Epidemiologic Studies Of Breast Cancer Research Articles

Comparative epidemiological study of breast cancer in humans and canine mammary tumors: insights from Portugal

Dogs spontaneously develop mammary gland tumors (MGT) and exhibit striking similarities in clinical and epidemiological characteristics to human breast cancer (HBC). Descriptive and comparative analysis of HBC and canine MGT with a focus on evaluating similarities and geographical distribution were the aims of this study. HBC cases were obtained from North Regional Oncological Registry (RORENO) (2010–2015) and canine MGT cases from Vet-OncoNet (2019–2022). Analyses were performed based on published and well accepted classification systems (ICD-O-3.2 for humans and Vet-ICD-O-canine-1). Age-standardized incidence risks (ASIR) of Porto district municipalities were calculated using 2021 Portuguese census (INE) and data from the Portuguese animal registration system (SIAC). Among 7,674 HBC cases and 1,140 MGT cases, a similar age and sex distribution pattern was observed. Approximately 69.2% of HBC cases were between 40 and 69 years old, while 66.9% of MGT cases were diagnosed between 7 and 12 years old (mean age of 9.6 years, SD = 2.6). In women, Invasive breast carcinoma (8500/3) was the most common histological type (n = 5,679, 74%) while in dogs it was the Complex Carcinoma (8983.1/3) (n = 205, 39%). Cocker and Yorkshire Terriers exhibited the highest relative risks (3.2 and 1.6, p < 0.05, respectively) when compared to cross breed dogs. The municipalities' ASIR of the two species exhibited a high correlation (R = 0.85, p < 0.01) and the spatial cluster analysis revealed similar geographic hotspots. Also, higher ASIR values both in women and dogs were more frequently found in urbanized areas compared to rural areas. This research sheds light on the shared features and geographical correlation between HBC and canine MGT, highlighting the potential of cross-species environmental oncology studies.

Application of Metabolomics to Epidemiologic Studies of Breast Cancer: New Perspectives for Etiology and Prevention.

To provide an overview on how the application of metabolomics (high-throughput characterization of metabolites from cells, organs, tissues, or biofluids) to population-based studies may inform our understanding of breast cancer etiology. We evaluated studies that applied metabolomic analyses to prediagnostic blood samples from prospective epidemiologic studies to identify circulating metabolites associated with breast cancer risk, overall and by breast cancer subtype and menopausal status. We provide some important considerations for the application and interpretation of metabolomics approaches in this context. Overall, specific lipids and amino acids were indicated as the most common metabolite classes associated with breast cancer development. However, comparison of results across studies is challenging because of heterogeneity in laboratory techniques, analytical methods, sample size, and applied statistical methods. Metabolomics is being increasingly applied to population-based studies for the identification of new etiologic hypotheses and/or mechanisms related to breast cancer development. Despite its success in applications to epidemiology, studies of larger sample size with detailed information on menopausal status, breast cancer subtypes, and repeated biologic samples collected over time are needed to improve comparison of results between studies and enhance validation of results, allowing potential clinical translation of findings.

ЭПИДЕМИОЛОГИЧЕСКИЙ АНАЛИЗ РАКА МОЛОЧНОЙ ЖЕЛЕЗЫ И ОСОБЕННОСТИ ОКАЗАНИЯ МЕДИЦИНСКОЙ ПОМОЩИ ЖЕНЩИНАМ В ПРИАРКТИЧЕСКОМ РЕГИОНЕ СЕВЕРО-ЗАПАДА РОССИИ (АРХАНГЕЛЬСКАЯ ОБЛАСТЬ)

Relevance: epidemiological studies of breast cancer are due to the fact that this nosological form is one of the leading among all other malignant neoplasms detected in the female population not only of the Arkhangelsk region, but also of the Russian Federation. Over the past decade, there has been an increase in the incidence of this pathology. The article analyzes the statistical indicators of morbidity and mortality from breast cancer from 2010 to 2020; the results obtained in the Arkhangelsk region are compared with those in the Russian Federation as a whole. The aim of the study is to identify the features of the prevalence of breast cancer and its consequences among the female population living in the Arkhangelsk region, as well as problems in the system of prevention, early diagnosis, medical care and rehabilitation of patients. Materials and methods: statistical data on the situation associated with cancer incidence in one of the largest and most densely populated Arctic territories (Arkhangelsk region) were used. Research results: over the past decade, from 2010 to 2019, the incidence of breast cancer in women living in the Arkhangelsk region has steadily increased; only in 2020 there was a significant decrease in this indicator. At the same time, breast cancer mortality was gradually decreasing. Over the past 5 years, there has been a clear trend of success in early diagnosis of breast cancer, which significantly increases the chances of survival in the fight against this disease, improves the quality of life of patients. Such positive results are largely due to the implementation of the federal program "Fight against oncological diseases" in each region.

Breast Cancer Risk, Screening, and Prevalence Among Sexual Minority Women: An Analysis of the National Health Interview Survey.

Purpose: Sexual minority women (SMW) may have a different distribution of breast cancer risk factors than their heterosexual peers. Epidemiologic studies of breast cancer in SMW have been limited, and many use only proxy variables to identify SMW in data sets, introducing selection bias. We utilized National Health Interview Survey (NHIS) data to compare breast cancer risk factors, screening, and prevalence between SMW and non-SMW. Methods: We identified female respondents to the NHIS from 2013 to 2017, selected women ≥40 years old and stratified by sexual orientation. We compared demographics and health maintenance variables and prevalence of breast cancer diagnosis between groups and performed a multivariable analysis of breast cancer risk. Results: Of 58,378 women ≥40 years old, 1162 (2.0%) were identified as SMW. SMW were younger and more likely to use tobacco and alcohol, be younger at menarche, and be nulliparous. SMW also reported less preventive care, and despite reporting equivalent rates of mammography, were more likely to obtain mammograms due to an identifiable problem and not simply for screening purposes. Prevalence of breast cancer was similar between SMW and non-SMW (4.7% vs. 5.0%, p = 0.67), and SMW status was not associated with breast cancer diagnosis on univariate and multivariable logistic regression (p = 0.14 and p = 0.07, respectively). Conclusion: Despite finding no difference in breast cancer prevalence between SMW and non-SMW, there was evidence for differences in the utilization of breast care. Further studies of breast cancer incidence, characteristics (including subtype and stage), treatment, and survival for SMW are needed.

Clinical and pathological characteristics of patients with overexpressed her 2 breast cancer in the national cohort study – Amazona III

Introduction: HER2 overexpressed breast cancer (+) is observed at around 15-20%. The introduction of target therapies in this subtype changed the prognosis of these patients, improving mortality and reducing surgical morbidity when neoadjuvant therapy allows downstaging of breast and axillary surgery. A recent publication with 1,310 samples from Brazilian patients described 20% of HER-2 + tumors. There are few epidemiological studies evaluating patients in our population. The Amazona III study evaluated the epidemiology of breast cancer in a sample of the Brazilian population including 2,950 patients from 23 Brazilian hospitals, completed in 2018. Objective: To characterize the frequency of positive HER-2 breast cancer in patients in the Amazona III study and its clinical characteristics. Method: Prospective, multicenter cohort study. All female patients with invasive breast cancer over 18 years of age included in the Amazona III Project were considered eligible. Immunohistochemical determination was made according to the pathology laboratory of each center. Results: Of the 2,950 study participants, 643 (21%) were HER2 +, 71% from the Unified Health System (SUS) and 28.9% from the complementary system. Most had grade 2 (52.6%) or 3 (36.4%), were post-menopausal (53%), positive estrogen receptor (71.9%), and did not undergo neoadjuvant therapy (52%). As for the number of lymph nodes, 45% were positive lymph nodes, with cN1 (27%), cN2 (12%), and cN3 (5%). 49% had positive lymph nodes in SUS and 37% in the private system. The rate of conservative breast surgery was similar in both groups, being around 46%. Conclusion: The prevalence of HER-2 + in patients included in the Amazona Study III (current epidemiological study of breast cancer in Brazil) is compatible with data from the literature. The prevalence of positive lymph node at diagnosis is high, especially in SUS (49%), therefore the impact of access to therapies that increase the chance of increasing overall survival, decreasing invasive recurrence, and decreasing surgical morbidity must be evaluated.

A nomogram for predicting the HER2 status in female patients with breast cancer in China: a nationwide, multicenter, 10-year epidemiological study

BackgroundThe concordance rate of human epidermal growth factor receptor 2 (HER2) status between core needle biopsy (CNB) and subsequent excisional biopsies of the same tumor varies from 81 to 96%, which may cause inappropriate neoadjuvant therapy that impair the potential benefit from HER2 targeted therapy for patients. This study aimed to establish a nomogram to predict the HER2 status pre-operatively as an auxiliary diagnosis to CNB assessment.MethodsAmong 4211 breast cancer patients cataloged in the Nation-wide Multicenter 10-year Retrospective Clinical Epidemiological Study of Breast Cancer in China, 2291 patients with complete relevant information were included in this study, which were further randomized 3:1 and divided into a training set and a validation set. The nomogram was established based on independent predictors of HER2 positivity recognized by logistic regression analysis and further validated internally and externally.ResultsThe multivariate logistic regression analysis showed that T-stage, N-stage, estrogen receptor (ER) status, progesterone receptor (PR) status were independent predictors for HER2 status. The nomogram was thereby constructed by those independent predictors as well as histology type. The areas under the receiver operating characteristic curve (AUC) of the training set and the validation set were 0.636 and 0.681, respectively. The calibration plots demonstrated good fitness of the nomogram for HER2 status prediction. With the optimal cutoff value, the nomogram yielded 80.0% sensitivity, 43.1% specificity in the training set and 81.1% sensitivity, 49.8% specificity in the validation set.ConclusionsThe present nomogram can provide valuable information on HER2 status and combined with standard CNB assessment, clinicians could make more appropriate decision on neoadjuvant therapy of breast cancer.

Development of a FFQ for breast cancer survivors in Korea.

Diet may play an important role in breast cancer recurrence or survival, and therefore assessment of long-term diet among breast cancer survivors is important in breast cancer survivorship research. Given that the diet of breast cancer survivors may differ from that of the general population, the use of a FFQ specific to this group may be needed. The objective of this study was to develop a FFQ for breast cancer survivors, the most commonly used tool to measure long-term dietary patterns in nutritional epidemiological studies. We collected information on the foods and amounts of foods consumed using 3-d dietary records from a total of 192 women who had been diagnosed with stage I-III breast cancers and had undergone breast cancer surgery at least 6 months before the baseline study. A total of 1254 foods and dishes consumed were re-grouped by the similarity of the main ingredients and/or serving units, and several dishes commonly consumed among the Korean population were added. After we performed contribution analyses and variability analyses to detect between-person variation for selected nutrients, we listed a total of 123 foods and dishes for the FFQ specific to breast cancer survivors. Our breast cancer survivor-specific FFQ can be used to estimate long-term dietary intake and to examine its association with breast cancer prognosis in epidemiological studies of breast cancer in Korea.

Admixture Mapping of African-American Women in the AMBER Consortium Identifies New Loci for Breast Cancer and Estrogen-Receptor Subtypes.

Recent genetic admixture coupled with striking differences in incidence of estrogen receptor (ER) breast cancer subtypes, as well as severity, between women of African and European ancestry, provides an excellent rationale for performing admixture mapping in African American women with breast cancer risk. We performed the largest breast cancer admixture mapping study with in African American women to identify novel genomic regions associated with the disease. We conducted a genome-wide admixture scan using 2,624 autosomal ancestry informative markers (AIMs) in 3,629 breast cancer cases (including 1,968 ER-positive, 1093 ER-negative, and 601 triple-negative) and 4,658 controls from the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium, a collaborative study of four large geographically different epidemiological studies of breast cancer in African American women. We used an independent case-control study to test for SNP association in regions with genome-wide significant admixture signals. We found two novel genome-wide significant regions of excess African ancestry, 4p16.1 and 17q25.1, associated with ER-positive breast cancer. Two regions known to harbor breast cancer variants, 10q26 and 11q13, were also identified with excess of African ancestry. Fine-mapping of the identified genome-wide significant regions suggests the presence of significant genetic associations with ER-positive breast cancer in 4p16.1 and 11q13. In summary, we identified three novel genomic regions associated with breast cancer risk by ER status, suggesting that additional previously unidentified variants may contribute to the racial differences in breast cancer risk in the African American population.

A Note on the Mantel-Haenszel Estimators When the Common Effect Assumptions Are Violated

Abstract The Mantel-Haenszel estimators for the common effect parameters of stratified 2×2 tables have been widely adopted in epidemiological and clinical studies for controlling the effects of confounding factors. Although the Mantel-Haenszel estimators are simple and effective estimating methods, the correctness of the common effect assumptions cannot be justified in general practices. Also then, the targeted “common effect parameters” do not exist. Under these settings, even if the Mantel-Haenszel estimators have desirable properties, it is quite uncertain what they estimate and how the estimates are interpreted. In this article, we conducted theoretical evaluations for their asymptotic behaviors when the common effect assumptions are violated. We explicitly showed that the Mantel-Haenszel estimators converge to weighted averages of stratum-specific effect parameters and they can be interpreted as intuitive summaries of the stratum-specific effect measures. Also, the Mantel-Haenszel estimators correspond to the standardized effect measures on standard distributions of stratification variables to be the total cohort, approximately. In addition, the ordinary sandwich-type variance estimators are still valid for quantifying variabilities of the Mantel-Haenszel estimators. We implemented numerical studies based on two epidemiologic studies of breast cancer and schizophrenia for evaluating empirical properties of these estimators, and confirmed general validities of these theoretical results.

Abstract B21: Molecular epidemiological studies of breast cancer in Puerto Rican women and association with cancer health disparities

Abstract Background: Breast cancer (BC) represents approximately 32% of the cancer cases diagnosed in Puerto Rican women and the principal cancer related death in women this population. BC is a complex disease whose risk is influenced by genetic, environmental and epigenetic factors. Although BC incidence among island Puerto Ricans is lower than in the USA, the rate incidence has been increasing 1.3% each year since 1987. Objective: Our aim is to present key findings of a large population study on the molecular epidemiology of BC in Puerto Rican women. We recently completed the recruitment of nearly 1,200 women in a seven-year molecular epidemiology study focused on the role of DNA repair capacity (DRC) as a risk factor for BC. As part of that study, we gathered extensive epidemiological data on risk factors for BC in Puerto Rican women. Methods: A 7-page epidemiological questionnaire was utilized for soliciting information on BC risk factors in relation to familial, occupational, and other variables. A total of 502 women with BC and 685 controls were studied. Crude and multiple logistic regression-derived adjusted odds ratios were used as indicators of the associations between BC and the variables under study. DRC was measured in lymphocytes using a host cell reactivation assay with a luciferase reporter gene. Results: Age is an important risk factor for BC. Women of the 41-60 years of age group had the highest BC risk followed by women with 61 years or more (OR: 2.1, 95%CI 1.3-3.3, OR 1.6, 95%CI 1.2-2.2). Marital status also plays a role on BC risk with single women and widows being the higher risk groups (OR: 2.3 95% CI 1.3-4.0, and OR: 1.8 95%CI 0.9-3.5, respectively). Education was also an important risk factor; women with lower levels of education had a higher BC risk (OR: 3.5 95%CI 1.5- 7.8). Family history of cancer (non BC) and history of BC were both associated with an increase in BC risk (OR 1.8, 95% CI 1.3-2.5). Parity status was associated with a decreased BC risk in women who had at least three full term pregnancies. A higher protection was found in women who had given birth in the 20-29 years of age group (OR 0.6, 95% CI 0.4-0.9). This protection decreased as childbirth age increased. A low DRC was found to be a strong risk factor for BC. DRC was found to have a dose response relationship with women with the lowest levels being the ones with the higher risk (low DRC OR: 14.6 95% CI 9.7-21.9). Women with BC had a 30% reduced odds of multivitamin intake and 40% reduced odds of calcium intake as compared to controls (OR = 0.7; 95% CI: 0.5, 0.9 for multivitamins and OR = 0.6; 95% CI: 0.4, 0.9 for calcium). Women with low DRC had 50% lower odds of taking calcium and 30% lower odds of currently taking vitamins OR = 0.5 (95% CI, 0.4-0.7; P = .001) for calcium and (2) OR = 0.7 (95% CI, 0.5-0.9.1; P = .047) for vitamins. Women with low DRC had 50% lower odds of taking calcium and 30% lower odds of currently taking vitamins OR = 0.5 (95% CI, 0.4-0.7; P = .001) for calcium and (2) OR = 0.7 (95% CI, 0.5-0.9.1; P = .047) for vitamins. Conclusions: Our study clearly shows the critical importance that DRC exerts as a risk factor for BC. Furthermore, the study provides a more comprehensive understanding of risk factors associated with BC in Puerto Rican women. The identification of higher risk individuals among our particular population can help target the population needing the most effective preventive measures. Supported by grants from the NCI Center to Reduce Health Disparities through the NIH-MBRS Program grants S06 GM008239-20, 1SCA157250 and 9SC1CA182846-04. Citation Format: Jaime Matta, Carmen Ortiz, Manuel Bayona, Carolina Alvarez-Garriga, Luisa Morales. Molecular epidemiological studies of breast cancer in Puerto Rican women and association with cancer health disparities. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr B21. doi:10.1158/1538-7755.DISP13-B21

Voluntary participation and comprehension of informed consent in a genetic epidemiological study of breast cancer in Nigeria.

BackgroundStudies on informed consent to medical research conducted in low or middle-income settings have increased, including empirical investigations of consent to genetic research. We investigated voluntary participation and comprehension of informed consent among women involved in a genetic epidemiological study on breast cancer in an urban setting of Nigeria comparing women in the case and control groups.MethodsSurveys were administered in face-to-face interviews with 215 participants following their enrollment in the genetic study (106 patients, 109 controls). Audio-taped in-depth interviews were conducted with a sub-sample of 17 (8%) women who completed the survey.ResultsThe majority of all participants reported being told that participation in the genetic study was voluntary (97%), that they did not feel pressured to participate in the study (99%), and that they could withdraw from the study (81%). The majority of the breast cancer patients (83%) compared to 58% of women in the control group reported that the study purpose was to learn about the genetic inheritance of breast cancer (OR 3.44; 95% CI =1.66, 7.14, p value = 0.001). Most participants reported being told about study procedures (95%) and study benefits (98%). Sixty-eight percent of the patients, compared to 47% of the control group reported being told about study risks (p-value <0.001). Of the 165 married women, 19% reported asking permission from their husbands to enroll in the breast cancer study; no one sought permission from local elders. In-depth interviews highlight the use of persuasion and negotiation between a wife and her husband regarding study participation.ConclusionsThe global expansion of genetic and genomic research highlights our need to understand informed consent practices for studies in ethnically diverse cultural environments such as Africa. Quantitative and qualitative empirical investigations of the informed consent process for genetic and genomic research will further our knowledge of complex issues associated with communication of information, comprehension, decisional authority and voluntary participation. In the future, the development and testing of innovative strategies to promote voluntary participation and comprehension of the goals of genomic research will contribute to our understanding of strategies that enhance the consent process.

A collaborative study of the etiology of breast cancer subtypes in African American women: the AMBER consortium

Breast cancer is a heterogeneous disease, with at least five intrinsic subtypes defined by molecular characteristics. Tumors that express the estrogen receptor (ER+) have better outcomes than ER- tumors, due in part to the success of hormonal therapies that target ER+ tumors. The incidence of ER- breast cancer, and the subset of ER- cancers that are basal-like, is about twice as high among African American (AA) women as among US women of European descent (EA). This disparity appears to explain, in part, the disproportionately high mortality from breast cancer that occurs in AA women. Epidemiologic research on breast cancer in AA women lags behind research in EA women. Here, we review differences in the etiology of breast cancer subtypes among AA women and describe a new consortium of ongoing studies of breast cancer in AA women. We combined samples and data from four large epidemiologic studies of breast cancer in AA women, two cohort and two case-control, creating the African American Breast Cancer Epidemiology and Risk consortium. Tumor tissue is obtained and stored in tissue microarrays, with assays of molecular markers carried out at a pathology core. Genotyping, carried out centrally, includes a whole exome SNP array and over 180,000 custom SNPs for fine-mapping of genome-wide association studies loci and candidate pathways. To date, questionnaire data from 5,739 breast cancer cases and 14,273 controls have been harmonized. Genotyping of the first 3,200 cases and 3,700 controls is underway, with a total of 6,000 each expected by the end of the study period. The new consortium will likely have sufficient statistical power to assess potential risk factors, both genetic and non-genetic, in relation to specific subtypes of breast cancer in AA women.

Serum Factors and Clinical Characteristics Associated with Serum E-Screen Activity

The E-Screen bioassay can measure the mitogenicity of human serum and thus may be useful as a biomarker in epidemiologic studies of breast cancer. While the assay's MCF-7 cells are known to proliferate in response to estrogen, the specific determinants of variation in E-Screen activity in human serum samples are poorly understood. We sought to identify serum molecules and patient characteristics associated with serum E-Screen activity among postmenopausal women. Postmenopausal women (N = 219) aged 55 to 70 years with no history of postmenopausal hormone use or breast cancer completed a questionnaire and provided a blood sample. Serum was analyzed for E-Screen activity and a variety of molecules including sex hormones, growth factors, and environmental chemicals. Stepwise selection procedures were used to identify correlates of E-Screen activity. Serum samples from all women had detectable E-Screen activity, with a median estradiol equivalents value of 0.027 ng/mL and interquartile range of 0.018-0.036 ng/mL. In the final multivariable-adjusted model, serum E-Screen activity was positively associated with serum estradiol, estrone, insulin-like growth factor-binding protein (IGFBP)-3, and testosterone levels (all P < 0.05), as well as body mass index (P = 0.03). Serum E-Screen activity was lower among women with higher SHBG (P < 0.0001) and progesterone levels (P = 0.03). Serum E-Screen activity varies according to levels of endogenous estrogens and other serum molecules. Obesity appears to confer additional serum mitogenicity beyond its impact on the measured hormones and growth factors. By capturing mitogenicity due to a variety of patient and serum factors, the E-Screen may provide advantages for use as a biomarker in breast cancer studies.

Reconstruction of absorbed doses to fibroglandular tissue of the breast of women undergoing mammography (1960 to the present).

The assessment of potential benefits versus harms from mammographic examinations as described in the controversial breast cancer screening recommendations of the U.S. Preventive Task Force included limited consideration of absorbed dose to the fibroglandular tissue of the breast (glandular tissue dose), the tissue at risk for breast cancer. Epidemiological studies on cancer risks associated with diagnostic radiological examinations often lack accurate information on glandular tissue dose, and there is a clear need for better estimates of these doses. Our objective was to develop a quantitative summary of glandular tissue doses from mammography by considering sources of variation over time in key parameters, including imaging protocols, X-ray target materials, voltage, filtration, incident air kerma, compressed breast thickness, and breast composition. We estimated the minimum, maximum and mean values for glandular tissue dose for populations of exposed women within 5-year periods from 1960 to the present, with the minimum to maximum range likely including 90% to 95% of the entirety of the dose range from mammography in North America and Europe. Glandular tissue dose from a single view in mammography is presently about 2 mGy, about one-sixth the dose in the 1960s. The ratio of our estimates of maximum to minimum glandular tissue doses for average-size breasts was about 100 in the 1960s compared to a ratio of about 5 in recent years. Findings from our analysis provide quantitative information on glandular tissue doses from mammographic examinations that can be used in epidemiological studies of breast cancer.

Implications of single nucleotide polymorphisms in CD44 exon 2 for risk of breast cancer

CD44 is a cell-surface glycoprotein involved in many cellular functions including lymphocyte activation, recirculation and homing, hematopoiesis and tumor metastasis, suggesting that CD44 may play an important role in breast cancer development. In this study, we examined whether CD44 exon 2 polymorphisms are associated with increased susceptibility to breast cancer. Direct nucleotide sequencing analysis showed that multiple single nucleotide polymorphisms were present in the CD44 exon 2 coding region in female patients with breast cancer. There was no significant difference in the frequency of any one single nucleotide polymorphism in the CD44 exon 2 coding region between patients with breast cancer and normal donors. However, CD44 polymorphisms in the CD44 exon 2 coding region were identified in approximately 40% of patients with breast cancer, which was significantly higher than in normal donors (odds ratio, 9.34; 95% confidence interval = 2.58-33.82; P < 0.0001). The Wilcoxon-Mann-Whitney test analysis showed that the patients with the CD44 polymorphisms in CD44 exon 2 coding sequence had breast cancer at earlier ages, 49 ± 3 versus 62 ± 2 years (P < 0.0005), and larger tumor burdens (4.9 ± 1.22 vs. 1.6 ± 0.15 mm, P < 0.01) at the time of diagnosis. Interestingly, African-American female patients having the CD44 polymorphisms in CD44 exon 2 coding sequence were diagnosed with breast cancer at very young age (41 ± 2 years). Our results show that CD44 exon 2 polymorphisms are associated with breast cancer development, and such analysis may be effectively used in the evaluation of risk, prediction of cancer, prevention, diagnosis, and epidemiological studies of breast cancer.

Using cancer registry data: agreement in cause-of-death data between the Ontario Cancer Registry and a longitudinal study of breast cancer patients

Data from the Ontario Cancer Registry (OCR) were compared with data from a multi-centred prospective cohort of 1655 node-negative breast cancer patients with intensive clinical follow-up. Agreement in cause of death was evaluated using kappa statistics. The accuracy of OCR classification was evaluated against the Mount Sinai Hospital (MSH) study oncologist's interpretation of intensely followed, cohort-collected data as the reference standard. The two sources showed a high level of agreement (kappa statistic [kappa] = 0.88; 95% confidence interval [CI]: 0.86, 0.90) in vital status and cause of death. Among those cases where both sources reported a death, the OCR had a sensitivity of 95% (95% CI: 90.5, 98.8) and a specificity of 88% (95% CI: 79.6, 92.4). The OCR is a valuable tool for epidemiologic studies of breast cancer to acquire adequate and easily attainable cause-of-death information.

Prevalent cases in observational studies of cancer survival: do they bias hazard ratio estimates?

Observational epidemiological studies often include prevalent cases recruited at various times past diagnosis. This left truncation can be dealt with in non-parametric (Kaplan–Meier) and semi-parametric (Cox) time-to-event analyses, theoretically generating an unbiased hazard ratio (HR) when the proportional hazards (PH) assumption holds. However, concern remains that inclusion of prevalent cases in survival analysis results inevitably in HR bias. We used data on three well-established breast cancer prognosticators – clinical stage, histopathological grade and oestrogen receptor (ER) status – from the SEARCH study, a population-based study including 4470 invasive breast cancer cases (incident and prevalent), to evaluate empirically the effectiveness of allowing for left truncation in limiting HR bias. We found that HRs of prognostic factors changed over time and used extended Cox models incorporating time-dependent covariates. When comparing Cox models restricted to subjects ascertained within six months of diagnosis (incident cases) to models based on the full data set allowing for left truncation, we found no difference in parameter estimates (P=0.90, 0.32 and 0.95, for stage, grade and ER status respectively). Our results show that use of prevalent cases in an observational epidemiological study of breast cancer does not bias the HR in a left truncation Cox survival analysis, provided the PH assumption holds true.

Exposure to Occupational Contaminants and Risk of Male Breast Cancer: A European Case-Control Study

P-171 Abstract: Several environmental exposures have been suspected to play a role in breast cancer etiology, including organochlorine pesticides or other endocrine disrupting chemicals, polycyclic aromatic hydrocarbons (PAHs), and organic solvents, but epidemiological studies of breast cancer have produced inconsistent results. Exposure to these contaminants may also take place in occupational settings. Although male breast cancer is a rare disease, the study of breast cancers in males offers several advantages over a study of breast cancer in females because occupational exposures are usually much higher, and hence more easily assessed in men than in women, and because confounding or effect modification from reproductive risk factors cannot occur. We investigated occupational risk factors for male breast cancer in a European multicenter population-based case-control study that permitted to identify a relatively large numbers of cases. The study included 104 cases of male breast cancer aged 35 to 70 years and 2106 controls in eight European countries. Controls were selected from population registers in all countries, with the exception of Spain and Portugal where colon cancer controls only were available. All study subjects were interviewed across Europe using the same structured questionnaire that included a detailed work history. Occupational exposures to pesticides, PCBs, PAHs, alkylphenols, bisphenol-A, and phthalates were identified through a job-exposure matrix and then individually assessed by an expert using the detailed job description. A job-exposure matrix for petroleum solvents (e.g., benzene, white spirit) is also used. Analyses are carried out to identify the job groups at increased risk for male breast cancer and to examine breast cancer risk according to exposure indicators for specific chemicals. A statistically significant increased risk was observed in printers (OR=2.8 95%CI), painters (OR=2.5 95%CI 1.1–5.7), foundry workers (OR=4.6 95% CI 1.3–17.0), and motor vehicle mechanics (OR=2.0 95% CI 1.1–4.8). Workers in these occupational groups may have been exposed to suspected carcinogens for breast cancer, including organic solvents, gasoline, PAHs and combustion products. Confounding from other risk factors for male breast cancer such as alcohol drinking could not explain these results. The analyses for the specific occupational exposures will permit to further scrutinize these findings. Our results confirm that environmental factors may play a role in breast cancer, and suggest that additional studies on environmental factors in female breast cancer should be conducted.

CYP3A4 Polymorphisms--Potential Risk Factors for Breast and Prostate Cancer: A HuGE Review

The steroid hydroxylase CYP3A4 is the most abundant P-450 enzyme in the human liver, and CYP3A enzymes metabolize more than 50% of prescription drugs. The CYP3A4 gene is expressed in the liver, gut, colon, prostate, and breast. Individual variation in CYP3A4 may play a role in breast and prostate carcinogenesis through modulation of sex hormone metabolite levels. Alternatively, CYP3A4 can metabolically activate exogenous carcinogens. CYP3A4 activity varies widely in humans, and more than 78 DNA sequence polymorphisms are known. These observations prompted the hypothesis that variant CYP3A4 may be involved in breast and prostate cancer. Two epidemiologic studies of breast cancer and five of prostate cancer examined CYP3A4 genotypes. A US study showed that inheritance of CYP3A4*1B correlates with early menarche, a breast cancer risk factor. However, an Australian breast cancer case-control study found no association with CYP3A4*1B. Two Scottish prospective studies showed CYP3A4*1B to be a risk factor for prostate cancer among men with benign prostatic hyperplasia. Three other studies were undertaken in the United States: two were case-only studies and the other was a case-sibling control study. Although results for African Americans were inconsistent, these studies suggested that CYP3A4*1B was associated with markers of advanced disease. These observations support the notion that development of robust, conventional molecular epidemiologic case-control studies to address these questions, including gene-gene and gene-environment interactions, will be timely.

Reproductive and anthropometric factors in relation to the risk of lobular and ductal breast carcinoma among women 65–79 years of age

Use of combined estrogen-progestin hormone replacement therapy appears to be associated with an increased risk of invasive lobular breast carcinomas (ILC) and, to a lesser degree, with risk of invasive ductal carcinoma (IDC). Conceivably, ILCs are more hormonally responsive and so may be more strongly associated than IDCs with reproductive and anthropometric characteristics that can influence hormone levels. However, few epidemiologic studies of breast cancer have evaluated these factors by histologic type. We conducted a population-based case-control study of women aged 65-79 years in western Washington State. Responses from 975 women diagnosed with breast cancer during 1997-1999 were compared to those of 1,007 controls. Associations between various reproductive and anthropometric factors and risks of IDC (n = 656) and ILC (n = 196) were evaluated using polytomous logistic regression. Earlier age at menarche, later age at menopause and obesity were more strongly associated with elevated risks of IDC than ILC. Alternatively, oral contraceptive use was associated with an increased risk of ILC but not IDC. Thus, the pattern of results that we observed suggest that factors influencing endogenous hormones and duration of ovarian function may be more strongly associated with IDC risk, while exogenous hormones may be more strongly associated with ILC risk.