Risk Of Cancer In Premenopausal Women Research Articles

A Narrative Review of Breastfeeding and Its Correlation With Breast Cancer: Current Understanding and Outcomes.

Breastfeeding has been extensively studied in relation to breast cancer risk. The results of the reviewed studies consistently show a decreased risk of breast cancer associated with breastfeeding, especially for 12 months or longer. This protective effect is attributed to hormonal, immunological, and physiological changes during lactation. Breastfeeding also appears to have a greater impact on reducing breast cancer risk in premenopausal women and specific breast cancer subtypes. Encouraging breastfeeding has dual benefits: benefiting infants and reducing breast cancer risk long-term. Healthcare professionals should provide evidence-based guidance on breastfeeding initiation, duration, and exclusivity, while public health policies should support breastfeeding by creating enabling environments. This review examines the existing literature and analyzes the correlation between breastfeeding and breast cancer risk.

Urinary 2- to 16α-hydroxyestrone ratio did not change with cruciferous vegetable intake in premenopausal women.

The mass ratio of urinary 2-hydroxyestrone to 16-α-hydroxyestrone (2:16) is hypothesized as a biomarker of breast cancer risk in premenopausal women, with higher ratios being theoretically protective. Cruciferous vegetable intake has been associated with higher urinary 2:16 in some studies. We investigated whether a whole-food supplement made from dried Brussels sprouts and kale would increase urinary 2:16 in comparison with placebo or cruciferous vegetables in women. This randomized, parallel arm, placebo-controlled, partly blinded study included 78 healthy premenopausal women (38-50 y) with screening urinary 2:16 ≤3.0. Subjects received either six capsules containing 550 mg dried Brussels sprouts and kale per capsule, 40 g daily alternating broccoli or Brussels sprouts, or placebo for eight weeks. Urinary 2:16 and creatinine were measured at baseline, four, and eight weeks. Intent-to-treat repeated measures-ANOVA with multiple imputation (n=100) for missing values identified no treatment effect (P=0.9) or treatment-by-time interaction (P=0.6); however, a significant time effect was noted (P=0.02). Per-protocol analyses including complete cases found no treatment effect (P=1) or treatment-by-time interaction (P=0.6); however, the significant time effect remained (P=0.03). Restricting analysis to subjects with >80% compliance maintained the time effect (P=0.02). Using Pearson correlations, android-pattern and android:gynoid fat were predictive of change (P≤0.05). In conclusion, neither cruciferous supplements nor an added vegetable serving altered urinary 2:16 in premenopausal women with eight weeks treatment. This ratio did vary with time, which is important for designing future trials.

Combined and progestagen-only hormonal contraceptives and breast cancer risk: A UK nested case-control study and meta-analysis.

Current or recent use of combined oral contraceptives (containing oestrogen+progestagen) has been associated with a small increase in breast cancer risk. Progestagen-only contraceptive use is increasing, but information on associated risks is limited. We aimed to assess breast cancer risk associated with current or recent use of different types of hormonal contraceptives in premenopausal women, with particular emphasis on progestagen-only preparations. Hormonal contraceptive prescriptions recorded prospectively in a UK primary care database (Clinical Practice Research Datalink [CPRD]) were compared in a nested case-control study for 9,498 women aged <50 years with incident invasive breast cancer diagnosed in 1996 to 2017, and for 18,171 closely matched controls. On average, 7.3 (standard deviation [SD] 4.6) years of clinical records were available for each case and their matched controls prior to the date of diagnosis. Conditional logistic regression yielded odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer by the hormonal contraceptive type last prescribed, controlled for age, GP practice, body mass index, number of recorded births, time since last birth, and alcohol intake. MEDLINE and Embase were searched for observational studies published between 01 January 1995 and 01 November 2022 that reported on the association between current or recent progestagen-only contraceptive use and breast cancer risk in premenopausal women. Fixed effects meta-analyses combined the CPRD results with previously published results from 12 observational studies for progestagen-only preparations. Overall, 44% (4,195/9,498) of women with breast cancer and 39% (7,092/18,171) of matched controls had a hormonal contraceptive prescription an average of 3.1 (SD 3.7) years before breast cancer diagnosis (or equivalent date for controls). About half the prescriptions were for progestagen-only preparations. Breast cancer ORs were similarly and significantly raised if the last hormonal contraceptive prescription was for oral combined, oral progestagen-only, injected progestagen, or progestagen-releasing intrauterine devices (IUDs): ORs = 1.23 (95% CI [1.14 to 1.32]; p < 0.001), 1.26 (95% CI [1.16 to 1.37]; p < 0.001), 1.25 (95% CI [1.07 to 1.45]; p = 0.004), and 1.32 (95% CI [1.17 to 1.49]; p < 0.001), respectively. Our meta-analyses yielded significantly raised relative risks (RRs) for current or recent use of progestagen-only contraceptives: oral = 1.29 (95% CI [1.21 to 1.37]; heterogeneity χ25 = 6.7; p = 0.2), injected = 1.18 (95% CI [1.07 to 1.30]; heterogeneity χ28 = 22.5; p = 0.004), implanted = 1.28 (95% CI [1.08 to 1.51]; heterogeneity χ23 = 7.3; p = 0.06), and IUDs = 1.21 (95% CI [1.14 to 1.28]; heterogeneity χ24 = 7.9; p = 0.1). When the CPRD results were combined with those from previous published findings (which included women from a wider age range), the resulting 15-year absolute excess risk associated with 5 years use of oral combined or progestagen-only contraceptives in high-income countries was estimated at: 8 per 100,000 users from age 16 to 20 years and 265 per 100,000 users from age 35 to 39 years. The main limitation of the study design was that, due to the nature of the CPRD data and most other prescription databases, information on contraceptive use was recorded during a defined period only, with information before entry into the database generally being unavailable. This means that although our findings provide evidence about the short-term associations between hormonal contraceptives and breast cancer risk, they do not provide information regarding longer-term associations, or the impact of total duration of contraceptive use on breast cancer risk. This study provides important new evidence that current or recent use of progestagen-only contraceptives is associated with a slight increase in breast cancer risk, which does not appear to vary by mode of delivery, and is similar in magnitude to that associated with combined hormonal contraceptives. Given that the underlying risk of breast cancer increases with advancing age, the absolute excess risk associated with use of either type of oral contraceptive is estimated to be smaller in women who use it at younger rather than at older ages. Such risks need be balanced against the benefits of using contraceptives during the childbearing years.

Oral Contraceptive Use and Assessment of Breast Cancer Risk among Premenopausal Women via Molecular Characteristics: Systematic Review with Meta-Analysis.

Breast cancer is divided into four molecular subtypes. Each one has distinct clinical features. The aim of this study was to assess individual breast cancer subtype risk in premenopausal women taking oral contraceptives (OCs). Databases (MEDLINE; PubMed, EMBASE, and the Cochrane Library) were searched to January 2022 to identify case-control studies meeting the inclusion criteria. The influence of OCs intake on the risk of ER-positive breast cancer (ER+BC) was revealed to be non-significant with regard to reduction: OR = 0.9134, 95% CI: 0.8128 to 1.0265, p = 0.128. Assessment of ER-negative subtype breast cancer (ER-BC) risk indicated that OCs use significantly increased the risk: OR = 1.3079, 95% CI: 1.0003 to 1.7100, p = 0.050. Analysis for HER2-positive breast cancer (HER2+BC) risk showed that OCs use statistically non-significantly lowered the risk: OR = 0.8810, 95% CI: 0.5977 to 1.2984, p = 0.522. Meta-analysis with regard to Triplet-negative breast cancer (TNBC) risk showed non-statistically significant increased risk: OR = 1.553, 95% CI: 0.99 to 2.43, p = 0.055. The findings of the meta-analysis suggest that breast cancer risk in premenopausal women may vary with respect to molecular subtypes. Extensive scientific work is still necessary in order to understand the impact of OCs use on breast cancer risk in young women.

Air pollution and green spaces in relation to breast cancer risk among pre and postmenopausal women: A mega cohort from Catalonia

BackgroundThe association between air pollution and green spaces with breast cancer risk stratified by menopausal status has not been frequently investigated despite its importance given the different impact of risk factors on breast cancer risk depending on menopausal status. ObjectivesTo study the association between air pollution, green spaces and pre and postmenopausal breast cancer risk. MethodsWe conducted a population-based cohort study using electronic primary care records in Catalonia. We included women aged 17–85 years free of cancer at study entry between 2009 and 2017. Our exposures were particulate matter <2.5 μm (PM2.5) & <10 μm (PM10), nitrogen dioxide (NO2), normalized difference vegetation index (NDVI), and percentage of green spaces estimated at the census tract level. Breast cancer was identified with ICD-10 code C50. We estimated cause-specific hazard ratios (HR) for the relationship between each individual exposure and pre and postmenopausal breast cancer risk, using linear and non-linear models. ResultsOf the 1,054,180 pre and 744,658 postmenopausal women followed for a median of 10 years, 6,126 and 17,858 developed breast cancer, respectively. Among premenopausal women, only very high levels of PM10 (≥46 μg/m3) were associated with increased cancer risk (compared to lower levels) in non-linear models. Among postmenopausal women, an interquartile range increase in PM2.5 (HR:1.03; 95%CI:1.01–1.04), PM10 (1.03; 1.01–1.05), and NO2 (1.05; 1.02–1.08) were associated with higher cancer risk. NDVI was negatively associated with decreased cancer risk only among postmenopausal women who did not change residence during follow-up (0.84; 0.71–0.99) or who were followed for at least three years (0.82; 0.69–0.98). DiscussionLiving in areas with high concentrations of PM2.5, PM10, and NO2 increases breast cancer risk in postmenopausal women while long-term exposure to green spaces may decrease this risk. Only very high concentrations of PM10 increase breast cancer risk in premenopausal women.

Consecutive gain and loss in body weight and waist circumference with risk of subsequent breast cancer in Korean women.

This study investigated the association between longitudinal changes in weight and waist circumference and breast cancer risk according to menopausal status. This retrospective cohort study used data from the population-based Korean National Health Insurance Service (NHI) database. The study population included women aged ≥40 years who consecutively underwent three biennial breast cancer screenings between 2009-2014 and were followed up until 2020. The percentage changes in weight and waist circumference during the three screenings were calculated and categorized into five groups based on the level of increase or decrease in these two factors. Hazard ratios (HRs) and 95% confidence intervals (95% CI) for breast cancer risk were calculated and adjusted for other factors. Of 691,253 premenopausal and 1,519,211 postmenopausal women, 9485 and 12,553 breast cancer cases were identified, respectively, during a median 6.9 follow-up years. Postmenopausal women with two consecutive weight gains had an increased risk of breast cancer risk (HR = 1.11, 95% CI = 1.01 to 1.22); meanwhile, consecutive weight loss was associated with a decreased risk (HR = 0.84, 95% CI = 0.76 to 0.93). Single time and continuous decreases in waist circumference were associated with a decreased risk (HR = 0.91, 95% CI = 0.85 to 0.98, and HR = 0.84, 95% CI = 0.76-0.93), while single time and continuous increases were associated with an increased risk (HR = 1.08, 95% CI = 1.01 to 1.15, and HR = 1.13, 95% CI = 1.04 to 1.22). Single weight gain was associated with the increased breast cancer risk in premenopausal women (HR = 1.07, 95% CI = 1.01 1.13). Our findings suggest a dose-response relationship between weight, waist circumference change, and the risk of future breast cancer.

Energy homeostasis genes modify the association between serum concentrations of IGF-1 and IGFBP-3 and breast cancer risk

Breast cancer is a multifactorial disease in which the interplay among multiple risk factors remains unclear. Energy homeostasis genes play an important role in carcinogenesis and their interactions with the serum concentrations of IGF-1 and IGFBP-3 on the risk of breast cancer have not yet been investigated. The aim of this study was to assess the modifying effect of the genetic variation in some energy homeostasis genes on the association of serum concentrations of IGF-1 and IGFBP-3 with breast cancer risk. We analyzed 78 SNPs from 10 energy homeostasis genes in premenopausal women from the 4-Corner’s Breast Cancer Study (61 cases and 155 controls) and the Mexico Breast Cancer Study (204 cases and 282 controls). After data harmonization, 71 SNPs in HWE were included for interaction analysis. Two SNPs in two genes (MBOAT rs13272159 and NPY rs16131) showed an effect modification on the association between IGF-1 serum concentration and breast cancer risk (Pinteraction < 0.05, adjusted Pinteraction < 0.20). In addition, five SNPs in three genes (ADIPOQ rs182052, rs822391 and rs7649121, CARTPT rs3846659, and LEPR rs12059300) had an effect modification on the association between IGFBP-3 serum concentration and breast cancer risk (Pinteraction < 0.05, adjusted Pinteraction < 0.20). Our findings showed that variants of energy homeostasis genes modified the association between the IGF-1 or IGFBP-3 serum concentration and breast cancer risk in premenopausal women. These findings contribute to a better understanding of this multifactorial pathology.

Insulin resistance and the development of breast cancer in premenopausal women: the Kangbuk Samsung Health Study.

Research on the role of insulin resistance (IR) in breast cancer risk in premenopausal women is scarce. We aimed to investigate the relationship between IR and the development of breast cancer in premenopausal women. We analyzed the prospective association of IR and incident breast cancer in premenopausal women without breast cancer at baseline using a subsample of the Kangbuk Samsung Health Study. Among 134,488 Korean premenopausal women, 696 women developed incident breast cancers during a median follow-up of 4.34years. After adjustment for dense breast and other potential confounders, HR (95% CI) for incident breast cancer comparing HOMA-IR quintiles 2, 3, 4, and 5 to the first quintile was 0.91 (0.71-1.17), 0.89 (0.69-1.15), 0.75 (0.57-0.98), and 0.87 (0.65-1.16), respectively (P for trend = 0.117), while HR (95% CI) comparing insulin quintiles 2, 3, 4, and 5 to the first quintile was 1.02 (0.80-1.30), 0.90 (0.69-1.16), 0.72 (0.54-0.96), and 0.96 (0.72-1.28), respectively (P for trend = 0.151). This pattern did not significantly differ by obesity. These results were attenuated and no longer significant in time-dependent analyses where updated status of insulin and other covariates over time were treated as time-varying covariates. Our findings do not support the positive relationship of IR with the development of breast cancer in premenopausal women, unlike in postmenopausal women. Thus, the role of IR as a risk factor for breast cancer may differ by menopausal status.

Breast adipose regulation of premenopausal breast epithelial phenotype involves interleukin 10.

Epidemiological studies inversely associate BMI with breast cancer risk in premenopausal women, but the pathophysiological linkage remains ill-defined. Despite the documented relevance of the 'local' environment to breast cancer progression and the well-accepted differences in transcriptome and metabolic properties of anatomically distinct fat depots, specific breast adipose contributions to the proliferative potential of non-diseased breast glandular compartment are not fully understood. To address early breast cancer causation in the context of obesity status, we compared the cellular and molecular phenotypes of breast adipose and matched breast glandular tissue from premenopausal non-obese (mean BMI = 27 kg/m2) and obese (mean BMI = 44 kg/m2) women. Breast adipose from obese women showed higher expression levels of adipogenic, pro-inflammatory, and estrogen synthetic genes than from non-obese women. Obese breast glandular tissue displayed lower proliferation and inflammatory status and higher expression of anti-proliferative/pro-senescence biomarkers TP53 and p21 than from non-obese women. Transcript levels for T-cell receptor and co-receptors CD3 and CD4 were higher in breast adipose of obese cohorts, coincident with elevated adipose interleukin 10 (IL10) and FOXP3 gene expression. In human breast epithelial cell lines MCF10A and HMEC, recombinant human IL10 reduced cell viability and CCND1 transcript levels, increased those of TP53 and p21, and promoted (MCF10A) apoptosis. Our findings suggest that breast adipose-associated IL10 may mediate paracrine interactions between non-diseased breast adipose and breast glandular compartments and highlight how breast adipose may program the local inflammatory milieu, partly by recruiting FOXP3+ T regulatory cells, to influence premenopausal breast cancer risk.

Association between serum lipids and breast cancer risk in premenopausal women: systematic review and meta-analysis.

ObjectiveAssociations between serum lipids and their individual components with premenopausal breast cancer risk are unclear. This meta-analysis summarized the literature on serum lipids and premenopausal breast cancer risk to elucidate their relationship.MethodsEligible studies were identified by searching the PubMed, Embase, China National Knowledge Infrastructure, and Wanfang databases until 31 December 2020. Standardized mean difference (SMD) scores with 95% confidence intervals (95%CIs) were used to assess the impact of serum lipids on premenopausal breast cancer risk. The I2 statistic was calculated to measure the percentage of heterogeneity, and Egger’s test was performed to measure publication bias.ResultsThirteen studies were included. The SMD scores of triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) were 12.90 (95%CI: 7.19–18.61) and 31.43 (95%CI: 8.72–54.15), respectively. The SMD scores of total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) were not significantly different between the groups. The included studies were highly heterogeneous. There were no publication biases found in TC, LDL-C, or HDL-C analyses, whereas publication bias was present in the TG analysis.ConclusionsTG and LDL-C were higher in premenopausal breast cancer patients than in women without breast cancer. However, no significant differences were found in TC or HDL-C levels.

Abstract 2574: Collagen density and obesity promote mammary gland inflammation

Abstract Recent epidemiological studies suggest that the risk factors of breast density and obesity together increase breast cancer risk in premenopausal women, and these women have a worsened prognosis following breast cancer diagnosis. Although the underlying causes of increased risk associated with dense breasts and obesity have individually been explored, little is known about how these underlying risk factors interact together to enhance breast cancer risk. To model breast density, we used heterozygous Col1a1tmjae mice, that have a mutation that limits collagen degradation, leading to increased mammary collagen deposition. Heterozygous (het) mice or wild type (wt) litter mates were fed either a control diet (CD) or a high fat diet (HFD) to induce obesity. We quantified F4/80-positive macrophages within mammary glands using immunohistochemistry. We observed significantly increased numbers of macrophages in mammary glands of CD/het, HFD/wt and HFD/het mice compared to CD/wt mice. We observed significantly enhanced picrosirius red stained collagen surrounding mammary ducts from CD/het, HFD/wt, and HFD/het mice compared to those from CD/wt mice. Notably, HFD/het mice had significantly more collagen surrounding ducts than in mammary glands from CD/het mice. These results may suggest that obesity enhances collagen deposition and macrophage-driven inflammation within dense breast tissue in the mammary glands of non-tumor-bearing mice. Citation Format: Abbey E. Williams, Abbey E. Williams, Erica Hoffman, Julia Warren, Suzanne Ponik, Lisa M. Arendt. Collagen density and obesity promote mammary gland inflammation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2574.

Association of folate intake and plasma folate level with the risk of breast cancer: a dose-response meta-analysis of observational studies.

Epidemiological studies showing the correlation between folate and the breast cancer risk have revealed inconsistent results. Hence, we conducted a dose-response meta-analysis of observational studies to obtain more reliable conclusions. We searched PubMed and Embase for studies published before April 2019 and identified 39 studies on folate intake and 12 studies on plasma folate level. The combined odds ratios (ORs) and 95% confidence intervals (CIs) were extracted to estimate the breast cancer risk. Folate intake was inversely correlated with the breast cancer risk when the highest and lowest categories (OR = 0.85, 95% CI = 0.79–0.92) were compared, and the dose-response result showed that folate intake had a linear correlation with the breast cancer risk. Moreover, a higher folate intake correlated with a lower breast cancer risk in premenopausal women (OR = 0.80, 95% CI = 0.66–0.97), but not in postmenopausal women (OR = 0.94, 95% CI = 0.83–1.06). However, plasma folate levels were not correlated with the breast cancer risk (OR = 0.98, 95% CI = 0.82–1.17). Folate intake was negatively correlated with the breast cancer risk; however, its practical clinical significance requires further study. Furthermore, additional folate supplements should be considered carefully.

Metformin and Chemoprevention: Potential for Heart-Healthy Targeting of Biologically Aggressive Breast Cancer.

Currently, tamoxifen is the only drug approved for reduction of breast cancer risk in premenopausal women. The significant cardiovascular side effects of tamoxifen, coupled with lack of a survival benefit, potential for genotoxicity, and failure to provide a significant risk-reduction for estrogen receptor-negative breast cancer, all contribute to the low acceptance of tamoxifen chemoprevention in premenopausal women at high-risk for breast cancer. While other prevention options exist for postmenopausal women, there is a search for well-tolerated prevention agents that can simultaneously reduce risk of breast cancers, cardiovascular disease, and type-2 diabetes. Metformin is a well-tolerated oral biguanide hypoglycemic agent that is prescribed worldwide to over 120 million individuals with type-2 diabetes. Metformin is inexpensive, safe during pregnancy, and the combination of metformin, healthy lifestyle, and exercise has been shown to be effective in preventing diabetes. There is a growing awareness that prevention drugs and interventions should make the “whole woman healthy.” To this end, current efforts have focused on finding low toxicity alternatives, particularly repurposed drugs for chemoprevention of breast cancer, including metformin. Metformin's mechanisms of actions are complex but clearly involve secondary lowering of circulating insulin. Signaling pathways activated by insulin also drive biologically aggressive breast cancer and predict poor survival in women with breast cancer. The mechanistic rationale for metformin chemoprevention is well-supported by the scientific literature. Metformin is cheap, safe during pregnancy, and has the potential to provide heart-healthy breast cancer prevention. On-going primary and secondary prevention trials will provide evidence whether metformin is effective in preventing breast cancer.

Anthropometry, bone mineral density and risk of breast cancer in premenopausal and postmenopausal Saudi women.

Anthropometry and bone mineral density are linked to hormonal imbalance, which plays a possible role in breast carcinogenesis. The current study was designed to explore the relationship between selected anthropometric and bone mineral density parameters and the risk of breast cancer in premenopausal and postmenopausal Saudi women. A cross-sectional study was carried out among premenopausal (n = 308) and postmenopausal (n = 148) women at two Medical Cities in Riyadh, Saudi Arabia from May 2015 to June 2016. Selected anthropometric measurements were obtained from 456 women; 213 of them had breast cancer. Bone mineral density was also measured using dual-energy X-ray absorptiometry. Greater waist circumference was significantly correlated with a higher breast cancer risk in premenopausal women (OR = 1.02, p = 0.03) but not in postmenopausal women. Greater triceps skinfold thickness had been found to be significantly correlated with a higher risk of breast cancer in premenopausal (OR = 1.06, p = 0.001) and postmenopausal (OR = 1.06, p = 0.001) women. However, bone mineral density was not significantly associated with breast cancer risk in either group of participants. Breast cancer risk was significantly associated with waist circumference and triceps skinfold thickness in premenopausal women and with only triceps skinfold thickness in postmenopausal women.

Erratum: Addendum: Metabolic Syndrome, and Particularly the Hypertriglyceridemic-Waist Phenotype, Increases Breast Cancer Risk, and Adiponectin Is a Potential Mechanism: A Case-Control Study in Chinese Women.

[This corrects the article DOI: 10.3389/fendo.2019.00905.].

Metabolic Syndrome, and Particularly the Hypertriglyceridemic-Waist Phenotype, Increases Breast Cancer Risk, and Adiponectin Is a Potential Mechanism: A Case-Control Study in Chinese Women.

Objective: To investigate the association between metabolic syndrome and breast cancer and to elucidate the potential mechanism underlying this association.Patients and Methods: Based on baseline data drawn from 21 hospitals in 11 provinces of China, we performed a case–control study among 1,127 women (595 cases and 532 controls), divided into premenopausal, and postmenopausal subgroups. Student's t test, Pearson's χ2 test, and logistic regression analyses were performed to ascertain the association between breast cancer and metabolic syndrome, including all of its components. In addition, we attempted to clarify the potential role of adiponectin in this association.Results: Among the components of metabolic syndrome, abnormal waist circumference was the component that markedly increased breast cancer risk in premenopausal women (OR 1.447, 95% CI 1.043–2.006). Metabolic syndrome with clusters of special risk factors showed an association with breast cancer risk. Among all these components of metabolic syndrome, the hypertriglyceridemic-waist (HW) phenotype significantly increased breast cancer risk (OR 1.56, 95% CI 1.02–2.39), regardless of menopausal status, rendering it a strong predictor of breast cancer. Total adiponectin levels and high-molecular-weight adiponectin were reversely associated with metabolic syndrome. In addition, total adiponectin levels among breast cancer patients were much lower than among controls (p = 0.005) only in the HW phenotype subgroup. Furthermore, the HW phenotype was associated with increased risk of estrogen receptor/progesterone receptor-positive (ER+/PR+) breast cancer, with a 95% (OR = 1.95, 95% CI:1.21–3.13) increase. However, there was no significant association between the HW phenotype and both ER+/PR– and ER–/PR– subtypes. These results suggested that low adiponectin levels may be a mechanism that explains the association between the HW phenotype and breast cancer risk.Conclusion: Metabolic syndrome with special cluster factors is related to breast cancer risk; in particular, the HW phenotype can be regarded as a strong predictor of breast cancer. As an important factor involved in fat metabolism, adiponectin may strongly predict metabolic syndrome, especially the HW phenotype and breast cancer. Further research into this mechanism and epidemiological studies are needed. This study provides new evidence for the role of a healthy lifestyle in preventing breast cancer.

Association between matrix metalloproteinase-9 gene polymorphism and breast cancer in Brazilian women

OBJECTIVE:This study aimed to determine the relationship between rs17576 (MMP-9) polymorphism and increased cancer risk in a Brazilian breast cancer cohort.METHODS:This study included 141 women (71 breast cancer patients and 70 controls without breast cancer) who donated 3 mL of their peripheral blood for genomic DNA extraction. This DNA was then genotyped using a real-time polymerase chain reaction.RESULTS:The AG (rs17576) genotype was identified in 26 (18.43%) participants in the case group and in 22 (15.60%) participants in the control group (p=0.274), while the GG genotype was identified in ten (7.09%) participants in the case group and in one (0.70%) participant in the control group (p<0.003 - OR (95% CI) 13.13 (1.73, 593.08). No significant difference in the incidence rates was observed for AG or GG rs17576 genotypes in premenopausal women, p=0.813 and p=0.556, respectively. However, in postmenopausal women, the AG genotype was shown to occur in 14 (22.5%) participants in the case group and in 4 (6.45%) participants in the control (p<0.043), while GG genotype occurred in eight (12.90%) of the individuals in the case group and in none of the individuals in the control group (p<0.006).CONCLUSION:In this study, the MMP-9 rs17576 GG polymorphic variant was shown to be significantly associated with breast cancer risk in premenopausal women, while the AG and GG genotypes were associated with increased cancer risk in postmenopausal women.

Risk factors for endometrial cancer: An umbrella review of the literature.

Although many risk factors could have causal association with endometrial cancer, they are also prone to residual confounding or other biases which could lead to over- or underestimation. This umbrella review evaluates the strength and validity of evidence pertaining risk factors for endometrial cancer. Systematic reviews or meta-analyses of observational studies evaluating the association between non-genetic risk factors and risk of developing or dying from endometrial cancer were identified from inception to April 2018 using PubMed, the Cochrane database and manual reference screening. Evidence was graded strong, highly suggestive, suggestive or weak based on statistical significance of random-effects summary estimate, largest study included, number of cases, between-study heterogeneity, 95% prediction intervals, small study effects, excess significance bias and sensitivity analysis with credibility ceilings. We identified 171 meta-analyses investigating associations between 53 risk factors and endometrial cancer incidence and mortality. Risk factors were categorised: anthropometric indices, dietary intake, physical activity, medical conditions, hormonal therapy use, biochemical markers, gynaecological history and smoking. Of 127 meta-analyses including cohort studies, three associations were graded with strong evidence. Body mass index and waist-to-hip ratio were associated with increased cancer risk in premenopausal women (RR per 5 kg/m2 1.49; CI 1.39-1.61) and for total endometrial cancer (RR per 0.1unit 1.21; CI 1.13-1.29), respectively. Parity reduced risk of disease (RR 0.66, CI 0.60-0.74). Of many proposed risk factors, only three had strong association without hints of bias. Identification of genuine risk factors associated with endometrial cancer may assist in developing targeted prevention strategies for women at high risk.

Association of Overweight and Obesity with Breast Cancer During Premenopausal Period in Asia: A Meta-Analysis.

Background:The association of overweight and obesity with breast cancer risk in premenopausal women and in different ethnicities remains in debate, especially among Asian women. The aim of this systematic review and meta-analysis was to determine the association of overweight and obesity with breast cancer during premenopausal period in Asian women.Methods:We performed a meta-analysis of research articles on the association of overweight and obesity with breast cancer during premenopausal period in Asian women published from January 2000 to July 2018 in article databases of EBSCO, PubMed, and ProQuest. Pooled odds ratios (ORs) were calculated by fixed and random-effect models. Publication bias was visually evaluated using funnel plots, and then statistically assessed using Egger's and Begg's tests. Review Manager 5.3 (RevMan 5.3) and Stata version 14.2 (Stata Corporation) were used to process the data. We reviewed 886 articles.Results:We found 15 studies conducted systematic review continued by meta-analysis of relevant data with 22,362 patients. There was significant association of obesity [OR = 1.36 (95% confidence interval (CI) 1.26–1.47, P < 0.00001)] and overweight [OR = 1.17 (95% CI 1.10–1.25, P < 0.00001)] with breast cancer during premenopausal period in Asian women. In this study, there was no significant publication bias for studies included in overweight and obesity with breast cancer during premenopausal in Asian women.Conclusions:This study suggested association of overweight and obesity with breast cancer during premenopausal period in Asian women.

Association of Body Mass Index and Age With Subsequent Breast Cancer Risk in Premenopausal Women

The association between increasing body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) and risk of breast cancer is unique in cancer epidemiology in that a crossover effect exists, with risk reduction before and risk increase after menopause. The inverse association with premenopausal breast cancer risk is poorly characterized but might be important in the understanding of breast cancer causation. To investigate the association of BMI with premenopausal breast cancer risk, in particular by age at BMI, attained age, risk factors for breast cancer, and tumor characteristics. This multicenter analysis used pooled individual-level data from 758 592 premenopausal women from 19 prospective cohorts to estimate hazard ratios (HRs) of premenopausal breast cancer in association with BMI from ages 18 through 54 years using Cox proportional hazards regression analysis. Median follow-up was 9.3 years (interquartile range, 4.9-13.5 years) per participant, with 13 082 incident cases of breast cancer. Participants were recruited from January 1, 1963, through December 31, 2013, and data were analyzed from September 1, 2013, through December 31, 2017. Body mass index at ages 18 to 24, 25 to 34, 35 to 44, and 45 to 54 years. Invasive or in situ premenopausal breast cancer. Among the 758 592 premenopausal women (median age, 40.6 years; interquartile range, 35.2-45.5 years) included in the analysis, inverse linear associations of BMI with breast cancer risk were found that were stronger for BMI at ages 18 to 24 years (HR per 5 kg/m2 [5.0-U] difference, 0.77; 95% CI, 0.73-0.80) than for BMI at ages 45 to 54 years (HR per 5.0-U difference, 0.88; 95% CI, 0.86-0.91). The inverse associations were observed even among nonoverweight women. There was a 4.2-fold risk gradient between the highest and lowest BMI categories (BMI≥35.0 vs <17.0) at ages 18 to 24 years (HR, 0.24; 95% CI, 0.14-0.40). Hazard ratios did not appreciably vary by attained age or between strata of other breast cancer risk factors. Associations were stronger for estrogen receptor-positive and/or progesterone receptor-positive than for hormone receptor-negative breast cancer for BMI at every age group (eg, for BMI at age 18 to 24 years: HR per 5.0-U difference for estrogen receptor-positive and progesterone receptor-positive tumors, 0.76 [95% CI, 0.70-0.81] vs hormone receptor-negative tumors, 0.85 [95% CI: 0.76-0.95]); BMI at ages 25 to 54 years was not consistently associated with triple-negative or hormone receptor-negative breast cancer overall. The results of this study suggest that increased adiposity is associated with a reduced risk of premenopausal breast cancer at a greater magnitude than previously shown and across the entire distribution of BMI. The strongest associations of risk were observed for BMI in early adulthood. Understanding the biological mechanisms underlying these associations could have important preventive potential.