Decreased Risk Of Breast Cancer Research Articles

The Role of Adiponectin in Breast Cancer: A Meta-Analysis

Published results suggests that high adiponectin level may decrease the risk of breast cancer. However, available evidence on breast cancer is conflicting. Therefore a meta-analysis was performed to assess the association between blood adiponectin and breast cancer risk. PubMed database, Web of Science, Elsevier Science, Springer Link and bibliographies of retrieved articles were searched for epidemiological studies published up to March 2013. Meta-analysis was performed on the combined effect values (OR) as well as standardized mean difference (SMD) including 17 studies. Fixed or random effect pooled measure was selected on the basis of homogeneity test among studies. The publication bias was assessed by the Egger’s regression asymmetry test and Begg’s rank correlation test with Begg’s funnel plot. Subgroup analyses and sensitivity analysis were also performed. A total of 13 studies involving 3578 breast cancer cases and 4363 controls contributed to the OR analysis. The high adiponectin level did not significantly affect breast cancer risk (OR=0.902, 95% CI=0.773–1.053). After excluding articles that were the key contributors to between-study heterogeneity, the OR of high adiponectin level was associated with decreased breast cancer risk (OR=0.838, 95% CI=0.744–0.943). There was a significantly association between high adiponectin level and postmenopausal breast cancer women (OR=0.752, 95%CI=0.604-0.936); and it was not associated with premenopausal breast cancer women (OR=0.895, 95%CI=0.638-1.256). The result of pooled measure on SMD was that the high adiponectin level was associated with decreased breast cancer risk (SMD= -0.348, 95% CI= -0.533--0.614) after excluding articles which were the key contributors to between-study heterogeneity. Our findings indicate that high adiponectin level might decrease the risk of postmenopausal breast cancer. More randomized clinical trials and observational studies are needed to confirm this association with underlying biological mechanisms in the future.

Breast Cancer in Systemic Lupus Erythematosus

Objective: Evidence points to a decreased breast cancer risk in systemic lupus erythematosus (SLE). We analyzed data from a large multisite SLE cohort, linked to cancer registries. Methods: Information on age, SLE duration, cancer date, and histology was available. We analyzed information on histological type and performed multivariate logistic regression analyses of histological types according to age, SLE duration, and calendar year. Results: We studied 180 breast cancers in the SLE cohort. Of the 155 cases with histology information, 11 were referred to simply as ‘carcinoma not otherwise specified'. In the remaining 144 breast cancers, the most common histological type was ductal carcinoma (n = 95; 66%) followed by lobular adenocarcinoma (n = 11; 8%), 15 cancers were of mixed histology, and the remaining ones were special types. In our regression analyses, the independent risk factors for lobular versus ductal carcinoma was age [odds ratio (OR) 1.07, 95% confidence interval (CI) 1.01-1.14] and for the ‘special' subtypes it was age (OR 1.06, 95% CI 1.01-1.10) and SLE duration (OR 1.05, 95% CI 1.00-1.11). Conclusions: Generally, up to 80% of breast cancers are ductal carcinomas. Though our results are not definitive, in the breast cancers that occur in SLE, there may be a slight decrease in the ductal histological type. In our analyses, age and SLE duration were independent predictors of histological status.

Functional MDM4 rs4245739 genetic variant, alone and in combination with P53 Arg72Pro polymorphism, contributes to breast cancer susceptibility

The oncoprotein MDM4 plays an essential role in P53 tumor suppressor pathway through negative regulation of P53 function. It has been reported that the rs4245739 A>C polymorphism located in the MDM4 3'-untranslated region creates a miR-191 target site and results in decreased MDM4 expression. Therefore, we investigated the association of the MDM4 rs4245739 polymorphism as well as the P53 Arg72Pro genetic variant with the breast cancer risk. Genotypes were determined in two independent case-control sets consisting of 1100 breast cancer cases and 1400 controls from two regions of China. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. Our results demonstrated that the MDM4 rs4245739 AC and CC genotypes were significantly associated with decreased breast cancer risk compared to the AA genotype in both the case-control sets (Jinan set: OR=0.55, 95% CI 0.40-0.76, P=2.3×10(-4); Huaian set: OR=0.41, 95% CI 0.25-0.67, P=3.1×10(-4)). The P53 Arg/Pro genotype or Pro/Pro genotype was significantly associated with an increased risk of developing breast cancer, compared to the P53 Arg/Arg genotype in both the case-control sets (all P<0.05). Interestingly, we observed a combinational effect between MDM4 rs4245739 and P53 Arg72Pro variants in attenuating breast cancer risk, highlighting the importance of the P53 tumor suppressor pathway genes during malignant transformation. Our results also support the hypothesis that genetic variants interrupting miRNA-mediated gene regulation might be important genetic modifiers of breast cancer risk.

Plasma enterolactone and breast cancer risk in the Nurses’ Health Study II

Lignans are plant-based phytoestrogens with both estrogenic and anti-estrogenic properties that may be important for breast carcinogenesis. Retrospective studies have observed decreased breast cancer risk associated with highcirculating enterolactone concentrations, a biomarker of lignan intake, but results from prospective studies are conflicting. To prospectively examine this association, we measured plasma enterolactone levels in 802 breast cancer cases and 802 matched controls nested among predominantly premenopausal women in the Nurses' Health Study II cohort. We used conditional logistic regression and polytomous logistic regression models, adjusting for known breast cancer risk factors, to calculate relative risks (RR) and 95% confidence intervals (CI). Compared to women with enterolactone concentrations ≤4nmol/L, the multivariate-adjusted RRs for breast cancer were 1.18 (95% CI 0.86-1.62), 0.91 (95% CI 0.66-1.25), and 0.96 (95% CI 0.70-1.33) for women with enterolactone levels in the second to the fourth quartiles, respectively; P trend=0.60. Results were similar across tumors defined by estrogen and progesterone receptor status. Among premenopausal women with follicular estradiol levels below the median (<47pg/mL), women in the highest category of enterolactone levels had a 51% lower breast cancer risk compared to those in the lowest category (95% CI 0.27-0.91); P trend=0.02. No association was observed among women with high-follicular estradiol levels (≥47pg/mL), (comparable RR=1.39, 95% CI 0.73-2.65; P interaction=0.02). We did not observe an overall association between plasma enterolactone and breast cancer risk in a large nested case-control study of US women. However, a significant inverse association was observed among premenopausal women with low-follicular estradiol levels, suggesting that enterolactone may be important in a low-estrogen environment. This should be confirmed in future studies.

Highlights of This Issue

The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) guidelines encourage cancer survivors to follow their cancer prevention recommendations. Inoue-Choi and colleagues assessed whether adherence to the WCRF/AICR guidelines was associated with lower mortality among older female cancer survivors. The authors report that women with the highest adherence levels had lower all-cause mortality, compared with women with the lowest adherence level. Adherence to the physical activity recommendation had the strongest association with lower all-cause and disease-specific mortality. This report emphasizes the importance of leading a healthy lifestyle after a cancer diagnosis.Heterogeneous diseases are comprised of multiple subtypes, each with its own unique set of biomarkers, affecting the design and analysis of biomarker discovery studies. Wellstrom and colleagues used Monte Carlo simulation to compare 8 biomarker selection methods for homogeneous and heterogeneous diseases with single-and 2-stage designs. The authors report that more than 2-fold larger sample sizes were needed for heterogeneous diseases, compared with homogeneous diseases. The report includes important sample size requirements and study design guidance for biomarker discovery studies.Exercise can decrease breast cancer risk, and this could be mediated through changes in estrogen metabolism in premenopausal women. Smith and colleagues investigated the effects of exercise on premenopausal estrogen metabolism. Women were randomly assigned into an aerobic exercise intervention group or a sedentary control group, and urinary levels of estrogens and estrogen metabolites were measured at baseline and at the end of the study. The exercise intervention resulted in a significant increase in a particular estrogen metabolite ratio (2-OHE1/16α-OHE1), suggesting that changes in premenopausal estrogen metabolism may be a mechanism by which increased physical activity lowers breast cancer risk.Hepatitis B–linked liver cancer disproportionately affects Hmong Americans; this population experiences liver cancer at a rate 6- to 7-fold greater than that of non-Hispanic whites. Chen and colleagues present a 5-year randomized controlled trial testing a lay health worker (LHW) intervention to promote hepatitis B virus (HBV) testing among Hmong adults. Intervention group participants were more likely to report receiving HBV serologic testing and showed increased knowledge scores, compared with the control group. Although the LHW intervention significantly increased Hmong HBV screening rates, the most often cited reason for testing was a doctor's recommendation.

A Linked-Registry Study of Gestational Factors and Subsequent Breast Cancer Risk in the Mother

Women who were younger at their first live birth have a reduced breast cancer risk. Other pregnancy characteristics, including complications, also may affect risk but because they are rare, require large datasets to study. The association of pregnancy history and breast cancer risk was assessed in a population-based study including 22,646 cases diagnosed in Washington State 1974 to 2009, and 224,721 controls, frequency matched on parity, age, calendar year of delivery, and race/ethnicity. Information on prediagnosis pregnancies derived from linked birth certificate and hospital discharge databases. Adjusted odd ratios (ORs) and 95% confidence intervals (CI) were calculated. Multiple gestation pregnancies were associated with decreased breast cancer risk (OR, 0.65; 95% CI, 0.57-0.74) as was prepregnancy obesity (OR, 0.76; 95% CI, 0.65-0.90). Infant birth weight was positively associated (6% per 1,000 g; 95% CI, 3%-9%). The ORs for first trimester bleeding (OR, 3.35; 95% CI, 1.48-7.55) and placental abnormality/insufficiency (OR, 2.24; 95% CI, 1.08-4.67) were increased in women diagnosed at age 50+ years and 15+ years after the index pregnancy. Results were similar in analyses restricted to first pregnancies, those closest to diagnosis, and when excluding in situ disease. These data suggest that multiple gestation pregnancies are protective, whereas delivering larger infants increases risk for later development of maternal breast cancer. Placental abnormalities that result in bleeding in pregnancy also may reverse the long-term protection in postmenopausal women associated with parity. Certain pregnancy characteristics seem to be associated with later maternal breast cancer risk.

The Effects of Aerobic Exercise on Estrogen Metabolism in Healthy Premenopausal Women

It is well accepted that exercise can decrease breast cancer risk. Limited clinical evidence suggests that this risk could be mediated through changes in estrogen metabolism in premenopausal women. Our objective was to investigate the effects of exercise on premenopausal estrogen metabolism pertinent to breast cancer risk. Sedentary, healthy, young eumenorrheic women were randomized into an intervention of 30 minutes of moderate-to-vigorous aerobic exercise five times a week for approximately 16 weeks (n = 212), or into a usual-lifestyle sedentary control group (n = 179). Urinary levels of estrogens [estrone [E1], estradiol, and estriol] and nine estrogen metabolites were measured at baseline and at study end by liquid chromatography/tandem mass spectrometry. The ratios of 2-hydroxyestrone to 16α-hydroxyestrone (2-OHE1/16α-OHE1) and 2-OHE1 to 4-hydroxyestrone (2- OHE1/4-OHE1) were also calculated. The exercise intervention resulted in significant increases in aerobic fitness and lean body mass and a significant decrease in percent body fat. For exercisers who completed the study (n = 165), 2-OHE1/16α-OHE1 increased significantly (P = 0.043), whereas E1 decreased significantly (P = 0.030) in control participants (n = 153). The change from baseline in 2-OHE1/16α-OHE1 was significantly different between groups (P = 0.045), even after adjustment for baseline values. The exercise intervention resulted in a significant increase in the 2-OHE1/16α-OHE1 ratio but no differences in other estrogen metabolites or ratios. Our results suggest that changes in premenopausal estrogen metabolism may be a mechanism by which increased physical activity lowers breast cancer risk.

Mammographic Density and Risk of Breast Cancer

The radiographic appearance of the breast on mammography varies among women, and reflects variations in breast tissue composition and the different X-ray attenuation characteristics of these tissues. Fat is radiologically lucent and appears dark on a mammogram. Connective and epithelial tissues are radiologically dense and appear light. These variations in appearance are commonly described as the percentage of the breast image that is radiologically dense, or as percent mammographic density (PMD). There is now extensive evidence that PMD is a risk factor for breast cancer, with a 4- to 6-fold gradient in risk between women with 75% or more PMD compared with those with 10% or less. However, the accuracy of risk prediction in individual women is modest. The extent of PMD is associated inversely with greater age, parity, and weight, and is reduced by the menopause and by tamoxifen. PMD is positively associated with greater height, a family history of breast cancer, and is increased by combined hormone therapy. The relative risk associated with density is substantially larger than the relative risk of breast cancer associated with a family history of the disease or any of the menstrual and reproductive risk factors. It is estimated that the risks of breast cancer attributable to density of 50% or more may be 16% for all breast cancers. Although combined hormone therapy and tamoxifen respectively increase a decrease both PMD and breast cancer risk, there is as yet insufficient evidence to use PMD as a surrogate marker for breast cancer.

Abstract LB-13: Early life exposures and breast cancer (BC) risk among African American (AA) and European American (EA) women.

Abstract Background. There is evidence to suggest that early life exposures including birthweight, history of having been breastfed during infancy, in utero exposure to maternal smoking, and parental education are associated with BC risk. Potential underlying mechanisms include variability in exposure to maternal endogenous sex and growth hormones. Also, parental socioeconomic status may be a proxy for environmental characteristics that impact biological processes in early life, and ultimately influence BC risk. Research has focused on EA women; relatively little is known about associations between early life exposures and BC risk for AA women. Methods. We conducted a case-control study in AA and EA women aged 22-75 years living in metropolitan New York City and eastern New Jersey (Women's Circle of Health Study). Breast cancer cases (AA n=827; EA n=772) were diagnosed with primary, incident, histologically confirmed invasive BC or ductal carcinoma in situ. Controls (AA n=905; EA n=715) were frequency matched to cases on age and race. Birthweight, history of having been breastfed during infancy, history of in utero exposure to maternal smoking, and parental education were by self-report using an interviewer-administered questionnaire. Results. Birthweight was not significantly associated with BC risk in this study for AA or EA women. Having been breastfed during infancy was associated with significantly increased BC risk for both groups (ORAA=1.60, 95% Cl: 1.27-2.02; OREA=1.45, 95% Cl: 1.14-1.85). For EA women, but not AA women, reporting in utero exposure to maternal smoking was associated with significantly decreased BC risk (OR=0.61, 95% Cl: 0.45-0.82). Among AA women, those born to mothers with at least a college degree had a significantly lower BC risk compared to AA women born to mothers with a high school or less education (OR=0.67, 95% Cl: 0.49-0.93). Among EA women, we found no association with maternal education. However, EA women born to fathers with at least a college degree had a significantly lower BC risk compared to EA women born to fathers with a high school or less education (OR=0.65, 95% Cl: 0.51-0.84). Conclusions. Our findings support the hypothesis that early life exposures impact adult BC risk. History of having been breastfed during infancy, in utero exposure to maternal smoking, and parental education were all associated with BC risk. While minor differences in risk estimates were found between EA and AA women, associations were similar. Citation Format: Mark L. Glasgow, Jo Freudenheim, Gary Zirpoli, Elisa Bandera, Christine Ambrosone. Early life exposures and breast cancer (BC) risk among African American (AA) and European American (EA) women. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-13. doi:10.1158/1538-7445.AM2013-LB-13

Abstract 192: Exposure to high saturated fat acid diet in early life changes the susceptibility to breast cancer in adulthood.

Abstract Nutrition is thought to be involved in 30 to 50% of all breast cancer and intake of animal fat seems to be related to the increase of this type of cancer. It has been suggested that breast cancer can originate in early life, including the in utero and lactation periods. Maternal nutrition can modify the fetal environment and induce epigenetics modifications that change the susceptibility of offspring to breast cancer in adulthood. We hypothesized that exposure to high saturated fatty acid diet (HFS) in early life can change gene expression through the remodeling of epigenetic marks and consequently modify the risk of breast cancer. Sprague-Dawley rats were used in our study, which was composed of three groups: CO (female rats exposed to control diet [AIN-93G] in utero and lactation); PG (female rats exposed to HSF in utero) and PL (female rats exposed to HSF in utero and lactation). The distribution of fatty acid in the HSF was 37%, 38% and 24% of saturated, monounsaturated and polyunsaturated, respectively while in the CO diet, the distribution of those fatty acid was 17%, 27% and 55%, respectively. Female rats were euthanized on post-natal day (PND) 50 and blood and mammary tissue collected. Serum samples were assayed for estradiol, progesterone and leptin levels (radioimmunoassay and immunofluorescence). Mammary glands were evaluated for the number of terminal End Buds (TEBs), global DNA methylation (HPLC-DAD) and global histone modification patterns (western blot). Mammary tumor development induced by oral administration of dimethylbenz[a]anthracene (DMBA) on PND50 was also evaluated. Global DNA methylation were also determined in mammary tumors. There were no differences (P&amp;gt;0.05) in maternal caloric intake, offspring birth weight, serum estradiol levels or number of TEBs among the groups. Serum progesterone levels showed a tendency to increase (P=0.07) in the PG group compared to CO group. Compared to others groups, the PL group showed higher (P≤0.05) serum leptin levels. The PG group showed higher levels (P≤0.05) of global trimethylation of histone 3 lysine 9 (H3K9me3) compared to CO group, but no differences were observed (P&amp;gt;0.05) for global DNA methylation and global H3K9/H4K16 acetylation and H3K27/H3K4 trimethylation. The PG group showed lower incidence (P≤0.05) and average number of tumors compared to CO group and higher latency (P≤0.05) compared to PL group. The tumors from PG group presented lower (P≤0.05) global DNA methylation compared to others groups. In conclusion, exposure to HSF in early life influenced the susceptibility of breast cancer in adulthood. But, differently from what we expected the exposure to this diet in utero decreased breast cancer risk. If this exposure is continued through the period of lactation the protective effect is lost. This modification of breast cancer risk in early life seems to involve epigenetics mechanisms like post-translational histone modification. Citation Format: Fábia O. Andrade, Camile C. Fontelles, Mariana Rosim, Tiago F. Oliveira, Ana PM Loureiro, Marcelo M. Rogero, Fernando S. Moreno, Sonia M. De Assis, Leena Hilakivi-Clarke, Luis F. Barbisan, Thomas P. Ong. Exposure to high saturated fat acid diet in early life changes the susceptibility to breast cancer in adulthood. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 192. doi:10.1158/1538-7445.AM2013-192

Need for clarification of data in a recent meta-analysis about polymorphisms in the leptin receptor gene and risk of breast cancer

when all studies were pooled in the meta-analysis (allele contrast model: OR 0.71, 95 % CI 0.551–0.997). In the stratified analysis by ethnicity, significantly increased risks were also found among Asians for allele contrast model (OR 0.414, 95 % CI 0.312–0.550) and dominant model (OR 0.537, 95 % CI 0.370–0.781); for Africans, significantly increased risks were also found for allele contrast model (OR 0.716, 95 % CI 0.595–0.861), homozygote codominant model (OR 0.537,95 % CI 0.370–0.781) and dominant model (OR 1.595, 95 % CI 1.207–2.108). Also, significantly elevated breast cancer risk was associated with LEPR rs1137100 polymorphism for allele contrast (OR 0.666, 95 % CI 0.603–0.720) and homozygote codominant models (OR 0.344, 95 % CI 0.282–0.421). Actually, except the dominant model of LEPR rs1137101 which significantly associated with increased risk of breast cancer (OR 1.595, 95 % CI 1.207–2.108) in Africans, the above comparison models in LEPR rs1137101 and rs1137100 polymorphisms were all associated with decreased breast cancer risk rather than increased breast cancer risk after inspection of the ORs and 95 % CIs. Second, the P value of Cochran’s Q statistic was used to investigate the degree of heterogeneity between the studies in the meta-analysis. The authors suggested that a P value of more than the nominal level of 0.05 for the Q statistic

Is Usual Dietary Pattern Related to the Risk of Developing Breast Cancer?

Dietary patterns capture total diet providing a more comprehensive understanding of the effect of diet on chronic disease risk. Dietary patterns have been associated with several chronic diseases, including cardiovascular disease and selected cancers; however, the association with breast cancer remains unclear. The objective of this review was to examine critically the most recent literature on dietary patterns and breast cancer and report on current results, new developments, and future directions. Seven case-control and cohort studies from multiple countries have been published during the previous year (2011-2012). Many have analyzed a posteriori dietary patterns via factor and principal component analysis. Whereas results remain mixed, the majority of studies indicate healthier patterns decrease breast cancer risk, although patterns higher in meat and alcohol increase risk. Future studies that examine the associations between diet and tumor subtypes and collect dietary data at younger ages and, if possible, longitudinally would be beneficial.

Mediterranean Dietary Pattern and Risk of Breast Cancer

BackgroundA Mediterranean diet has a recognized beneficial effect on health and longevity, with a protective influence on several cancers. However, its association with breast cancer risk remains unclear.ObjectiveWe aimed to investigate whether adherence to a Mediterranean dietary pattern influences breast cancer risk.DesignThe Swedish Women’s Lifestyle and Health cohort study includes 49,258 women aged 30 to 49 years at recruitment in 1991–1992. Consumption of foods and beverages was measured at enrollment using a food frequency questionnaire. A Mediterranean diet score was constructed based on the consumption of alcohol, vegetables, fruits, legumes, cereals, fish, the ratio of unsaturated to saturated fat, and dairy and meat products. Relative risks (RR) for breast cancer and specific tumor characteristics (invasiveness, histological type, estrogen/progesterone receptor status, malignancy grade and stage) associated with this score were estimated using Cox regression controlling for potential confounders.Results1,278 incident breast cancers were diagnosed. Adherence to a Mediterranean dietary pattern was not statistically significantly associated with reduced risk of breast cancer overall, or with specific breast tumor characteristics. A RR (95% confidence interval) for breast cancer associated with a two-point increment in the Mediterranean diet score was 1.08 (1.00–1.15) in all women, and 1.10 (1.01–1.21) and 1.02 (0.91–1.15) in premenopausal and postmenopausal women, respectively. When alcohol was excluded from the Mediterranean diet score, results became not statistically significant.ConclusionsAdherence to a Mediterranean dietary pattern did not decrease breast cancer risk in this cohort of relatively young women.

Higher Blood 25(OH)D Level May Reduce the Breast Cancer Risk: Evidence from a Chinese Population Based Case-Control Study and Meta-Analysis of the Observational Studies

Experimental data suggest a protective effect of vitamin D on breast cancer; however, epidemiologic results remain inclusive. With a Chinese population-based case-control study and meta-analysis of the observational studies, we here systematically evaluated the association of blood 25(OH)D level and breast cancer risk. With 593 breast cancer cases and 580 cancer-free controls from Shanghai, China, we found that 80% of the normal women had severe vitamin D deficiency (less than 20 ng/mL) and 15.2% had mild deficiency (20 to 30 ng/mL) and only 4.8% of women had sufficient vitamin D level (>30 ng/mL) while the proportion was 96.1%, 3.2% and 0.7% respectively for the breast cancer patients. Compared to those with the lowest quartile of plasma 25(OH)D level, women with highest quartile 25(OH)D level showed a significant decreased breast cancer risk (Q4 vs.Q1: OR = 0.10, 95% CI = 0.06–0.15) and every 1 ng/ml increment of plasma 25(OH)D level led to a 16% lower odds of breast cancer (OR = 0.84, 95% CI = 0.81–0.87; P<0.001). From the meta-analysis of the observational studies, we found that women with highest quantile of blood 25(OH)D level was associated with a significantly reduced breast cancer risk compared to those with lowest quantile of blood 25(OH)D level for the 11 nested case-control and retrospective studies (pooled OR = 0.86, 95% CI = 0.75–1.00) and 10 case-control studies (7 population based, OR = 0.35, 95% CI = 0.24–0.52; 3 hospital based, OR = 0.08, 95% CI = 0.02–0.33). These results suggest that vitamin D may have a chemo-preventive effect against breast cancer.

Association of 8q24 rs13281615A &gt; G polymorphism with breast cancer risk: evidence from 40,762 cases and 50,380 controls

The association between a single nucleotide polymorphism rs13281615A > G located in the 8q24 and breast cancer risk is still controversial and ambiguous. Hence, we performed a more convincing and precise estimation of the relationship between 8q24 and breast cancer by meta-analyzing the currently available evidence from literature. PubMed, Ovid, Medline, and Web of Science databases were searched. A total of 10 publications containing 11 studies including 40,762 cases and 50,380 controls were identified. Crude odds ratio with 95 % confidence interval was used to assess the strength of association. We observed that the 8q24 rs13281615A > G polymorphism was significantly correlated with breast cancer risk when all studies were pooled into the meta analysis. In the stratified analysis by ethnicity, significantly increased risks were also found among Caucasians for all genetic models. For mixed ethnicities, significantly increased risks were found for all genetic models except for the allele contrast model. However, no significantly increased risk was found among Africans for all genetic models. Interestingly, when stratified by BRCA1 mutation carriers status, significantly decreased breast cancer risk was found for allele contrast model. But significantly increased breast cancer risk was found in the BRCA2 mutation carriers for all genetic models except for the recessive model. There was no evidence for significant association between 8q24 rs13281615A > G polymorphism and breast cancer risk in BRCA1 and BRCA2 positive cohort in all comparable models. In conclusion, this meta-analysis suggests that the 8q24 rs13281615A > G polymorphism is a low-penetrant risk factor for developing breast cancer but may not be in Africans.

Current Resources for Evidence‐Based Practice January/February 2013

Current Resources for Evidence‐Based Practice January/February 2013

Mammographic Density and Risk of Breast Cancer

The radiographic appearance of the breast on mammography varies among women, and reflects variations in breast tissue composition and the different X-ray attenuation characteristics of these tissues. Fat is radiologically lucent and appears dark on a mammogram. Connective and epithelial tissues are radiologically dense and appear light. These variations in appearance are commonly described as the percentage of the breast image that is radiologically dense, or as percent mammographic density (PMD). There is now extensive evidence that PMD is a risk factor for breast cancer, with a 4- to 6-fold gradient in risk between women with 75% or more PMD compared with those with 10% or less. However, the accuracy of risk prediction in individual women is modest. The extent of PMD is associated inversely with greater age, parity, and weight, and is reduced by the menopause and by tamoxifen. PMD is positively associated with greater height, a family history of breast cancer, and is increased by combined hormone therapy. The relative risk associated with density is substantially larger than the relative risk of breast cancer associated with a family history of the disease or any of the menstrual and reproductive risk factors. It is estimated that the risks of breast cancer attributable to density of 50% or more may be 16% for all breast cancers. Although combined hormone therapy and tamoxifen respectively increase a decrease both PMD and breast cancer risk, there is as yet insufficient evidence to use PMD as a surrogate marker for breast cancer.

Abstract P5-10-15: Genetic variants located in beta2 adrenergic receptor gene (ADRB2) and miRNA let-7 binding site alter breast cancer susceptibility: a case control analysis

Abstract Previous studies have shown that a potential association may exist between risk of breast cancer and polymorphisms in the beta-adrenergic receptor gene. ADRB2 is a target for miRNA let-7 and it is reported that low let-7 expression probably increases risk of breast cancer. In this study, we investigated the relationship between genetic variants located in alpha2 and beta2 adrenergic receptor genes and miRNA let-7 binding sites with breast cancer risk in benign mammary disease and sporadic breast cancer. We assessed frequency distributions of these variants in 741 patients with histologically confirmed breast cancer and 315 controls with benign mammary disease. We initially demonstrated that rs1042713, located in ADRB2 and rs11292, located in miRNA let-7 binding site were associated with susceptibility to breast cancer. A significant association was observed between GG, AG+GG genotype compared to AA genotype of SNP rs1042713 and a decreased breast cancer risk (adjusted OR = 0.79, 95%CI: 0.64–0.97, p = 0.025; adjusted OR = 0.72, 95%CI: 0.54–0.96, p = 0.028). We also found a significant association between TC, TC+CC genotype compared to TT genotype of SNP rs11292 and an increased breast cancer risk (adjusted OR = 1.44, 95%CI: 1.01–2.06, p = 0.044; adjusted OR = 1.43, 95%CI: 1.01–2.02, p = 0.044). The allele of G of SNP rs1042713 was associated with a decreased risk of breast cancer (OR = 0.79, 95%CI: 0.66–0.96, p = 0.018). Taken together, our study demonstrated that genetic variants located in ADRB2 and miRNA let-7 binding site could alter breast cancer risk. Keywords: ADRB2 gene, miRNA let-7, polymorphism, breast cancer Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-10-15.

Dual association between polyphenol intake and breast cancer risk according to alcohol consumption level: a prospective cohort study

Studies of the association between polyphenols dietary intake and breast cancer risk have been limited due to the lack of detailed food composition tables. In addition, none has examined this association according to alcohol intake, despite the facts that alcohol is an established risk factor for breast cancer and that the contribution of alcoholic beverages to polyphenol intake varies according to the level of alcohol consumption. Our objectives were (1) to estimate the associations between breast cancer risk and a wide range of dietary polyphenols using the recently published Phenol-Explorer database; and (2) to evaluate if/how alcohol intake modulates these relationships. 4,141 women from the SU.VI.MAX prospective cohort were followed from 1994 to 2007 (median followup: 12.6 years); 152 developed a first incident invasive primary breast cancer. Dietary intakes were assessed by repeated 24-h records. The Phenol-Explorer database was used to estimate polyphenol intake. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95 % confidence intervals (CIs) for quartiles of polyphenol intake. Analyses were stratified by median alcohol intake (< vs. ≥ 6.5 g/d). In non-to-low alcohol drinkers, intakes of some classes of polyphenols were associated with decreased breast cancer risk: hydroxybenzoic acids (HR(Q4vsQ1) = 0.38, 95 % CI: 0.17-0.86, P (trend) = 0.005), flavonoids (0.35, 0.17-0.75, P (trend) = 0.02), flavonols (0.36, 0.18-0.74, P (trend) = 0.002), catechins (0.48, 0.22-1.05, P (trend) = 0.02), theaflavins (0.42, 0.19-0.93, P (trend) = 0.02), and proanthocyanidins (0.39, 0.18-0.84, P (trend) = 0.02). In contrast, in women with higher alcohol use, intakes of hydroxybenzoic acids (2.28, 1.16-4.49, P (trend) = 0.04), flavonoids (2.46, 1.23-4.92, P (trend) = 0.01), anthocyanins (2.94, 1.32-6.53, P (trend) = 0.01), catechins (2.28, 1.19-4.36, P (trend) = 0.02), and proanthocyanidins (2.98, 1.40-6.33, P (trend) = 0.006) were associated with increased breast cancer risk. In conclusion, this prospective study suggests that several classes of polyphenols could potentially contribute to breast cancer prevention among non-to-low alcohol drinkers, but some may increase breast cancer risk among women with higher alcohol intake.

Three novel functional polymorphisms in the promoter of FGFR2 gene and breast cancer risk: a HuGE review and meta-analysis

Published data on the association between three novel functional polymorphisms (rs11200014, rs2981579, and rs2981578) in the promoter of FGFR2 gene and breast cancer risk are inconclusive. The aim of this human genome epidemiology review and meta-analysis was to derive a more precise estimation of the relationship. A literature search of Pubmed, Embase, Web of science, and CBM databases from inception through July 2012 was conducted. Seventeen studies were included with a total of 21,742 breast cancer cases and 31,125 healthy controls. Crude odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of association in allele model, dominant model, recessive model, homozygous model, and heterozygous model. When all the eligible studies were pooled into the meta-analysis, remarkable associations between the rs11200014 (A>G) polymorphism and breast cancer risk were detected in Caucasians (G vs. A: OR = 1.28, 95 % CI: 1.21-1.35; GG/AG vs. AA: OR = 1.32, 95 % CI: 1.18-1.48), but not in Asians and Africans. In addition, there were statistically significant associations between the rs2981579 (G>A) polymorphism and increased risk of breast cancer risk in all ethnicities (A vs. G: OR = 1.20, 95 % CI: 1.11-1.29; AA/GA vs. GG: OR = 1.32, 95 % CI: 1.18-1.48; AA vs. GG: OR = 1.67, 95 % CI: 1.55-1.81), including Caucasians, Asians, and Africans. However, the TT genotype of rs2981578 (C>T) polymorphism might decrease breast cancer risk (TT vs. OR = 0.55, 95 % CI: 0.38-0.79; TT vs. CC: OR = 0.51, 95 % CI: 0.35-0.76; TT vs. CT: OR = 0.58, 95 % CI: 0.40-0.85), especially among Asians. Results from the current meta-analysis indicates that three novel functional polymorphisms (rs11200014, rs2981579, and rs2981578) in the promoter of FGFR2 gene are associated with breast cancer susceptibility and might be a potential biomarkers for breast cancer risk.