Circulating Hormones and Mammographic Density in Premenopausal Women

Prior research suggests that several endogenous hormones in premenopausal women are associated with breast cancer risk; however, few studies have evaluated associations of endogenous hormones with mammographic density (MD) in premenopausal women. We conducted a cross-sectional study of plasma hormone levels in relation to MD among 634 cancer-free premenopausal women in the Nurses’ Health Study II. We measured percent MD from screening mammograms using a computer-assisted method. We assayed estradiol, estrone, and estrone sulfate in blood samples timed in early follicular and mid-luteal phases of the menstrual cycle as well as testosterone, androstenedione, progesterone, dehydroepiandrosterone (DHEA), DHEA sulfate, sex hormone–binding globulin (SHBG), and anti-Müllerian hormone in luteal or untimed samples. We used multivariable linear regression to quantify the association of %MD with quartiles of each hormone, adjusting for age, body mass index, and breast cancer risk factors. Women in the highest quartile of follicular estradiol levels had significantly greater %MD compared to those in the lowest quartile [difference, 6.7 percentage points; 95% confidence interval (CI) 2.2, 11.3; p-trend?<?0.001]. Similar associations were observed for follicular free estradiol but not luteal-phase estradiol. Also, women in the top (vs. bottom) quartile of free testosterone had significantly lower %MD (difference, ??4.7; 95% CI ??8.7, ??0.8; p-trend?=?0.04). Higher SHBG was significantly associated with higher percent MD (difference, 4.8; 95% CI 1.1, 8.6; p-trend?=?0.002). Percent MD was not strongly associated with other measured hormones. Results were similar in analyses that excluded women with anovulatory cycles. Our findings suggest that follicular estradiol and SHBG may play an important role in premenopausal percent MD.     

Detection of elevated plasma levels of epidermal growth factor receptor before breast cancer diagnosis among hormone therapy users

Applying advanced proteomic technologies to prospectively collected specimens from large studies is one means of identifying preclinical changes in plasma proteins that are potentially relevant to the early detection of diseases such as breast cancer. We conducted 14 independent quantitative proteomics experiments comparing pooled plasma samples collected from 420 estrogen receptor-positive (ER(+)) breast cancer patients ≤17 months before their diagnosis and matched controls. Based on the more than 3.4 million tandem mass spectra collected in the discovery set, 503 proteins were quantified, of which 57 differentiated cases from controls with a P value of <0.1. Seven of these proteins, for which quantitative ELISA assays were available, were assessed in an independent validation set. Of these candidates, epidermal growth factor receptor (EGFR) was validated as a predictor of breast cancer risk in an independent set of preclinical plasma samples for women overall [odds ratio (OR), 1.44; P = 0.0008] and particularly for current users of estrogen plus progestin (E + P) menopausal hormone therapy (OR, 2.49; P = 0.0001). Among current E + P users, the EGFR sensitivity for breast cancer risk was 31% with 90% specificity. Whereas the sensitivity and specificity of EGFR are insufficient for a clinically useful early detection biomarker, this study suggests that proteins that are elevated preclinically in women who go on to develop breast cancer can be discovered and validated using current proteomic technologies. Further studies are warranted to examine the role of EGFR and to discover and validate other proteins that could potentially be used for early detection of breast cancer.     

Associations of one-carbon metabolism-related gene polymorphisms with breast cancer risk are modulated by diet,being higher when adherence to the Mediterranean dietary pattern is low

Purpose

Breast cancer is more likely attributed to a combination of genetic variations and lifestyle factors. Both one-carbon metabolism and diet-related factors could interfere with the carcinogenesis of breast cancer (BC), but whether diet consumed underlie a specific metabolism pathway could influence the impact of genetic variants on breast cancer risk remains equivocal.

Methods

A case–control study of the Chinese female population (818 cases, 935 controls). 13 SNPs in eight one-carbon metabolism-related genes (MTHFD1, TYMS, MTRR, MAT2B, CDO1, FOLR1, UNG2, ADA) were performed. Diet was assessed by a validated food-frequency questionnaire. We examined the associations of the adherence to the Mediterranean dietary pattern (MDP) and single-nucleotide polymorphisms (SNPs) of one-carbon metabolism with breast cancer risk. We constructed an aggregate polygenic risk score (PRS) to test the additive effects of genetic variants and analyzed the gene–diet interactions.

Results

High adherence (highest quartile) to the MDP decreased the risk of breast cancer among post- but not premenopausal women, respectively (OR?=?0.54, 95% CI?=?0.38 to 0.78 and 0.90, 0.53 to 1.53). Neither of the polymorphisms or haplotypes was associated with breast cancer risk, irrespective of menopause. However, a high PRS (highest quartile) was associated with more than a doubling risk in both post- and premenopausal women, respectively (OR?=?1.95, 95% CI?=?1.32 to 2.87 and 2.09, 1.54 to 2.85). We found a gene–diet interaction with adherence to the MDP for aggregate PRS (P-interaction?=?0.000) among postmenopausal women. When adherence to the MDP was low (<?median), carries with high PRS (highest quartile) had higher BC risk (OR?=?2.80, 95% CI?=?1.55 to 5.07) than low PRS (lowest quartile), while adherence to the MDP was high (≥ median), the association disappeared (OR?=?1.57, 95% CI?=?0.92 to 2.66).

Conclusion

High adherence to the MDP may counteract the genetic predisposition associated with one-carbon metabolism on breast cancer risk in postmenopausal women.

     

The polymorphism of EGFR 142285G > A exerts no risk effect on breast cancer

The association between the epidermal growth factor receptor (EGFR) 142285G?>?A polymorphism and the susceptibility to breast cancer is unclear. We conducted a meta-analysis of all published studies to estimate the association of EGFR 142285G?>?A polymorphism and breast cancer risk. Systematic computerized searching of the PubMed, Web of Science, and Wanfang databases was performed for relevant publications. Overall, there were three eligible case–control studies with 1,360 cases and 1,522 controls included into our study. The pooled ORs showed that the EGFR 142285G?>?A variant genotypes did not increase or decrease the risk of breast cancer under the following gene models: A vs. G, OR?=?1.07, 95 % CI 0.96–1.19, P _OR?=?0.240; AA vs. GG, OR?=?1.14, 95 % CI 0.91–1.42, P _OR?=?0.239; GA vs. GG, OR?=?0.99, 95 % CI 0.83–1.17, P _OR?=?0.892; GA?+?AA vs. GG, OR?=?1.03, 95 % CI 0.87–1.21, P _OR?=?0.727; AA vs. GG?+?GA, OR?=?1.17, 95 % CI 0.97–1.42, P _OR?=?0.096. The between-study heterogeneity was not significant among all studies. The current meta-analysis showed no evidence for significant association between EGFR 142285G?>?A polymorphism and breast cancer risk. Subsequent studies with large sample size are needed for further elucidation.     

Foxp3 promoter polymorphism (rs3761548) in breast cancer progression: a study from India

Breast cancer is the most common female neoplasm that drives the transformation of normal mammary epithelial cells into highly malignant derivatives. Forkhead Box Protein3 (Foxp3), a tumor suppressor/immunomodulatory gene, which controls the function of Treg cells and oncogenes is down regulated in breast cancer. The main aim of the present study is to evaluate the potential influence of Foxp3-3279 C>A polymorphism (rs3761548) and -2383 C>T polymorphism (rs3761549) in 202 breast cancer patients and 130 normal healthy women of Indian origin. The genotypes were determined using ARMS-PCR for rs3761548 and PCR-RFLP method for rs3761549 using specific primers. The results revealed lack of association of these two polymorphisms with breast cancer susceptibility. However, with respect to AA genotype of rs3761548, we found highly significant association with the advanced stage (T3-4) of the tumor (OR?=?3.90; 95 % confidence interval (CI)?=?1.56–9.70; p?=?0.03). Stratified data also revealed an association of homozygous mutant genotype with advanced stage of tumor in premenopausal women (OR?=?4.56; 95 % CI?=?1.07–19.38; p?=?0.04) with disease duration of <6 months (OR?=?6.10; 95 % CI?=?1.80–20.50; p?=?0.002) suggestive of modulating effect of rs3761548 in tumor progression. We conclude that Foxp3 rs37161548 has a potential to be a polymorphic marker for tumor progression in premenopausal breast cancer patients in Indian women.     

Blood arsenic levels and the risk of familial breast cancer in Poland

Arsenic is recognized as a potent carcinogen at high concentrations, but the relationship between environmental arsenic and breast cancer risk has not well been studied. Most research has focused on the effect of arsenic in populations with high endemic exposure, and not in populations with arsenic levels within normal limits. We sought to determine if blood arsenic levels predict the risk of breast and other cancers risk among women in northern Poland. The cohort consisted of 1,702 healthy women, aged 40 and above, identified between 2010 and 2017. Blood arsenic level was determined by inductively coupled plasma mass spectrometry. After an average of 4.5 years of follow-up (range 0.7–7.3 years), there were 110 incident cases of cancer diagnosed in the cohort, including 68 cases of breast cancer. Women in the highest quartile of arsenic had a highly significant 13-fold increased risk of developing breast cancer, compared to women in the lowest quartile (hazard ratio [HR] = 13.2; 95% confidence interval [CI] 4.02–43.0). Results were similar for arsenic and all incident cancers (HR quartile 4 vs. quartile 1 = 13.3; 95% CI 4.78–37.0). If confirmed, our study suggests that the blood arsenic level may be a useful predictive marker of cancer risk in women.     

Lower Circulating Androgens Are Associated with Overall Cancer Risk and Prostate Cancer Risk in Men Aged 25–84 Years from the Busselton Health Study

Androgens, notably testosterone (T), have been implicated in development of several common cancers and prostate cancer; however, precise mechanisms remain unclear. This study assessed prospective associations of serum T, dihydrotestosterone (DHT) and estradiol (E2) with overall cancer (excluding skin cancer), prostate, colorectal and lung cancer risk in 1574 community-dwelling men aged 25–84 years. Sex hormones were assayed using mass spectrometry and men were followed for 20 years with outcomes ascertained using data linkage. Over 20 years, there were 289, 116, 48 and 22 men who developed any cancer, prostate cancer, colorectal cancer and lung cancer, respectively. Androgens in the lowest quartile were associated with an increased overall cancer risk (HR?=?1.36, 95% CI 1.05–1.76, p?=?0.020 for T; and HR?=?1.30, 95% CI 1.00–1.69, p?=?0.049 for DHT comparing the lowest vs other quartiles). T in the lowest quartile was associated with an increased risk of prostate cancer (HR?=?1.53, 95% CI 1.02–2.29, p?=?0.038 comparing the lowest vs other quartiles). The association between androgens and overall cancer risk remained similar after excluding prostate cancer outcomes; however, results were not significant. There were no associations of T, DHT or E2 with colorectal or lung cancer risk; however, LH in the highest quartile was associated with an increased risk of lung cancer (HR?=?4.55, 95% CI 1.70–12.19, p?=?0.003 for the highest vs other quartiles). Whether T is a biomarker of poor health in men with any cancer or prostate cancer requires further confirmation as does the nature and mechanism of the association of a high LH with future lung cancer.     

Discovery and preliminary confirmation of novel early detection biomarkers for triple-negative breast cancer using preclinical plasma samples from the Women’s Health Initiative observational study

Triple-negative breast cancer is a particularly aggressive and lethal breast cancer subtype that is more likely to be interval-detected rather than screen-detected. The purpose of this study is to discover and initially validate novel early detection biomarkers for triple-negative breast cancer using preclinical samples. Plasma samples collected up to 17 months before diagnosis from 28 triple-negative cases and 28 matched controls from the Women’s Health Initiative Observational Study were equally divided into a training set and a test set and interrogated by a customized antibody array. Data were available on 889 antibodies; in the training set, statistically significant differences in case versus control signals were observed for 93 (10.5 %) antibodies at p < 0.05. Of these 93 candidates, 29 were confirmed in the test set at p < 0.05. Areas under the curve for these candidates ranged from 0.58 to 0.79. With specificity set at 98 %, sensitivity ranged from 4 to 68 % with 20 candidates having a sensitivity ≥20 % and 6 having a sensitivity ≥40 %. In an analysis of KEGG gene sets, the pyrimidine metabolism gene set was upregulated in cases compared to controls (p = 0.004 in the testing set) and the JAK/Stat signaling pathway gene set was downregulated (p = 0.003 in the testing set). Numerous potential early detection biomarkers specific to triple-negative breast cancer in multiple pathways were identified. Further research is required to followup on promising candidates in larger sample sizes and to better understand their potential biologic importance as our understanding of the etiology of triple-negative breast cancer continues to grow.     

Relation of Serum Estrogen Metabolites with Terminal Duct Lobular Unit Involution Among Women Undergoing Diagnostic Image-Guided Breast Biopsy

Higher levels of circulating estrogens and estrogen metabolites (EMs) have been associated with higher breast cancer risk. In breast tissues, reduced levels of terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini per TDLU, have also been linked to elevated breast cancer risk. However, it is unknown whether reduced TDLU involution mediates the risk associated with circulating EMs. In a cross-sectional analysis of 94 premenopausal and 92 postmenopausal women referred for clinical breast biopsy at an academic facility in Vermont, we examined the associations of 15 EMs, quantified using liquid chromatography-tandem mass spectrometry, with the number of TDLUs and acini count/TDLU using zero-inflated Poisson regression with a robust variance estimator and ordinal logistic regression models, respectively. All analyses were stratified by menopausal status and adjusted for potential confounders. Among premenopausal women, comparing the highest vs. the lowest tertiles, levels of unconjugated estradiol (risk ratio (RR)?=?1.74, 95 % confidence interval (CI)?=?1.06–2.87, p trend?=?0.03), 2-hydroxyestrone (RR?=?1.74, 95 % CI?=?1.01–3.01, p trend?=?0.04), and 4-hydroxyestrone (RR?=?1.74, 95 % CI?=?0.99–3.06, p trend?=?0.04) were associated with significantly higher TDLU count. Among postmenopausal women, higher levels of estradiol (RR?=?2.09, 95 % CI?=?1.01–4.30, p trend?=?0.04) and 16α-hydroxyestrone (RR?=?2.27, 95 % CI?=?1.29–3.99, p trend?=?0.02) were significantly associated with higher TDLU count. Among postmenopausal women, higher levels of EMs, specifically conjugated estrone and 2- and 4-pathway catechols, were also associated with higher acini count/TDLU. Our data suggest that higher levels of serum EMs are generally associated with lower levels of TDLU involution.     

Association of p73 G4C14-A4T14 polymorphisms with genetic susceptibilities to breast cancer: a case–control study

The aim of this study was to evaluate the association of p73 G4C14-A4T14 polymorphisms with susceptibility to breast cancer in Chongqing women of Han Nationality in China. In a case?Ccontrol study, single-nucleotide polymorphisms of p73 G4C14-A4T14 at exon 2 were genotyped by Sequenom MassArray^? iPLEX GOLD System in 170 patients with breast cancer and 178 healthy controls. Data were analyzed via t test, Chi-square test, and logistic regression analysis. The distribution of p73 genotypes and allelotypes had no significant difference between patients with breast cancer and healthy controls (??²?=?2.750, P?=?0.253; ??²?=?2.195, P?=?0.138). More risk of developing triple negative breast cancer (TNBC) was found in the individuals who carried with GC/GC genotype than individuals carried with GC/AT and AT/AT genotypes (OR?=?2.99; 95?% CI, 1.30?C6.89; P?=?0.010). p73 G4C14-A4T14 polymorphisms are closely associated with the increased risk for TNBC in Chongqing women of Han Nationality in China; GC/GC genotype is susceptible genotype for TNBC in Chongqing women of Han Nationality in China. The patients with breast cancer who carried with GC/GC genotype may have bad prognosis. Additional larger studies are required to confirm these findings.     

Knowledge and Prevention Practices Before Breast Cancer Diagnosis in a Cross-Sectional Study Among Survivors: Impact on Patients’ Involvement in the Decision Making Process

Disparities exist in breast cancer knowledge and education, which tend to influence symptom interpretation and decision to seek screening/care. The present project describes a cohort of women’s experiences, knowledge, and health behavior prior to and after a diagnosis of breast cancer. It also studies how knowledge and demographic factors are associated with level of involvement participants had in the treatment of their breast cancer. Women >18 years who have been diagnosed and treated for breast cancer within 10 years were recruited in Pittsburgh, PA, through the Healthy People Cohort Registry, a database of volunteers from the community, and Brooklyn, NY, through the American Cancer Society breast cancer survivor database. Subsequent to institutional ethics approval, a questionnaire was administered by mail and through an electronic interactive format. The study included 124 breast cancer survivors, one-quarter of whom were of African ancestry. Roughly half of the women indicated that their overall knowledge of breast cancer was limited before diagnosis; no significant association between overall knowledge before diagnosis and stage at diagnosis or an active role of the patient in treatment choices was observed. Two-third of the women reported using personal research on internet, books, and other media to increase knowledge on breast cancer after diagnosis; the improvement of knowledge was associated with an active role in therapy choice. White women’s self report of breast cancer knowledge prior to diagnosis was higher than that of women of African origin (p?=?0.03); the latter experienced more delays in getting results about the diagnosis (p?=?0.002), in starting treatment (p?=?0.03), and in having treatment available at local facilities (p?=?0.007) than white women. White women were more likely to improve their knowledge through their own research (p?=?0.08) and through the contribution of their physician (p?=?0.06) than women of African origin.There is still a need for addressing breast cancer knowledge among black women, and improvement in physician emotional support and in their contribution to the patient’s knowledge is necessary. These efforts may have a positive impact on breast cancer knowledge among black women in the US.     

Promoting Breast Cancer Screening Among Asian American Women: the Asian Grocery Store-Based Cancer Education Program

Asian American women's historically low breast cancer mortality rate has remained constant as rates decreased for all other races. From 2000 to 2004, a randomized controlled trial explored the Asian grocery store-based breast cancer education program's impact on Chinese, Filipino, Korean, and Vietnamese women (n?=?1,540). Women aged 40 and older and non-adherent for annual screening mammograms were more likely to schedule a mammogram after receiving the breast cancer education program than women randomized to the prostate cancer program (X ²?=?3.85, p?=?0.05). With the right program ingredients, late adopters of breast cancer screening can be prompted to change.     

Prospective validation of the NCI Breast Cancer Risk Assessment Tool (Gail Model) on 40,000 Australian women

Background

There is a growing interest in delivering more personalised, risk-based breast cancer screening protocols. This requires population-level validation of practical models that can stratify women into breast cancer risk groups. Few studies have evaluated the Gail model (NCI Breast Cancer Risk Assessment Tool) in a population screening setting; we validated this tool in a large, screened population.

Methods

We used data from 40,158 women aged 50–69?years (via the lifepool cohort) participating in Australia’s BreastScreen programme. We investigated the association between Gail scores and future invasive breast cancer, comparing observed and expected outcomes by Gail score ranked groups. We also used machine learning to rank Gail model input variables by importance and then assessed the incremental benefit in risk prediction obtained by adding variables in order of diminishing importance.

Results

Over a median of 4.3?years, the Gail model predicted 612 invasive breast cancers compared with 564 observed cancers (expected/observed (E/O)?=?1.09, 95% confidence interval (CI) 1.00–1.18). There was good agreement across decile groups of Gail scores (χ²?=?7.1, p?=?0.6) although there was some overestimation of cancer risk in the top decile of our study group (E/O?=?1.65, 95% CI 1.33–2.07). Women in the highest quintile (Q5) of Gail scores had a 2.28-fold increased risk of breast cancer (95% CI 1.73–3.02, p?<?0.0001) compared with the lowest quintile (Q1). Compared with the median quintile, women in Q5 had a 34% increased risk (95% CI 1.06–1.70, p?=?0.014) and those in Q1 had a 41% reduced risk (95% CI 0.44–0.79, p?<?0.0001). Similar patterns were observed separately for women aged 50–59 and 60–69?years. The model’s overall discrimination was modest (area under the curve (AUC) 0.59, 95% CI 0.56–0.61). A reduced Gail model excluding information on ethnicity and hyperplasia was comparable to the full Gail model in terms of correctly stratifying women into risk groups.

Conclusions

This study confirms that the Gail model (or a reduced model excluding information on hyperplasia and ethnicity) can effectively stratify a screened population aged 50–69 years according to the risk of future invasive breast cancer. This information has the potential to enable more personalised, risk-based screening strategies that aim to improve the balance of the benefits and harms of screening.

     

Glycemic Load,Glycemic Index,and the Risk of Breast Cancer Among Mexican Women

Objective: The amount and composition of dietary carbohydrates is a major determinant of postprandial blood glucose and insulin, and risk of breast cancer has been positively associated with plasma levels of insulin and insulin-like growth factor 1. We sought to evaluate dietary glycemic load (GL) and overall glycemic index (GI) in relation to breast cancer risk in Mexican women. Methods: We examined dietary GL and overall GI and breast cancer risk among 475 women with histologically-confirmed breast cancer and a random sample of 1391 women from Mexico City households. Diet was assessed using a food frequency questionnaire adapted to the Mexican population. Results: The multivariate adjusted or for all women comparing the highest quartile of dietary GL with the lowest quartile was 1.62 (95% CI 1.13–2.32; p-test for trend = 0.02) with a significant trend. In postmenopausal women, the multivariate adjusted or comparing the extreme quartiles was 2.18 (95% CI 1.34–3.55; p-test for trend=0.005). Overall GI was not significantly associated with risk of breast cancer. Conclusion: High intake of rapidly absorbed carbohydrate appears to play an important role in the risk of breast cancer in Mexican women.     

Does mammographic density mediate risk factor associations with breast cancer? An analysis by tumor characteristics

Background

Though mammographic density (MD) has been proposed as an intermediate marker of breast cancer risk, few studies have examined whether the associations between breast cancer risk factors and risk are mediated by MD, particularly by tumor characteristics.

Methods

Our study population included 3392 cases (1105 premenopausal) and 8882 (3192 premenopausal) controls from four case–control studies. For established risk factors, we estimated the percent of the total risk factor association with breast cancer that was mediated by percent MD (secondarily, by dense area and non-dense area) for invasive breast cancer as well as for subtypes defined by the estrogen receptor (ER+/ER?), progesterone receptor (PR+/PR?), and HER2 (HER2+/HER2?). Analyses were conducted separately in pre- and postmenopausal women.

Results

Positive associations between prior breast biopsy and risk of invasive breast cancer as well as all subtypes were partially mediated by percent MD in pre- and postmenopausal women (percent mediated?=?11–27%, p?≤?0.02). In postmenopausal women, nulliparity and hormone therapy use were positively associated with invasive, ER+?, PR+?, and HER2? breast cancer; percent MD partially mediated these associations (percent mediated?≥?31%, p?≤?0.02). Further, among postmenopausal women, percent MD partially mediated the positive association between later age at first birth and invasive as well as ER+?breast cancer (percent mediated?=?16%, p?≤?0.05).

Conclusion

Percent MD partially mediated the associations between breast biopsy, nulliparity, age at first birth, and hormone therapy with risk of breast cancer, particularly among postmenopausal women, suggesting that these risk factors at least partially influence breast cancer risk through changes in breast tissue composition.

     

Plasma free 25-hydroxyvitamin D,vitamin D binding protein,and risk of breast cancer in the Nurses’ Health Study II

Purpose

Prior prospective studies, including our own, have evaluated total plasma 25-hydroxyvitamin D [25(OH)D] and breast cancer risk with inconsistent results. However, recent studies suggest that some vitamin D functions may be more relevant to the unbound (free) fraction of 25(OH)D. Vitamin D binding protein (DBP) influences the free 25(OH)D levels and thus possibly the biological activities of vitamin D.

Methods

We conducted a case–control study nested within the Nurses’ Health Study II to evaluate the association of plasma free 25(OH)D and DBP with breast cancer risk in predominantly premenopausal women. Plasma samples were assayed for 25(OH)D and DBP in 584 case–control pairs. Free 25(OH)D levels were calculated based on plasma levels of total 25(OH)D, DBP, and a constant value representing average albumin levels. Conditional logistic regression was used to estimate relative risks (RRs) and 95 % confidence intervals (CIs).

Results

We found no association between plasma calculated free 25(OH)D and risk of breast cancer overall (highest vs. lowest quartile RR 1.21, 95 % CI 0.83–1.77, trend test p value = 0.50). No association was observed for plasma DBP as well (highest vs. lowest quartile RR 0.95, 95 % CI 0.67–1.36, trend test p value = 0.96). Results were similar by tumor hormone receptor status. Neither the total nor the calculated free 25(OH)D and breast cancer association substantially varied by plasma DBP levels.

Conclusions

Our study does not support an important role of either calculated circulating free 25(OH)D or circulating DBP levels in breast cancer risk among predominantly premenopausal women.     

Ethnic Differences in Breast Cancer Prevention Information-Seeking Among Rural Women: Will Provider Mobile Messages Work?

Although growing research supports cancer survivor information-seeking, little is known about breast cancer prevention information-seeking among women. The purpose of the study was to examine differences in breast cancer risk factor knowledge, information sources, and desired mobile messages among Hispanic and non-Hispanic rural women. Women were recruited to complete a survey at an imaging center during a mammography screening visit. A total of 156 women (mean age?=?61, SD?=?12.07) completed the survey. Breast cancer risk factor knowledge was significantly higher for non-Hispanic women compared to Hispanic women (p?=?.035). Television, magazines, and Internet were the most frequent information sources. Providers were the most frequent interpersonal information source. Nearly 87 % used cell phones and 47 % used texting. Hispanic women were more likely to desire breast cancer prevention cell voice messages (p?p?=?.001) compared to non-Hispanic women. No significant differences were found for text appointment reminders by ethnicity. Health educators and clinicians must promote mobile messages for Hispanics and non-Hispanics for mammography adherence, breast cancer prevention education, and best practices to manage screening appointments.     

Selenium and breast cancer risk: A prospective nested case–control study on serum selenium levels,smoking habits and overweight

Previous research has not been conclusive regarding the association between selenium (Se) and breast cancer. This study was conducted to clarify if there is an association between prediagnostic serum Se levels and breast cancer risk. A population based cohort, the Malmö Diet and Cancer Study, was used and linked with the Swedish cancer registry up to 31 December 2013. Our study included 1,186 women with breast cancer and an equal number of controls. Selenium levels were analysed from stored serum samples. The included individuals were divided into quartiles based on Se value and we compared breast cancer cases with controls using logistic regression yielding odds ratios (OR) with 95% confidence intervals. Serum Se was also analysed as a continuous variable regarding breast cancer risk. The analyses were adjusted for established risk factors and stratified on smoking status and body mass index (BMI). When comparing the highest Se quartile with the lowest, the adjusted OR for breast cancer was 0.98 (0.75–1.26). With selenium as a continuous variable the adjusted OR was 1.00 (1.00–1.01) per 10 ng/ml. When comparing the highest with the lowest Se quartile in women with BMI > 25 kg/m² the adjusted OR was 0.77 (0.53–1.14). We conclude that it is unlikely that prediagnostic serum selenium is overall associated with breast cancer risk and no modifying effect from BMI or smoking was seen.     

Polymorphisms in oxidative stress genes, physical activity, and breast cancer risk

Purpose

The mechanisms driving the physical activity–breast cancer association are unclear. Exercise both increases reactive oxygen species production, which may transform normal epithelium to a malignant phenotype, and enhances antioxidant capacity, which could protect against subsequent oxidative insult. Given the paradoxical effects of physical activity, the oxidative stress pathway is of interest. Genetic variation in CAT or antioxidant-related polymorphisms may mediate the physical activity–breast cancer association.

Methods

We investigated the main and joint effects of three previously unreported polymorphisms in CAT on breast cancer risk. We also estimated interactions between recreational physical activity (RPA) and 13 polymorphisms in oxidative stress-related genes. Data were from the Long Island Breast Cancer Study Project, with interview and biomarker data available on 1,053 cases and 1,102 controls.

Results

Women with ≥1 variant allele in CAT rs4756146 had a 23?% reduced risk of postmenopausal breast cancer compared with women with the common TT genotype (OR?=?0.77; 95?% CI?=?0.59–0.99). We observed two statistical interactions between RPA and genes in the antioxidant pathway (p?=?0.043 and 0.006 for CAT and GSTP1, respectively). Highly active women harboring variant alleles in CAT rs1001179 were at increased risk of breast cancer compared with women with the common CC genotype (OR?=?1.61; 95?% CI, 1.06–2.45). Risk reductions were observed among moderately active women carrying variant alleles in GSTP1 compared with women homozygous for the major allele (OR?=?0.56; 95?% CI, 0.38–0.84).

Conclusions

Breast cancer risk may be jointly influenced by RPA and genes involved in the antioxidant pathway, but our findings require confirmation.     

The associations between a polygenic score, reproductive and menstrual risk factors and breast cancer risk

We evaluated whether 13 single nucleotide polymorphisms (SNPs) identified in genome-wide association studies interact with one another and with reproductive and menstrual risk factors in association with breast cancer risk. DNA samples and information on parity, breastfeeding, age at menarche, age at first birth, and age at menopause were collected through structured interviews from 1,484 breast cancer cases and 1,307 controls who participated in a population-based case–control study conducted in three US states. A polygenic score was created as the sum of risk allele copies multiplied by the corresponding log odds estimate. Logistic regression was used to test the associations between SNPs, the score, reproductive and menstrual factors, and breast cancer risk. Nonlinearity of the score was assessed by the inclusion of a quadratic term for polygenic score. Interactions between the aforementioned variables were tested by including a cross-product term in models. We confirmed associations between rs13387042 (2q35), rs4973768 (SLC4A7), rs10941679 (5p12), rs2981582 (FGFR2), rs3817198 (LSP1), rs3803662 (TOX3), and rs6504950 (STXBP4) with breast cancer. Women in the score’s highest quintile had 2.2-fold increased risk when compared to women in the lowest quintile (95 % confidence interval: 1.67–2.88). The quadratic polygenic score term was not significant in the model (p = 0.85), suggesting that the established breast cancer loci are not associated with increased risk more than the sum of risk alleles. Modifications of menstrual and reproductive risk factors associations with breast cancer risk by polygenic score were not observed. Our results suggest that the interactions between breast cancer susceptibility loci and reproductive factors are not strong contributors to breast cancer risk.