 to 3.39) among HER2-positive and 3.10 (95% CI, 1.81 to 5.31) among TNBC versus ER-positive/HER2-negative patients. Three-year DFS was 46.6% (95% CI, 38.0% to 54.8%), being lower among TNBC versus ER-positive/HER2-negative patients (HR 2.91; 95% CI, 1.64 to 5.16). Results were similar between surrogate intrinsic subtypes. Conclusion. There was a high proportion of HER2-positive and TNBC among Mozambican patients and their survival was poor compared with ER-positive/HER2-negative patients, partly due to the limited treatment options. A systematic assessment of ER, PR and HER2 status is feasible and may help tailoring and optimise the treatment of patients with breast cancer in low-resource settings, potentially leading to survival gains in this underserved population. We acknowledge the funding support given to the Moza-BC cohort study by the Beginning Investigator Grant for Catalytic Research (BIG Cat) programme, an African Organisation for Research and Training in Cancer (AORTIC) programme with support from the US National Cancer Institute (grant no 59-210-6-004). The funding source had no involvement in the analysis, interpretation of data, writing of the report or decision to submit the manuscript for publication.

Adult-attained height is a marker for underlying mechanisms, such as cell growth, that may also influence postmenopausal breast cancer (BC) risk, perhaps specifically hormone-sensitive BC subtypes. Early life energy restriction may inhibit these mechanisms, resulting in shorter height and a reduced postmenopausal BC risk. Women (62,573) from the Netherlands Cohort Study completed a self-administered questionnaire in 1986 when 55-69 years old, and were followed-up for 20.3 years (case-cohort: N-subcohort = 2,438; N-cases = 3,354). Cox multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated for BC risk overall and by estrogen and progesterone receptor subtypes in relation to height and early life energy restriction during the Hunger Winter, War Years, and Economic Depression. Although energy restriction can only influence longitudinal growth in women exposed before and/or during the growth spurt, it may also influence BC risk when occurring after the growth spurt, possibly through different growth processes. Therefore, Cox analyses were additionally conducted according to timing of energy restriction in relation to the growth spurt. Height was associated with an increased BC risk (HRper 5cm = 1.07, 95%CI:1.01-1.13), particularly hormone receptor-positive BC. Energy restriction before and/or during the growth spurt was associated with a decreased hormone receptor-positive BC risk. Energy restriction during the Hunger Winter increased the estrogen receptor-negative BC risk regardless of the timing of energy restriction. In conclusion, height and energy restriction before and/or during the growth spurt were both associated with hormone receptor-positive BC risk, in the direction as expected, indicating critical exposure windows for hormonal growth-related mechanisms.

The University of Wisconsin Breast Cancer Epidemiology Simulation Model (UWBCS), also referred to as Model W, is a discrete-event microsimulation model that uses a systems engineering approach to replicate breast cancer epidemiology in the US over time. This population-based model simulates the lifetimes of individual women through 4 main model components: breast cancer natural history, detection, treatment, and mortality. A key feature of the UWBCS is that, in addition to specifying a population distribution in tumor growth rates, the model allows for heterogeneity in tumor behavior, with some tumors having limited malignant potential (i.e., would never become fatal in a woman’s lifetime if left untreated) and some tumors being very aggressive based on metastatic spread early in their onset. The model is calibrated to Surveillance, Epidemiology, and End Results (SEER) breast cancer incidence and mortality data from 1975 to 2010, and cross-validated against data from the Wisconsin cancer reporting system. The UWBCS model generates detailed outputs including underlying disease states and observed clinical outcomes by age and calendar year, as well as costs, resource usage, and quality of life associated with screening and treatment. The UWBCS has been recently updated to account for differences in breast cancer detection, treatment, and survival by molecular subtypes (defined by ER/HER2 status), to reflect the recent advances in screening and treatment, and to consider a range of breast cancer risk factors, including breast density, race, body-mass-index, and the use of postmenopausal hormone therapy. Therefore, the model can evaluate novel screening strategies, such as risk-based screening, and can assess breast cancer outcomes by breast cancer molecular subtype. In this article, we describe the most up-to-date version of the UWBCS.

Breast cancer, the leading cause of cancer death for women, can be detected at earlier stages through mammography screening. Therefore, most developed countries implemented population†based mammography screening programs. However, cost of mammography and limited resources in terms of number of trained personnel and diagnostic machines prevent mammography screening to be adopted by many other countries. In fact, even in resource†rich countries, there is a growing concern about cost of mammography screening. In this study, we investigate the optimal allocation of limited mammography resources to screen a population. We propose a constrained partially observable Markov decision process (CPOMDP) model that maximizes total expected quality†adjusted life years of the patients when they are allowed only a limited number of mammography screenings. We use a variable resolution grid†based approximation scheme to convert the CPOMDP model into a mixed†integer linear program and conduct several numerical experiments using breast cancer epidemiology data. We observe that as mammography screening capacity decreases, patients in the 40–49 age group should be given the least priority with respect to screening. We further find that efficient allocation of available resources between patients with different risk levels leads to significant quality†adjusted life year gains, especially for the patients with higher breast cancer risk.

Background The incidence and incidence trends of breast cancer according to molecular subtype are unknown at a population level in France. The registry data enables this study and may give this information, that is crucial to describe and understand breast cancer epidemiology. Methods We estimated the incidence rates of breast cancer for each molecular subtype using data from three cancer registries in France for the period from 2007 to 2012. Molecular subtypes were defined with immunohistochemical data. Poisson models were estimated to modelize the course of breast cancer incidence and to test the trends. Results The study included 12,040 patients diagnosed between 2007 and 2012 in the three administrative areas covered by the registries. There was no significant trends in the proportion of each molecular subtype year by year. The age distribution of incident cases was different depending on the molecular subtypes (p

The Cancer Intervention and Surveillance Modeling Network (CISNET) Breast Cancer Working Group is a consortium of National Cancer Institute–sponsored investigators who use statistical and simulation modeling to evaluate the impact of cancer control interventions on long-term population-level breast cancer outcomes such as incidence and mortality and to determine the impact of different breast cancer control strategies. The CISNET breast cancer models have been continuously funded since 2000. The models have gone through several updates since their inception to reflect advances in the understanding of the molecular basis of breast cancer, changes in the prevalence of common risk factors, and improvements in therapy and early detection technology. This article provides an overview and history of the CISNET breast cancer models, provides an overview of the major changes in the model inputs over time, and presents examples for how CISNET breast cancer models have been used for policy evaluation.

The MISCAN-Fadia microsimulation model uses continuous tumor growth to simulate the natural history of breast cancer and has been used extensively to estimate the impact of screening and adjuvant treatment on breast cancer incidence and mortality trends. The model simulates individual life histories from birth to death, with and without breast cancer, in the presence and in the absence of screening and treatment. Life histories are simulated according to discrete events such as birth, tumor inception, the tumor’s clinical diagnosis diameter in the absence of screening, and death from breast cancer or death from other causes. MISCAN-Fadia consists of 4 main components: demography, natural history of breast cancer, screening, and treatment. Screening impact on the natural history of breast cancer is assessed by simulating continuous tumor growth and the “fatal diameter” concept. This concept implies that tumors diagnosed at a size that is between the screen detection threshold and the fatal diameter are cured, while tumors diagnosed at a diameter larger than the fatal tumor diameter metastasize and lead to breast cancer death. MISCAN-Fadia has been extended by including a different natural history for molecular subtypes based on a tumor’s estrogen receptor (ER) status and human epidermal growth factor receptor 2 (HER2) status. In addition, personalized screening strategies that target women based on their risk such as breast density have been incorporated into the model. This personalized approach to screening will continue to develop in light of potential polygenic risk stratification possibilities and new screening modalities.

Breast cancer epidemiological patterns vary in European countries, which present different incidence rates. Data have suggested that the reduction in breast cancer mortality is not only due to the early detection of the disease, but is, in almost equal part, due to screening and to the advances that have been made in molecular medicine and the development of novel therapies. The aim of the present study is to quantify the actual number of cases of breast cancer present in both of the sexes by calculating the prevalence of silent breast cancer in corpses. To achieve this quantification, bilateral subcutaneous radical mastectomies are performed in corpses of either sex above 40 years of age that lacked any clinical manifestation of the disease, and where the breast cancer or its complications was not the cause of death. Only five publications exist in the international literature based on medico-legal autopsies that were designed to define the ‘natural reservoir’ of the disease. To the best of our knowledge, the present study is the first one to appraise breast tissue via imaging by means of orienting the biopsy incision. In conclusion, to the best of our knowledge, the design of the present study is the first of its type, where image-guided biopsies are used to define the prevalence of silent breast cancer. The study aims to demonstrate that the ‘disease reservoir’ is, in reality, higher than was originally considered to be so. Furthermore, the study aims to contribute towards an improved definition of the disease by determining which tumour profiles potentially do not benefit from aggressive treatments (for example, in case where a high prevalence of low-grade ductal carcinoma in situ is to be detected). According to our pilot study, this analysis represents a feasible protocol.

Although identification of human epidermal growth factor receptor 2 (Her2) positive breast cancer represents one of the greatest advances over the past 3 decades, it has not been studied extensively on a national level.The National Cancer Database is a joint project of the American Cancer Society and the American College of Surgeons and contains data on about 70% of the cancer cases in the United States. Data on Her2 have been collected since 2010 and was used for this study.Of 298,937 cases of invasive breast cancer with known Her2 status diagnosed in 2010 and 2011, 43,485 (14.5%) were Her2 positive. Her2 positivity was greatest in Asian/Pacific Islanders and least in non-Hispanic Whites and was markedly more common in younger women. The incidence of Her2 positive tumors ranged from a low of 13.9% in the Mountain West region to a high of 16.0% in the West South Central region (P.001). Compared with Her2 negative tumors, Her2 positive tumors were larger (2.6 vs 2.2 cm, P.001), more likely to have positive nodes (39% vs 31% P.001), have lymphovascular invasion (30% vs 20%, P.001), and be high grade (56% vs 29%, P.001). There were also differences by histology: invasive ductal 16.4%, invasive lobular 5.5%, tubular 2.3%, inflammatory 36%, and Paget's with invasion 59%. When adjusted for age, race, tumor size, and nodal status Her2 positive tumors were much more likely to receive chemotherapy (odds ratio = 5.5, confidence interval = 5.2 to 6.0) and somewhat less likely to undergo breast preservation (odds ratio = .78, confidence interval = .76 to .80).Her2 positive tumors have distinct epidemiologic, clinical, and treatment characteristics.

Between the years 2010 and 2012, the lifetime probability of developing female breast cancer was 12.3%, or approximately 1 in 8. Worldwide, breast cancer is the most common cancer in women. Survival is increasing. Between 2005 and 2011, the 5-year relative survival was found to be 89%. This is thought to be due to both the increase in utilization of population-wide screening, as well as advances in treatment. Less than 10% of breast cancers can be attributed to an inherited genetic mutation. Breast cancer is more commonly associated with environmental, reproductive, and lifestyle factors, some of which are potentially modifiable.

Background and Objectives: Breast cancer is the most prevalent cancer in women worldwide. Lebanon is a developing country in the Middle East with a prominent breast cancer incidence. The aim of our study was to explore the incidence rates of breast cancer in Lebanon from 2005 to 2015, and compare them to the rates of other countries. Materials and Methods: Breast cancer data for the years 2005&ndash, 2015 was collected from the National Cancer Registry of Lebanon and stratified by gender and age group. Age-specific and age-standardized incidence rates were calculated and analyzed using joinpoint regression. Age-standardized incidence rates in the world population (ASR(w)) were obtained for other countries, from two online databases. Results: Breast cancer was found to be the most prevalent cancer in Lebanon, accounting for 20% of all cancer cases. The average ASR(w) was 96.5 per 100,000. Over the studied period, breast cancer ASR(w) in Lebanon showed a significantly increasing trend with an annual percent change (APC) of +4.6. Moreover, the APC of breast cancer age-specific rates significantly increased for the age groups 45&ndash, 49 (p = 0.013), 50&ndash, 54 (p &lt, 0.001), 55&ndash, 59 (p = 0.001), 60&ndash, 64 (p = 0.002), 65&ndash, 69 (p = 0.003), 70&ndash, 74 (p &lt, 0.001), and 75+ years (p &lt, 0.001). Lebanon had the highest breast cancer ASR(w), when compared to other regional countries, and trailed only behind Denmark, when compared to selected countries from different parts of the world. Conclusions: Breast cancer incidence in Lebanon is among the highest in the world. Future studies should focus on exploring the genetic profile of the Lebanese population in an aim to extrapolate proper prevention guidelines.

In recent years, the application of spatial analysis in the context of epidemiologic surveillance and research has increased exponentially. Today, the use of spatial statistics extend beyond descriptive mapping to analyze and visualize the underlying spatial patterns of human dynamics; offering epidemiologists and public health researchers new and richer ways to visualize illness, and understand of the underlying spatial dynamics of cancer. For cancer prevention and control, such methods facilitate visualization of high risk areas and identification of spatially heterogeneous risk factors, both of which aid in prioritizing regions that would benefit from additional health resources, such as screening programs and treatment services. Although these sophisticated spatial methodologies are widely available, they have been slow to adoption in the field of cancer epidemiology, and conventional “nonspatial” statistical methods are still most commonly used to describe and understand the burden of breast cancer, and the relative contribution of social and geographic disparities. In this chapter, we seek to better understand how geospatial methods are being applied to understand the epidemiology of breast cancer. We conducted a systematic literature review to describe the contexts in which geospatial methods have been employed, including the types of research questions, populations studied, sophistication of the techniques employed, and disciplinary composition of the author groups. We assess the strengths and limitations of these approaches and offer guidance on future directions with spatial breast cancer epidemiology.

Clinical practice guidelines do not sufficiently address the needs of patients with multiple chronic conditions (MCC) as these guidelines focus on single disease management and ignore unique patient-specific conditions. As a result, a non-personalized approach for the management of the patients with MCC leads to adverse events and increases the financial burden on the health care system as over 150 million Americans experience MCC. To this end, we develop a stochastic modeling framework to personalize the management of MCC and provide an exact solution algorithm. We consider the optimal management of preventive care for an index disease (e.g., breast cancer, colorectal cancer, HIV, etc.) while accounting for the existence of a chronic condition (e.g., hypertension, diabetes, Alzheimer's disease, etc.) Our modeling framework is particularly useful for the cases where the chronic condition affects the risk of the index disease. In a case study using real breast cancer epidemiology data, we demonstrate how our modeling framework can be used to personalize breast cancer screening for women with type 2 diabetes. In addition to providing a personalized breast cancer screening schedule for diabetic women, we find some important policy insights that were not previously recognized by the medical community. More specifically, we find that compared to non-diabetic women, diabetic women should be screened less aggressively but screening should end at similar ages. We also find that adherence to the optimal screening policy is more crucial for diabetic women compared to non-diabetic women. Our main insight on screening recommendations also has important resource implications as it leads to fewer screening mammograms. That is, compared to the current national breast cancer screening guidelines, the optimal breast cancer screening policy for diabetic women could save the health care system approximately 2.6 million mammograms annually which translates to $405 million of annual cost savings.

Introduction Previous investigations found elevated mortality after breast cancer in association with biomarkers of persistent organochlorine pesticides in non-occupationally exposed women. We hypothesized that lifetime residential pesticide use, which includes persistent and non-persistent pesticides, would also be associated with increased mortality after breast cancer. Methods A population-based cohort of 1505 women with invasive or in situ breast cancer was interviewed in 1996–1997, shortly after diagnosis, about pre-diagnostic lifetime residential pesticide use. Participants were followed for mortality through 2014 (595 deaths from any cause and 236 from breast cancer, after 17.6 years of follow-up). Pesticides were examined as 15 individual categories; a group of seven used for lawn and garden purposes; a group of eight used for nuisance-pest purposes; and all combined. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and breast cancer-specific mortality. Modification by estrogen receptor (ER) status, body mass index, and long-term residence was examined. Results Ever use (HR = 0.77, 95%CI = 0.63–0.95) and higher lifetime applications (4th quartile: HR = 0.62, 95%CI = 0.47–0.81, ptrend = 0.3) of the lawn and garden group of pesticides were inversely associated with all-cause mortality, compared to never use. The inverse association for lawn and garden pesticide use was limited to ER positive (vs. negative) tumors (pinteraction = 0.05). Nuisance-pest pesticides, and all groups combined, were not associated with all-cause or breast cancer-specific mortality. Conclusions Contrary to our hypothesis, lifetime residential use of lawn and garden pesticides, but not all combined or nuisance-pest pesticides, was inversely associated with all-cause mortality after breast cancer.

In this chapter, several environmental exposures are highlighted that are relevant to breast cancer epidemiology such as natural vegetation/greenness, air pollutants, and outdoor light at night exposures. Each section gives an overview of the rationale and potential mechanisms behind these exposures, followed by a description of the available epidemiologic literature with respect to breast cancer incidence and survival, and then a summary of the challenges and next steps for this area of research. Throughout the chapter, epidemiologic concepts such as exposure measurement, confounding, effect modification and mediation are discussed in context with the environmental exposure. Environmental exposures may play an important role in breast cancer prevention and survival after a diagnosis of breast cancer through a direct influence on biologic pathways and/or via their influence on vital behaviors of energy balance relevant to breast cancer epidemiology (e.g. physical activity and circadian patterns). As one may expect with diseases of long latency such as breast cancer and for studies of environmental exposures, there are challenges to these spatial analyses of breast cancer environmental determinants, particularly with regards to obtaining personal-level measurements of environmental exposures at the appropriate time window within the life course. Understanding the multi-level context of breast cancer incidence and survival after a diagnosis of breast cancer is needed and has potential to explain the geographic variation of breast cancer risk and mortality.

Epidemiology of breast cancer in the Arab region is understudied as compared with Western countries. We aimed to examine breast cancer epidemiology in Arab countries from 1990 to 2016. We analyzed the Global Burden of Disease, 2016 data for breast cancer among women in 22 Arab countries. Epidemiological measures including incidence, mortality, and disability adjusted life years (DALYs) were analyzed for breast cancer in women from 1990 to 2016. We also measured the burden of breast cancer stratified by the sociodemographic index (SDI). Our analysis indicates that the incidence of breast cancer in Arab women has risen over the past 26 years, but is still lower than global averages. In 2016, there were 45,980 new cases (28/100,000) and 20,063 deaths (11/100,000) in the region. The burden of breast cancer as estimated by DALYs was also lower than the global rates and tended to increase with increasing SDI. Although some studies have reported that Arab women present with breast cancer at a younger age, our analysis of age-specific rates, indicates that this is not statistically significant. Our findings indicate that a comprehensive plan to improve public awareness, screening, diagnosis, and treatment is required to reduce the growing burden of breast cancer in the Arab world.

Leveraging population-distinct linkage equilibrium (LD) patterns, trans-ethnic follow-up of variants discovered from genome-wide association studies (GWAS) has proved to be useful in facilitating the identification of bona fide causal variants. We previously developed the preferential LD approach, a novel method that successfully identified causal variants driving the GWAS signals within European-descent populations even when the causal variants were only weakly linked with the GWAS-discovered variants. To evaluate the performance of our approach in a trans-ethnic setting, we applied it to follow up breast cancer GWAS hits identified mostly from populations of European ancestry in African Americans (AA). We evaluated 74 breast cancer GWAS variants in 8,315 AA women from the African American Breast Cancer Epidemiology and Risk (AMBER) consortium. Only 27% of them were associated with breast cancer risk at significance level α=0.05, suggesting race-specificity of the identified breast cancer risk loci. We followed up on those replicated GWAS hits in the AMBER consortium utilizing the preferential LD approach, to search for causal variants or better breast cancer markers from the 1000 Genomes variant catalog. Our approach identified stronger breast cancer markers for 80% of the GWAS hits with at least nominal breast cancer association, and in 81% of these cases, the marker identified was among the top 10 of all 1000 Genomes variants in the corresponding locus. The results support trans-ethnic application of the preferential LD approach in search for candidate causal variants, and may have implications for future genetic research of breast cancer in AA women.

Breast cancer is the most common neoplasm diagnosed amongst women worldwide and is the leading cause of female cancer death. However, breast cancer in China is not comprehensively understood compared with Westernised countries, although the 5-year prevalence statistics indicate that approximately 11 % of worldwide breast cancer occurs in China and that the incidence has increased rapidly in recent decades. This paper reviews the descriptive epidemiology of Chinese breast cancer in terms of incidence, mortality, survival and prevalence, and explores relevant factors such as age of manifestation and geographic locations. The statistics are compared with data from the Westernised world with particular emphasis on the United States and Australia. Potential causal agents responsible for differences in breast cancer epidemiology between Chinese and other populations are also explored. The need to minimise variability and discrepancies in methods of data acquisition, analysis and presentation is highlighted.