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Abstract Background Elevated mammographic density (MD) for a woman’s age and body mass index (BMI) is an established breast cancer risk factor. The relationship of parity, age at first birth, and breastfeeding with MD is less clear. We examined the associations of these factors with MD within the International Consortium of Mammographic Density (ICMD). Methods ICMD is a consortium of 27 studies with pooled individual-level epidemiological and MD data from 11,755 women without breast cancer aged 35–85 years from 22 countries, capturing 40 country-& ethnicity-specific population groups. MD was measured using the area-based tool Cumulus. Meta-analyses across population groups and pooled analyses were used to examine linear regression associations of square-root (√) transformed MD measures (percent MD (PMD), dense area (DA), and non-dense area (NDA)) with parity, age at first birth, ever/never breastfed and lifetime breastfeeding duration. Models were adjusted for age at mammogram, age at menarche, BMI, menopausal status, use of hormone replacement therapy, calibration method, mammogram view and reader, and parity and age at first birth when not the association of interest. Results Among 10,988 women included in these analyses, 90.1% (n = 9,895) were parous, of whom 13% (n = 1,286) had ≥ five births. The mean age at first birth was 24.3 years (Standard deviation = 5.1). Increasing parity (per birth) was inversely associated with √PMD (β: − 0.05, 95% confidence interval (CI): − 0.07, − 0.03) and √DA (β: − 0.08, 95% CI: − 0.12, − 0.05) with this trend evident until at least nine births. Women who were older at first birth (per five-year increase) had higher √PMD (β:0.06, 95% CI:0.03, 0.10) and √DA (β:0.06, 95% CI:0.02, 0.10), and lower √NDA (β: − 0.06, 95% CI: − 0.11, − 0.01). In stratified analyses, this association was only evident in women who were post-menopausal at MD assessment. Among parous women, no associations were found between ever/never breastfed or lifetime breastfeeding duration (per six-month increase) and √MD. Conclusions Associations with higher parity and older age at first birth with √MD were consistent with the direction of their respective associations with breast cancer risk. Further research is needed to understand reproductive factor-related differences in the composition of breast tissue and their associations with breast cancer risk.

Abstract In 2011, Chile added 12 mandatory extra weeks of maternity leave (ML). In January 2015, a pay-for-performance (P4P) strategy was included in the primary healthcare system, incorporating exclusive breastfeeding (EBF) promotion actions. The COVID-19 pandemic led to healthcare access difficulties and augmented household workloads. Our aim was to evaluate the effect of a 24-week ML, the P4P strategy, and COVID-19 on EBF prevalence, at 3 and 6 months in Chile. Aggregated EBF prevalence data from public healthcare users nationwide (80% of the Chilean population) was collected by month. Interrupted time series analyses were used to quantify changes in EBF trends from 2009 to 2020. The heterogeneity of EBF changes was assessed by urban/setting and across geographic settings. We found no effect of ML on EBF; the P4P strategy increased EBF at 3 months by 3.1% and 5.7% at 6 months. COVID-19 reduced EBF at 3 months by − 4.5%. Geographical heterogeneity in the impact of the two policies and COVID-19 on EBF was identified. The null effect of ML on EBF in the public healthcare system could be explained by low access from public healthcare users to ML (20% had access to ML) and by an insufficient ML duration (five and a half months). The negative impact of COVID-19 on EBF should alert policy makers about the crisis's effect on health promotion activities.

Abstract 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.

Abstract Background Early age at menarche and tall stature are associated with increased breast cancer risk. We examined whether these associations were also positively associated with mammographic density, a strong marker of breast cancer risk. Methods Participants were 10,681 breast-cancer-free women from 22 countries in the International Consortium of Mammographic Density, each with centrally assessed mammographic density and a common set of epidemiologic data. Study periods for the 27 studies ranged from 1987 to 2014. Multi-level linear regression models estimated changes in square-root per cent density (√PD) and dense area (√DA) associated with age at menarche and adult height in pooled analyses and population-specific meta-analyses. Models were adjusted for age at mammogram, body mass index, menopausal status, hormone therapy use, mammography view and type, mammographic density assessor, parity and height/age at menarche. Results In pooled analyses, later age at menarche was associated with higher per cent density (β √PD = 0.023 SE = 0.008, P = 0.003) and larger dense area (β √DA = 0.032 SE = 0.010, P = 0.002). Taller women had larger dense area (β √DA = 0.069 SE = 0.028, P = 0.012) and higher per cent density (β √PD = 0.044, SE = 0.023, P = 0.054), although the observed effect on per cent density depended upon the adjustment used for body size. Similar overall effect estimates were observed in meta-analyses across population groups. Conclusions In one of the largest international studies to date, later age at menarche was positively associated with mammographic density. This is in contrast to its association with breast cancer risk, providing little evidence of mediation. Increased height was also positively associated with mammographic density, particularly dense area. These results suggest a complex relationship between growth and development, mammographic density and breast cancer risk. Future studies should evaluate the potential mediation of the breast cancer effects of taller stature through absolute breast density.

Introduction Healthcare fragmentation, a main cause for delay in cancer diagnosis and treatment, contributes to high mortality in Latin America (LA), particularly among disadvantaged populations. This research focuses on integrated care interventions, which have been limitedly implemented in the region. The objective is to evaluate the contextual effectiveness of scaling-up an integrated care intervention to improve early diagnosis of frequent cancers in healthcare networks of Chile, Colombia and Ecuador.Methods and analysis This research is two pronged: (A) quasi-experimental design (controlled before and after) with an intervention and a control healthcare network in each LA country, using an implementation-effectiveness hybrid approach to assess the intervention process, effectiveness and costs; and (B) case study design to analyse access to diagnosis of most frequent cancers. Focusing on the most vulnerable socioeconomic population, it develops in four phases: (1) analysis of delays and barriers to early diagnosis (baseline); (2) intervention adaptation and implementation (primary care training, fast-track referral pathway and patient information); (3) intracountry evaluation of intervention and (4) cross-country analysis. Baseline and evaluation studies adopt mixed-methods qualitative (semistructured individual interviews) and quantitative (patient questionnaire survey) methods. For the latter, a sample size of 174 patients with cancer diagnosis per healthcare network and year was calculated to detect a proportions difference of 15%, before and after intervention (α=0.05; β=0.2) in a two-sided test. A participatory approach will be used to tailor the intervention to each context, led by a local steering committee (professionals, managers, policy makers, patients and researchers).Ethics and dissemination This study complies with international and national legal stipulations on ethics. It was approved by each country’s ethical committee and informed consent will be obtained from participants. Besides the coproduction of knowledge with key stakeholders, it will be disseminated through strategies such as policy briefs, workshops, e-tools and scientific papers.

BackgroundIn Latin America (LA), there is a high incidence rate of breast cancer (BC) in premenopausal women, and the genomic features of these BC remain unknown. Here, we aim to characterize the molecular features of BC in young LA women within the framework of the PRECAMA study, a multicenter population-based case-control study of BC in premenopausal women.MethodsPathological tumor tissues were collected from incident cases from four LA countries. Immunohistochemistry (IHC) was performed centrally for ER, PR, HER2, Ki67, EGFR, CK5/6, and p53 protein markers. Targeted deep sequencing was done on genomic DNA extracted from formalin-fixed, paraffin-embedded tumor tissues and their paired blood samples to screen for somatic mutations in eight genes frequently mutated in BC. A subset of samples was analyzed by exome sequencing to identify somatic mutational signatures.ResultsThe majority of cases were positive for ER or PR (168/233; 72%), and 21% were triple-negative (TN), mainly of basal type. Most tumors were positive for Ki67 (189/233; 81%). In 126 sequenced cases, TP53 and PIK3CA were the most frequently mutated genes (32.5% and 21.4%, respectively), followed by AKT1 (9.5%). TP53 mutations were more frequent in HER2-enriched and TN IHC subtypes, whereas PIK3CA/AKT1 mutations were more frequent in ER-positive tumors, as expected. Interestingly, a higher proportion of G:C>T:A mutations was observed in TP53 in PRECAMA cases compared with TCGA and METABRIC BC series (27% vs 14%). Exome-wide mutational patterns in 10 TN cases revealed alterations in signal transduction pathways and major contributions of mutational signatures caused by altered DNA repair pathways.ConclusionsThese pilot results on PRECAMA tumors give a preview of the molecular features of premenopausal BC in LA. Although the overall mutation burden was as expected from data in other populations, mutational patterns observed in TP53 and exome-wide suggested possible differences in mutagenic processes giving rise to these tumors compared with other populations. Further -omics analyses of a larger number of cases in the near future will enable the investigation of relationships between these molecular features and risk factors.

BackgroundMammographic density (MD) is one of the strongest breast cancer risk factors. Its age-related characteristics have been studied in women in western countries, but whether these associations apply to women worldwide is not known.Methods and findingsWe examined cross-sectional differences in MD by age and menopausal status in over 11,000 breast-cancer-free women aged 35-85 years, from 40 ethnicity- and location-specific population groups across 22 countries in the International Consortium on Mammographic Density (ICMD). MD was read centrally using a quantitative method (Cumulus) and its square-root metrics were analysed using meta-analysis of group-level estimates and linear regression models of pooled data, adjusted for body mass index, reproductive factors, mammogram view, image type, and reader. In all, 4,534 women were premenopausal, and 6,481 postmenopausal, at the time of mammography. A large age-adjusted difference in percent MD (PD) between post- and premenopausal women was apparent (-0.46 cm [95% CI: -0.53, -0.39]) and appeared greater in women with lower breast cancer risk profiles; variation across population groups due to heterogeneity (I2) was 16.5%. Among premenopausal women, the √PD difference per 10-year increase in age was -0.24 cm (95% CI: -0.34, -0.14; I2 = 30%), reflecting a compositional change (lower dense area and higher non-dense area, with no difference in breast area). In postmenopausal women, the corresponding difference in √PD (-0.38 cm [95% CI: -0.44, -0.33]; I2 = 30%) was additionally driven by increasing breast area. The study is limited by different mammography systems and its cross-sectional rather than longitudinal nature.ConclusionsDeclines in MD with increasing age are present premenopausally, continue postmenopausally, and are most pronounced over the menopausal transition. These effects were highly consistent across diverse groups of women worldwide, suggesting that they result from an intrinsic biological, likely hormonal, mechanism common to women. If cumulative breast density is a key determinant of breast cancer risk, younger ages may be the more critical periods for lifestyle modifications aimed at breast density and breast cancer risk reduction.

Abstract Background Breast density (BD) is a strong risk factor for breast cancer. Little is known about how BD develops during puberty. Understanding BD trajectories during puberty and its determinants could be crucial for promoting preventive actions against breast cancer (BC) at early ages. The objective of this research is to characterize % fibroglandular volume (%FGV), absolute fibroglandular volume (AFGV), and breast volume (BV) at different breast Tanner stages until 4-year post menarche in a Latino cohort and to assess determinants of high %FGV and AFGV during puberty and in a fully mature breast. Methods This is a longitudinal follow-up of 509 girls from low-middle socioeconomic status of the Southeast area of Santiago, recruited at a mean age of 3.5 years. The inclusion criteria were singleton birth born, birthweight between 2500 and 4500 g with no medical or mental disorder. A trained dietitian measured weight and height since 3.5 years old and sexual maturation from 8 years old (breast Tanner stages and age at menarche onset). Using standardized methods, BD was measured using dual-energy X-ray absorptiometry (DXA) in various developmental periods (breast Tanner stage B1 until 4 years after menarche onset). Results In the 509 girls, we collected 1,442 breast DXA scans; the mean age at Tanner B4 was 11.3 years. %FGV increased across breast Tanner stages and peaked 250 days after menarche. AFGV and BV peaked 2 years after menarche onset. Girls in the highest quartiles of %FGV, AFGV, and BV at Tanner B4 and B5 before menarche onset had the highest values thereafter until 4 years after menarche onset. The most important determinants of %FGV and AFGV variability were BMI z-score (R2 = 44%) and time since menarche (R2 = 42%), respectively. Conclusion We characterize the breast development during puberty, a critical window of susceptibility. Although the onset of menarche is a key milestone for breast development, we observed that girls in the highest quartiles of %FGV and AFGV tracked in that group afterwards. Following these participants in adulthood would be of interest to understand the changes in breast composition during this period and its potential link with BC risk.

Abstract Objective: To provide local policymakers with a guideline of potential actions to prevent the high consumption of Non-Nutritive Sweeteners (NNS) among children and adolescents observed in Chile, given the potential health problems related to NNS intake. Design: The Delphi method was used for the evaluation of twenty-one recommendations to decrease the intake of NNS in paediatric population, with the participation of a panel of relevant actors. Setting: The proposed recommendations were developed by the research team using the NOURISHING framework; potential actions were based on the increase in the use and intake of NNS by Chilean children, current local food regulations, recommendations of health organisations and foreign policy experiences. Participants: Twenty-five relevant actors related to NNS, nutrition, food technology and paediatrics (out of thirty-nine invitations made to scholars, professional institutions and civil society’s organisations) participated in the Delphi study. Results: A consensus was reached on nine recommendations regarding relevance and feasibility to be part of the guideline. Recommendations involved measures mostly related to improving the delivery of information (food content and potential health effects of NNS), supporting the generation of more evidence of NNS health effects and substitutes, and marketing restrictions when targeted to children. Conclusions: The process produced a nine-action guideline to reduce the excessive NNS consumption among Chilean children and adolescents. Developed through a consensus-driven approach among key stakeholders, this guideline provides policymakers with a framework to adopt a precautionary stance, particularly concerning vulnerable populations, given the currently inconclusive evidence on the long-term health effects of NNS consumption.

IntroductionFood access is associated with dietary quality; however, people living in similar physical environments can have different food access profiles. Domestic environments may also influence how food access relates to dietary quality. We studied food access profiles of 999 low-middle income Chilean families with children during the COVID-19 lockdown and how these profiles relate to dietary quality; secondarily, we also explore the role of the domestic environment in this relationship.Materials and methodsParticipants of two longitudinal studies conducted in the southeast of Santiago, Chile, answered online surveys at the beginning and end of the COVID-19 pandemic lockdown. Food access profiles were developed by a latent class analysis considering food outlets and government food transfers. Children's dietary quality was estimated by self-reported compliance with the Chilean Dietary Guidelines of Americans (DGA) and daily ultra-processed food (UPF) consumption. Logistic and linear regressions were used to assess the association between food access profiles and dietary quality. Domestic environment data (i.e., the sex of the person who buys food and cooks, meal frequency, cooking skills, etc.) were incorporated in the models to assess their influence on the relationship between food access and dietary quality.ResultsWe have categorized three food access profiles: Classic (70.2%), Multiple (17.9%), and Supermarket-Restaurant (11.9%). Households led by women are concentrated in the Multiple profile, while families from higher income or education levels are focused on the Supermarket-Restaurant profile. On average, children presented poor dietary quality, with a high daily UPF consumption (median = 4.4; IQR: 3) and low compliance with national DGA recommendations (median = 1.2; IQR: 2). Except for the fish recommendation (OR = 1.77, 95% CI:1.00–3.12; p: 0.048 for the Supermarket-Restaurant profile), the food access profiles were poorly associated with children's dietary quality. However, further analyses showed that domestic environment variables related to routine and time use influenced the association between food access profiles and dietary quality.ConclusionIn a sample of low-middle income Chilean families, we identified three different food access profiles that presented a socioeconomic gradient; however, these profiles did not significantly explain children's dietary quality. Studies diving deeper into household dynamics might give us some clues on intra-household behaviors and roles that could be influencing how food access relates to dietary quality.

Abstract Community-acquired pneumonia (CAP) is a worldwide leading cause of death. Recognized risk factors in some severe cases have not been identified. Lymphocytopenia has been frequently described in CAP. Since IL-7, membrane-bound receptor (IL7Rα;CD127) and soluble IL7Rα (sIL7R) are critical in lymphocytes homeostasis, in this work we aimed to evaluate the involvement of the IL-7/IL7Rα axis in the severity of adult CAP, since it has not been explored. The IL7Rα SNPs rs6897932, rs987106, and rs3194051 SNPs in IL7α were genotyped, the systemic expression of the IL7R gene, sIL7R, IL-7, and levels of peripheral IL7Rα+ T lymphocytes were quantified in 202 hospitalized CAP cases. rs3194051GG was more frequent in non-survivors than in survivors; rs987106TT was more frequent and rs3194051AA less frequent in patients at intensive care unit (ICU) than in those not admitted to ICU. IL7Rα gene expression was lower in non-survivors than in survivors, and in severe than in mild cases. CD3+CD127+ lymphocytes were lower in severe than in mild cases; in non-survivors than in survivors and in ICU than in non- ICU admitted cases. sIL7Rα plasmatic levels were higher in non-survivors than in survivors, and in severe than in mild cases. rs6897932CC, rs987106AA and rs3194051GG carriers showed the highest while rs6897932TT showed the lowest sIL7Rα levels. The AUC of sIL7Rα levels predicting 30-day mortality was 0.71. Plasma IL-7 levels were lower in ICU-admitted than in not ICU-admitted and in non-survivors than in survivors. No additional association was detected. In conclusion, rs3194051GG and rs987106TT IL7R genotypes were associated with a poorer prognosis. A significant association between sIL7R levels and SNPs of the IL7R gene is described for the first time in adult CAP. Increased plasmatic sIL7R could contribute to identifying adult CAP cases at risk of death.

BackgroundPregnancy is a critical developmental window in which optimal maternal nutrition and health are key for pregnancy and infant development. The COVID-19 pandemic is considered as a “natural experiment” in which maternal and infant nutrition and health challenges were faced especially in developing countries. Therefore, understanding the health consequences for mothers and infants living in the COVID-19 era is key to revisit public health measures focused on maternal and infant health. The current work aims to describe the design, methods, and descriptive information at recruitment and preliminary findings of the Chilean Maternal & Infant Cohort Study II (CHiMINCs-II) cohort.MethodsThe CHiMINCs-II is an ongoing cohort that is part of the Chilean Maternal and Infant Nutrition Observatory of the South-East area of Santiago, Chile. In total, 1954 pregnant women beneficiaries of the public health systems and their offspring were recruited before 15 weeks of gestation and are followed across pregnancy (

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. Conclusion. PRECAMA is unique in its multidisciplinary approach that combines genet­ics, genomics, and metabolomics with lifestyle factors. The 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 pre­vention and targeted screening programs in Latin America.

Abstract Background Front-of package (FoP) nutrition labels are an option to guide consumer’s decision at the point of food purchase. Chile was the first country worldwide to implement a FoP warning label and thereafter several countries have followed this model. The objective of this study is to describe the process of development of the Chilean FoP warning label. Methods A stepwise study was conducted including literature review, qualitative phase (lay audience & expert group meetings) and quantitative phase in women/adolescents from low-middle-socioeconomic status neighborhoods, Santiago, Chile (2 sub-studies, using point-of-sale questionnaires). Outcomes were prototype visualization, ease of understanding, and ability to modify purchase behavior. Results The literature review and qualitative phase provided information on general text (e.g. short wording) and design characteristics (e.g. use of a logo, use of red or black colors); based on these characteristics 15 prototypes were created and quantitatively tested. In the first survey, a black-&-white stop sign and a black-&-white hand were preselected; in the second survey, the stop sign stating ‘Excess of ’ had significantly better performance than the hand in terms of visualization, intention to purchase, and ability to modify intended purchase. Due to legal reasons the “excess of” was replaced by “high-in” in the final implementation of the law. Conclusions A simple black-&-white stop sign warning label was the best option to flag pre-packaged foods with an excess of energy or nutrients of concern for non-communicable diseases; this FoP warning label was implemented in Chile in June 2016 as part of the Chilean Food Labeling and Marketing Law.

Objective: Evaluate if an intervention based on nutritional counseling decreases total sugars and energy consumption in overweight and obese pregnant women, compared to their previous consumption and compared to women who only received routine counseling. Methods: Randomized study of two groups: dietary counseling (Intervention Group: IG) and routine counseling (Control Group: CG). The intervention consisted of three educational sessions focused on decreasing intake of foods that most contribute to sugars consumption. Changes in sugars and energy consumption were evaluated by a food frequency questionnaire before and after the intervention. Results: We evaluated 433 pregnant women, 272 in IG and 161 in CG, who before intervention had a mean consumption of 140 g total sugars and 2134 kcal energy per day. At the end of the intervention, the IG showed 15 g/day lower consumption of total sugars (95% CI: −25 and −5 g/day), 2% less total energy from sugars (95% CI: −3% and −1% g/day), and 125 kcal/day less energy than the CG (95% CI: −239 and −10 kcal/day). Table sugar, sweets, and soft drinks had the greatest reduction in consumption. Conclusions: The intervention focused on counseling on the decrease in consumption of the foods that most contribute to sugars consumption in overweight and obese pregnant women was effective in decreasing total sugars and energy consumption, mainly in the food groups high in sugars. Future studies should examine if this intervention has an effect on maternal and fetal outcomes.