Native American ancestry and breast cancer risk in Colombian and Mexican women: ruling out potential confounding through ancestry-informative markers.

BACKGROUND: Latin American and Hispanic women are less likely to develop breast cancer (BC) than women of European descent. Observational studies have found an inverse relationship between the individual proportion of Native American ancestry and BC risk. Here, we use ancestry-informative markers to rule out potential confounding of this relationship, estimating the confounder-free effect of Native American ancestry on BC risk. METHODS AND STUDY POPULATION: We used the informativeness for assignment measure to select robust instrumental variables for the individual proportion of Native American ancestry. We then conducted separate Mendelian randomization (MR) analyses based on 1401 Colombian women, most of them from the central Andean regions of Cundinamarca and Huila, and 1366 Mexican women from Mexico City, Monterrey and Veracruz, supplemented by sensitivity and stratified analyses. RESULTS: The proportion of Colombian Native American ancestry showed a putatively causal protective effect on BC risk (inverse variance-weighted odds ratio [OR] = 0.974 per 1% increase in ancestry proportion, 95% confidence interval [CI] 0.970-0.978, p = 3.1 × 10-40). The corresponding OR for Mexican Native American ancestry was 0.988 (95% CI 0.987-0.990, p = 1.4 × 10-44). Stratified analyses revealed a stronger association between Native American ancestry and familial BC (Colombian women: OR = 0.958, 95% CI 0.952-0.964; Mexican women: OR = 0.973, 95% CI 0.969-0.978), and stronger protective effects on oestrogen receptor (ER)-positive BC than on ER-negative and triple-negative BC. CONCLUSIONS: The present results point to an unconfounded protective effect of Native American ancestry on BC risk in both Colombian and Mexican women which appears to be stronger for familial and ER-positive BC. These findings provide a rationale for personalised prevention programmes that take genetic ancestry into account, as well as for future admixture mapping studies.

The effect of the number of biopsies on the delay in the time from the delivery of mammography results to breast cancer histopathological diagnosis.

PURPOSE: The delay in the time (in calendar days) from the delivery of mammography results to histopathological breast cancer (BC) diagnosis could be associated with more advanced clinical stages, a worse prognosis and higher mortality. Therefore, we assessed the association between the number of biopsies and the delay in the time (in calendar days) from the delivery of mammography results to histopathological BC. METHODS: A survey was performed on 563 women aged between 35 and 69 years with histopathologically confirmed BC who attended 11 Mexican hospitals. RESULTS: After adjusting for potential confounders, the odds of having a delay in the time (in calendar days) from the delivery of mammography results to histopathological BC diagnosis (≥ 60 days) among women with ≥ 3 biopsies were 2.99 times the odds of those who had only one biopsy (95% CI 1.35, 6.63). CONCLUSION: The number of biopsies should be considered as a predictor of the time delay between the delivery of the mammography result and the diagnostic result.

Inflammatory biomarkers and risk of breast cancer among young women in Latin America: a case-control study.

BACKGROUND: Breast cancer incidence is increasing rapidly in Latin America, with a higher proportion of cases among young women than in developed countries. Studies have linked inflammation to breast cancer development, but data is limited in premenopausal women, especially in Latin America. METHODS: We investigated the associations between serum biomarkers of chronic inflammation (interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), leptin, adiponectin) and risk of premenopausal breast cancer among 453 cases and 453 matched, population-based controls from Chile, Colombia, Costa Rica, and Mexico. Odds ratios (OR) were estimated using conditional logistic regression models. Analyses were stratified by size and hormonal receptor status of the tumors. RESULTS: IL-6 (ORper standard deviation (SD) = 1.33 (1.11-1.60)) and TNF-α (ORper SD = 1.32 (1.11-1.58)) were positively associated with breast cancer risk in fully adjusted models. Evidence of heterogeneity by estrogen receptor (ER) status was observed for IL-8 (P-homogeneity = 0.05), with a positive association in ER-negative tumors only. IL-8 (P-homogeneity = 0.06) and TNF-α (P-homogeneity = 0.003) were positively associated with risk in the largest tumors, while for leptin (P-homogeneity = 0.003) a positive association was observed for the smallest tumors only. CONCLUSIONS: The results of this study support the implication of chronic inflammation in breast cancer risk in young women in Latin America. Largest studies of prospective design are needed to confirm these findings in premenopausal women.

Patient and treatment delays among Mexican women with breast cancer before and after the Seguro Popular.

OBJECTIVE: To assess whether the Catastrophic Health Expenditures Fund (FPGC, Spanish acronym) was associated with delays in seeking medical care and in starting treatment. MATERIALS AND METHODS: We conducted a before and after cross-sectional study. We included 266 women with breast cancer (BC) diagnosis treated during the last three years before the hospitals received the FPGC and 309 wo-men treated in the following three years after the fund was received by the accredited hospitals. RESULTS: After adjusting for potential confounders, we found no association between the FPGC and delay in seeking medical care or between the FPGC and the treatment delay. CONCLUSIONS: The FPGC initiative reduced neither the delay in seeking breast cancer medical care for breast cancer nor the treatment delay.

Identification of novel common breast cancer risk variants at the 6q25 locus among Latinas.

BACKGROUND: Breast cancer is a partially heritable trait and genome-wide association studies (GWAS) have identified over 180 common genetic variants associated with breast cancer. We have previously performed breast cancer GWAS in Latinas and identified a strongly protective single nucleotide polymorphism (SNP) at 6q25, with the protective minor allele originating from indigenous American ancestry. Here we report on fine mapping of the 6q25 locus in an expanded sample of Latinas. METHODS: We performed GWAS in 2385 cases and 6416 controls who were either US Latinas or Mexican women. We replicated the top SNPs in 2412 cases and 1620 controls of US Latina, Mexican, and Colombian women. In addition, we validated the top novel variants in studies of African, Asian and European ancestry. In each dataset we used logistic regression models to test the association between SNPs and breast cancer risk and corrected for genetic ancestry using either principal components or genetic ancestry inferred from ancestry informative markers using a model-based approach. RESULTS: We identified a novel set of SNPs at the 6q25 locus associated with genome-wide levels of significance (p = 3.3 × 10- 8 - 6.0 × 10- 9) not in linkage disequilibrium (LD) with variants previously reported at this locus. These SNPs were in high LD (r2 > 0.9) with each other, with the top SNP, rs3778609, associated with breast cancer with an odds ratio (OR) and 95% confidence interval (95% CI) of 0.76 (0.70-0.84). In a replication in women of Latin American origin, we also observed a consistent effect (OR 0.88; 95% CI 0.78-0.99; p = 0.037). We also performed a meta-analysis of these SNPs in East Asians, African ancestry and European ancestry populations and also observed a consistent effect (rs3778609, OR 0.95; 95% CI 0.91-0.97; p = 0.0017). CONCLUSION: Our study adds to evidence about the importance of the 6q25 locus for breast cancer susceptibility. Our finding also highlights the utility of performing additional searches for genetic variants for breast cancer in non-European populations.

A Pooled Analysis of Breastfeeding and Breast Cancer Risk by Hormone Receptor Status in Parous Hispanic Women.

BACKGROUND: Data on breastfeeding and breast cancer risk are sparse and inconsistent for Hispanic women. METHODS: Pooling data for nearly 6,000 parous Hispanic women from four population-based studies conducted between 1995 and 2007 in the United States and Mexico, we examined the association of breastfeeding with risk of breast cancer overall and subtypes defined by estrogen receptor (ER) and progesterone receptor (PR) status, and the joint effects of breastfeeding, parity, and age at first birth. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression. RESULTS: Among parous Hispanic women, older age at first birth was associated with increased breast cancer risk, whereas parity was associated with reduced risk. These associations were found for hormone receptor positive (HR+) breast cancer only and limited to premenopausal women. Age at first birth and parity were not associated with risk of ER- and PR- breast cancer. Increasing duration of breastfeeding was associated with decreasing breast cancer risk (≥25 vs. 0 months: OR = 0.73; 95% CI = 0.60, 0.89; Ptrend = 0.03), with no heterogeneity by menopausal status or subtype. At each parity level, breastfeeding further reduced HR+ breast cancer risk. Additionally, breastfeeding attenuated the increase in risk of HR+ breast cancer associated with older age at first birth. CONCLUSIONS: Our findings suggest that breastfeeding is associated with reduced risk of both HR+ and ER- and PR- breast cancer among Hispanic women, as reported for other populations, and may attenuate the increased risk in women with a first pregnancy at older ages.

The Public Health Leadership and Implementation Academy for Noncommunicable Diseases.

PURPOSE AND OBJECTIVES: Low- and middle-income countries (LMICs) have a large burden of noncommunicable diseases and confront leadership capacity challenges and gaps in implementation of proven interventions. To address these issues, we designed the Public Health Leadership and Implementation Academy (PH-LEADER) for noncommunicable diseases. The objective of this program evaluation was to assess the quality and effectiveness of PH-LEADER. INTERVENTION APPROACH: PH-LEADER was directed at midcareer public health professionals, researchers, and government public health workers from LMICs who were involved in prevention and control of noncommunicable diseases. The 1-year program focused on building implementation research and leadership capacity to address noncommunicable diseases and included 3 complementary components: a 2-month online preparation period, a 2-week summer course in the United States, and a 9-month, in-country, mentored project. EVALUATION METHODS: Four trainee groups participated from 2013 through 2016. We collected demographic information on all trainees and monitored project and program outputs. Among the 2015 and 2016 trainees, we assessed program satisfaction and pre-post program changes in leadership practices and the perceived competence of trainees for performing implementation research. RESULTS: Ninety professionals (mean age 38.8 years; 57% male) from 12 countries were trained over 4 years. Of these trainees, 50% were from India and 29% from Mexico. Trainees developed 53 projects and 9 publications. Among 2015 and 2016 trainees who completed evaluation surveys (n = 46 of 55), we saw pre-post training improvements in the frequency with which they acted as role models (Cohen's d = 0.62, P <.001), inspired a shared vision (d = 0.43, P =.005), challenged current processes (d = 0.60, P <.001), enabled others to act (d = 0.51, P =.001), and encouraged others by recognizing or celebrating their contributions and accomplishments (d = 0.49, P =.002). Through short on-site evaluation forms (scale of 1-10), trainees rated summer course sessions as useful (mean, 7.5; SD = 0.2), with very good content (mean, 8.5; SD = 0.6) and delivered by very good professors (mean, 8.6; SD = 0.6), though they highlighted areas for improvement. IMPLICATIONS FOR PUBLIC HEALTH: The PH-LEADER program is a promising strategy to build implementation research and leadership capacity to address noncommunicable diseases in LMICs.

Project profile: a multicenter study on breast cancer in young women in Latin America (PRECAMA study).

OBJECTIVE: To describe the rationale and the methodology of a multicenter project to study the etiology of breast cancer in young Latin American women. MATERIALS AND METHODS: The International Agency for Research on Cancer has established an international collaborative population-based case-control study in four countries in Latin America: Chile, Colombia, Costa Rica, and Mexico (the PRECAMA study). Standardized methodologies were developed to collect information on reproductive variables, lifestyle, anthropometry, diet, clinical and pathological data, and biological specimens. The study will be extended to other countries in the region. CONCLUSIONS: PRECAMA is unique in its multidisciplinary approach that combines genetics, genomics, and metabolomics with lifestyle factors. Then data generated through this project will be instrumental to identify major risk factors for molecular subtypes of breast cancer in young women, which will be important for pre- vention and targeted screening programs in Latin America.

OBJETIVO: Describir la justificación y la metodología para el establecimiento de un proyecto multicéntrico sobre el cáncer de mama en mujeres jóvenes de América Latina. MATERIAL Y MÉTODOS: La Agencia Internacional para la Investigación del Cáncer (IARC) ha establecido un estudio colaborativo internacional de casos y controles con base poblacional en cuatro países de América Latina: Chile, Colombia, Costa Rica y México (el estudio PRECAMA). Se han desarrollado metodologías estandarizadas para recolectar información sobre variables reproductivas, estilos de vida, antropometría y dieta, datos clínicos y patológicos y muestras biológicas. CONCLUSIONES: PRECAMA es único en su enfoque multidisciplinario. Los datos generados a través de este proyecto serán fundamentales para identificar los principales factores de riesgo del cáncer de mama en mujeres jóvenes. Los hallazgos serán relevantes para la prevención y los programas de detección oportuna en América Latina, con beneficios clínicos inmediatos.

Thyroid hormones and breast cancer association according to menopausal status and body mass index.

BACKGROUND: Thyroxine (T4) has been positively associated with tumor cell proliferation, while the effect of triiodothyronine (T3) on cell proliferation has not been well-established because it differs according to the type of cell line used. In Mexico, it has been reported that 14.5% of adult women have some type of thyroid dysfunction and abnormalities in thyroid function tests have been observed in a variety of non-thyroidal illnesses, including breast cancer (BC). These abnormalities might change with body mass index (BMI) because thyroid hormones are involved in the regulation of various metabolic pathways and probably by menopausal status because obesity has been negatively associated with BC in premenopausal women and has been positively associated with BC in postmenopausal women. METHODS: To assess the association between serum thyroid hormone concentration (T4 and T3) and BC and the influence of obesity as an effect modifier of this relationship in premenopausal and postmenopausal women, we measured serum thyroid hormone and thyroid antibody levels in 682 patients with incident breast cancer (cases) and 731 controls, who participated in a population-based case-control study performed from 2004 to 2007 in three states of Mexico. We tested the association of total T4 (TT4) and total T3 (TT3) stratifying by menopausal status and body mass index (BMI), and adjusted for other health and demographic risk factors using logistic regressions models. RESULTS: Higher serum total T4 (TT4) concentrations were associated with BC in both premenopausal (odds ratio (OR) per standard deviation = 5.98, 95% CI 3.01-11.90) and postmenopausal women (OR per standard deviation = 2.81, 95% CI 2.17-3.65). In premenopausal women, the effect of TT4 decreased as BMI increased while the opposite was observed in postmenopausal women. The significance of the effect modification was marginal (p = 0.059) in postmenopausal women and was not significant in premenopausal women (p = 0.22). Lower TT3 concentrations were associated with BC in both premenopausal and postmenopausal women and no effect modification was observed. CONCLUSIONS: There is a strong association between BC and serum concentrations of TT3 and TT4; this needs to be further investigated to understand why it happens and how important it is to consider these alterations in treatment.

Association between serum phospholipid fatty acid levels and adiposity in Mexican women.

Fatty acids (FAs) have been postulated to impact adiposity, but few epidemiological studies addressing this hypothesis have been conducted. This study investigated the association between serum phospholipid FAs (S-PLFAs) and indicators of obesity. BMI and waist-to-hip ratio (WHR) were collected from 372 healthy Mexican women included as controls in a case-control study. S-PLFA percentages were determined through gas chromatography. Desaturation indices, SCD-16, SCD-18, FA desaturase (FADS)1, and FADS2, biomarkers of endogenous metabolism, were proxied respectively as 16:1n-7/16:0, 18:1n-9/18:0, 20:4n-6/20:3n-6, and 22:6n-3/20:5n-3. Multiple linear regressions adjusted for relevant confounders and corrected for multiple testing were conducted to determine the association between S-PLFA, desaturation indices, and indicators of adiposity. SCD-16 (ß = 0.034, P = 0.001, q = 0.014), palmitoleic acid (ß = 0.031, P = 0.001, q = 0.014), and dihomo-γ-linolenic acid (ß = 0.043, P = 0.000, q = 0.0002) were positively associated with BMI. Total n-6 PUFAs (ß = 1.497, P = 0.047, q = 0.22) and the ratio of n-6/n-3 PUFAs (ß = 0.034, P = 0.040, q = 0.19) were positively associated with WHR, while odd-chain FAs (pentadecanoic and heptadecanoic acid) showed negative associations with all the adiposity indicators. In conclusion, increased endogenous synthesis of palmitoleic acid and a high n-6/n-3 ratio are associated with increased adiposity, while odd-chain FAs are associated with decreased adiposity. Further studies are needed to determine the potential causality behind these associations.

Economic and disease burden of breast cancer associated with suboptimal breastfeeding practices in Mexico.

PURPOSE: Exclusive breastfeeding and longer breastfeeding reduce women's breast cancer risk but Mexico has one of the lowest breastfeeding rates worldwide. We estimated the lifetime economic and disease burden of breast cancer in Mexico if 95% of parous women breastfeed each child exclusively for 6 months and continue breastfeeding for over a year. METHODS: We used a static microsimulation model with a cost-of-illness approach to simulate a cohort of Mexican women. We estimated breast cancer incidence, premature mortality, disability-adjusted life years (DALYs), medical costs, and income losses due to breast cancer and extrapolated the results to 1.116 million Mexican women of age 15 in 2012. Costs were expressed in 2015 US dollars and discounted at a 3% annual rate. RESULTS: We estimated that 2,186 premature deaths (95% CI 2,123-2,248), 9,936 breast cancer cases (95% CI 9,651-10,220), 45,109 DALYs (95% CI 43,000-47,217), and $245 million USD (95% CI 234-256) in medical costs and income losses owing to breast cancer could be saved over a cohort's lifetime. Medical costs account for 80% of the economic burden; income losses and opportunity costs for caregivers account for 15 and 5%, respectively. CONCLUSIONS: In Mexico, the burden of breast cancer due to suboptimal breastfeeding in women is high in terms of morbidity, premature mortality, and the economic costs for the health sector and society.

The Epidemiological Challenges of Breast Cancer among Premenopausal Women in Limited Resource Settings.

Breast cancer is the most common malignant tumor among women of reproductive age and is also the most costly according to European reports. In this context, the aim of the present review is to identify factors that make breast cancer in premenopausal women an epidemiological challenge in developing countries. Epidemiological aspects of breast cancer, including risk factors, early detection methods, and treatment, are addressed. Breast cancer in premenopausal women should be included in the political and strategic agendas in developing countries to direct the necessary resources for prevention, detection, and control.

Red meat, poultry, and fish intake and breast cancer risk among Hispanic and Non-Hispanic white women: The Breast Cancer Health Disparities Study.

PURPOSE: There is suggestive but limited evidence for a relationship between meat intake and breast cancer (BC) risk. Few studies included Hispanic women. We investigated the association between meats and fish intake and BC risk among Hispanic and NHW women. METHODS: The study included NHW (1,982 cases and 2,218 controls) and the US Hispanics (1,777 cases and 2,218 controls) from two population-based case-control studies. Analyses considered menopausal status and percent Native American ancestry. We estimated pooled ORs combining harmonized data from both studies, and study- and race-/ethnicity-specific ORs that were combined using fixed or random effects models, depending on heterogeneity levels. RESULTS: When comparing highest versus lowest tertile of intake, among NHW we observed an association between tuna intake and BC risk (pooled OR 1.25; 95 % CI 1.05-1.50; trend p = 0.006). Among Hispanics, we observed an association between BC risk and processed meat intake (pooled OR 1.42; 95% CI 1.18-1.71; trend p < 0.001), and between white meat (OR 0.80; 95% CI 0.67-0.95; trend p = 0.01) and BC risk, driven by poultry. All these findings were supported by meta-analysis using fixed or random effect models and were restricted to estrogen receptor-positive tumors. Processed meats and poultry were not associated with BC risk among NHW women; red meat and fish were not associated with BC risk in either race/ethnic groups. CONCLUSIONS: Our results suggest the presence of ethnic differences in associations between meat and BC risk that may contribute to BC disparities.

Hospitalization and mortality in Mexico due to breast cancer since its inclusion in the catastrophic expenditures scheme.

OBJECTIVE: To compare trends in hospital discharges and mortality due to breast cancer (BC) in Mexico from 2004 to 2012 by insurance condition before and after incorporating BC comprehensive treatment into the System of Social Protection in Health (Sistema de Protrección Social en Salud, SPSS) in 2007. MATERIALS AND METHODS: Data on BC hospital discharges and mortality reported in women aged 25 years and over were obtained from the National Health Information System. Mortality rates were adjusted by age and state. RESULTS: At the national level, a growing tendency in hospital discharges was observed, mainly for women without social security, while mortality rate remained constant. Mortality rates by state show that lower marginalization index corresponded to higher mortality. CONCLUSIONS: A differential behavior was observed among women according to insurance condition, partly due to the inclusion of BC treatment in the SPSS.

Effect of care-delivery delay on the survival of Mexican women with breast cancer.

OBJECTIVE: To estimate the effect of care-delivery delays on survival among women with breast cancer. MATERIALS AND METHODS: A retrospective analysis of 854 women attending 11 hospitals from 2007-2009 was carried out. Kaplan-Meier estimators and a Cox proportional-risk model were employed. RESULTS: A total of 10.5% of cases were diagnosed in stage I. 82% of sampled women delayed care for more than 67 days between noticing a symptom and initiating treatment. The median time from receipt of results of the mammography to biopsy was 31 days (IQR 14-56). Compared with those who were in quartile I (Q1), survival was lower among those in Q3 and Q4 (HR=1.68, 95%CI 0.94-3.00; HR=1.76, 95% CI 1.04-2.98, respectively). CONCLUSIONS: To increase survival, it is suggested that the time between receipt of the mammography results and diagnostic biopsy be reduced.

Associations between ALOX, COX, and CRP polymorphisms and breast cancer among Hispanic and non-Hispanic white women: The breast cancer health disparities study.

Chronic inflammation is suggested to be associated with specific cancer sites, including breast cancer. Recent research has focused on the roles of genes involved in the leukotriene/lipoxygenase and prostaglandin/cyclooxygenase pathways in breast cancer etiology. We hypothesized that genes in ALOX/COX pathways and CRP polymorphisms would be associated with breast cancer risk and mortality in our sample of Hispanic/Native American (NA) (1430 cases, 1599 controls) and non-Hispanic white (NHW) (2093 cases, 2610 controls) women. A total of 104 Ancestral Informative Markers was used to distinguish European and NA ancestry. The adaptive rank truncated product (ARTP) method was used to determine the significance of associations for each gene and the inflammation pathway with breast cancer risk and by NA ancestry. Overall, the pathway was associated with breast cancer risk (PARTP = 0.01). Two-way interactions with NA ancestry (P(adj) < 0.05) were observed for ALOX12 (rs2292350, rs2271316) and PTGS1 (rs10306194). We observed increases in breast cancer risk in stratified analyses by tertiles of polyunsaturated fat intake for ALOX12 polymorphisms; the largest increase in risk was among women in the highest tertile with ALOX12 rs9904779CC (Odds Ratio (OR), 1.49; 95% Confidence Interval (CI) 1.14-1.94, P(adj) = 0.01). In a sub-analysis stratified by NSAIDs use, two-way interactions with NSAIDs use were found for ALOX12 rs9904779 (P(adj) = 0.02), rs434473 (P(adj ) = 0.02), and rs1126667 (P(adj) = 0.01); ORs for ALOX12 polymorphisms ranged from 1.55 to 1.64 among regular users. Associations were not observed with breast cancer mortality. These findings could support advances in the discovery of new pathways related to inflammation for breast cancer treatment.

Endogenous hormones, inflammation, and body size in premenopausal Mexican women: results from the Mexican Teachers' Cohort (MTC, ESMaestras).

PURPOSE: Obesity is a major risk factor for several cancers, including female cancers. Endogenous hormones and inflammatory factors may mediate the association between anthropometric measures and cancer risk, although these associations have been studied mainly in Caucasians. The aim of the current study was to explore the association of circulating hormones, adipokines, and inflammatory factors with obesity and overweight in premenopausal Mexican women. METHODS: We conducted a cross-sectional analysis of 504 premenopausal women from the large Mexican Teachers' Cohort (MTC, ESMaestras) study to determine the association of insulin-like growth factor I (IGF-I), its major circulating binding protein (IGFBP-3), leptin, adiponectin, C-peptide, and C-reactive protein with comprehensive measures of body size. Biomarkers were measured by immunoassays. Multivariate regression analyses were performed to compare geometric mean biomarker concentrations with measured markers of body size and adiposity. RESULTS: Mean IGF-I and IGFBP-3 concentrations significantly increased with increasing height and leg length. Concentrations of IGF-I, adiponectin, and the IGF-I/IGFBP-3 ratio strongly decreased with increasing BMI, weight, waist and hip circumferences, waist-to-hip ratio (WHpR), and waist-to-height ratio (WHtR), while CRP, leptin, C-peptide concentrations, and the leptin/adiponectin ratio strongly increased. Adiponectin and the leptin/adiponectin ratio remained significantly related to measures of central adiposity (waist circumference, WHpR, and WHtR) after adjustment by body mass index. CONCLUSIONS: The results of our study suggest a strong relation between biomarkers and body size in this study population and suggest that different fat depots may have different metabolic properties.

Dietary Carbohydrate, Glycemic Index, Glycemic Load, and Breast Cancer Risk Among Mexican Women.

BACKGROUND: Very few studies have focused on the relationship among dietary carbohydrates, glycemic index (GI), glycemic load (GL), and breast cancer risk in Latin American women. Our objective was to assess the associations among dietary carbohydrate, GI, GL, and risk of breast cancer, and to further investigate these associations by levels of overweight/obesity and physical activity. METHODS: We used data from a Mexican population-based case-control study. We recruited a 1,000 women with incident breast cancer and 1,074 matched control women ages 35 to 69 years between 2004 and 2007. We used conditional logistic regression models and energy-adjusted carbohydrates, GI, and GL using the residual method. RESULTS: Total carbohydrate intake was associated with an increased risk of breast cancer among premenopausal women. The odds ratio in the highest versus the lowest quartile was 1.3 (95% confidence interval = 1.0, 1.7; P trend = 0.03). In stratified analyses by body mass index (BMI), the positive association between carbohydrate and risk of premenopausal breast cancer was only observed among overweight women. The odds ratio comparing the top with the bottom quartile was 1.9 (95% confidence interval = 1.2, 3.0; P trend = 0.01) among women with BMI ≥ 25 kg/m. No association was observed among women with BMI < 25 kg/m. CONCLUSIONS: Our findings suggest that high carbohydrate diets are associated with an increased risk of breast cancer among premenopausal Mexican women.

Radiographers supporting radiologists in the interpretation of screening mammography: a viable strategy to meet the shortage in the number of radiologists.

BACKGROUND: An alternative approach to the traditional model of radiologists interpreting screening mammography is necessary due to the shortage of radiologists to interpret screening mammograms in many countries. METHODS: We evaluated the performance of 15 Mexican radiographers, also known as radiologic technologists, in the interpretation of screening mammography after a 6 months training period in a screening setting. Fifteen radiographers received 6 months standardized training with radiologists in the interpretation of screening mammography using the Breast Imaging Reporting and Data System (BI-RADS) system. A challenging test set of 110 cases developed by the Breast Cancer Surveillance Consortium was used to evaluate their performance. We estimated sensitivity, specificity, false positive rates, likelihood ratio of a positive test (LR+) and the area under the subject-specific Receiver Operating Characteristic (ROC) curve (AUC) for diagnostic accuracy. A mathematical model simulating the consequences in costs and performance of two hypothetical scenarios compared to the status quo in which a radiologist reads all screening mammograms was also performed. RESULTS: Radiographer's sensitivity was comparable to the sensitivity scores achieved by U.S. radiologists who took the test but their false-positive rate was higher. Median sensitivity was 73.3 % (Interquartile range, IQR: 46.7-86.7 %) and the median false positive rate was 49.5 % (IQR: 34.7-57.9 %). The median LR+ was 1.4 (IQR: 1.3-1.7 %) and the median AUC was 0.6 (IQR: 0.6-0.7). A scenario in which a radiographer reads all mammograms first, and a radiologist reads only those that were difficult for the radiographer, was more cost-effective than a scenario in which either the radiographer or radiologist reads all mammograms. CONCLUSIONS: Given the comparable sensitivity achieved by Mexican radiographers and U.S. radiologists on a test set, screening mammography interpretation by radiographers appears to be a possible adjunct to radiologists in countries with shortages of radiologists. Further studies are required to assess the effectiveness of different training programs in order to obtain acceptable screening accuracy, as well as the best approaches for the use of non-physician readers to interpret screening mammography.

MAPK genes interact with diet and lifestyle factors to alter risk of breast cancer: the Breast Cancer Health Disparities Study.

Mitogen-activated protein kinases (MAPK) are integration points for multiple biochemical signals. We evaluated 13 MAPK genes with breast cancer risk and determined if diet and lifestyle factors mediated risk. Data from 3 population-based case-control studies conducted in Southwestern United States, California, and Mexico included 4183 controls and 3592 cases. Percent Indigenous American (IA) ancestry was determined from 104 ancestry informative markers. The adaptive rank truncated product (ARTP) was used to determine the significance of each gene and the pathway with breast cancer risk, by menopausal status, genetic ancestry level, and estrogen receptor (ER)/progesterone receptor (PR) strata. MAP3K9 was associated with breast cancer overall (P(ARTP) = 0.02) with strongest association among women with the highest IA ancestry (P(ARTP) = 0.04). Several SNPs in MAP3K9 were associated with ER+/PR+ tumors and interacted with dietary oxidative balance score (DOBS), dietary folate, body mass index (BMI), alcohol consumption, cigarette smoking, and a history of diabetes. DUSP4 and MAPK8 interacted with calories to alter breast cancer risk; MAPK1 interacted with DOBS, dietary fiber, folate, and BMI; MAP3K2 interacted with dietary fat; and MAPK14 interacted with dietary folate and BMI. The patterns of association across diet and lifestyle factors with similar biological properties for the same SNPs within genes provide support for associations.