Genetic Breast Cancer Risk Research Articles

CYP1A1, CYP1B1, GSTM1 and GSTT1 genetic variants and breast cancer risk in Mexican women.

To evaluate if variants in the genes CYP1A1 (T3801C and A4889G), CYP1B1 (G119T), GSTM1 (indel) and GSTT1 (indel) are associated with breast cancer (BC) among Mexican women. 952 incident cases with histologically confirmed BC were matched by age (± 5 years) and zone of residence with 998 healthy population controls. Genetic variants in genes CYP1A1, CYP1B1, GSTM1 and GSTT1were genotyped by allelic discrimination and multiplex PCR. In a subsample of women, 105 markers for ancestry were determined. An increased BC risk, independent of other BC risk factors, was observed among carriers of CYP1B1 G119T genotype (T/T vs. G/G: OR=1.9; 95%CI 1.4-2.5). Our results support the existence of genetic susceptibility for BC conferred by CYP1B1 G119T variant among Mexican women.

Greater need for pre-test genetic counselling, survey reveals

Misapprehension about genetic risk for breast cancer and genetic test results, in surgeons and patients, may negatively affect the choice of treatment and management, suggesting a need for greater comprehension of such information.

The Interaction between Genetic Ancestry and Breast Cancer Risk Factors among Hispanic Women: The Breast Cancer Health Disparities Study.

Background: Hispanic women have lower breast cancer incidence rates than non-Hispanic white (NHW) women. To what extent genetic versus nongenetic factors account for this difference is unknown.Methods: Using logistic regression, we evaluated the interactive influences of established risk factors and ethnicity (self-identified and identified by ancestral informative markers) on breast cancer risk among 2,326 Hispanic and 1,854 NHW postmenopausal women from the United States and Mexico in the Breast Cancer Health Disparities Study.Results: The inverse association between the percentage of Native American (NA) ancestry and breast cancer risk was only slightly attenuated after adjusting for known risk factors [lowest versus highest quartile: odds ratio (OR) =1.39, 95% confidence interval (CI) = 1.00-1.92 among U.S. Hispanics; OR = 1.92 (95% CI, 1.29-2.86) among Mexican women]. The prevalence of several risk factors, as well as the associations with certain factors and breast cancer risk, differed according to genetic admixture. For example, higher body mass index (BMI) was associated with reduced risk among women with lower NA ancestry only [BMI <25 versus >30: OR = 0.65 (95% CI, 0.44-0.98) among U.S. Hispanics; OR = 0.53 (95% CI, 0.29-0.97) among Mexicans]. The average number of risk factors among cases was inversely related to the percentage of NA ancestry.Conclusions: The lower NA ancestry groups were more likely to have the established risk factors, with the exception of BMI. Although the majority of factors were associated with risk in the expected directions among all women, BMI had an inverse association among Hispanics with lower NA ancestry.Impact: These data suggest that the established risk factors are less relevant for breast cancer development among women with more NA ancestry. Cancer Epidemiol Biomarkers Prev; 26(5); 692-701. ©2016 AACR.

Bromodomain protein 4 discriminates tissue-specific super-enhancers containing disease-specific susceptibility loci in prostate and breast cancer

BackgroundEpigenetic information can be used to identify clinically relevant genomic variants single nucleotide polymorphisms (SNPs) of functional importance in cancer development. Super-enhancers are cell-specific DNA elements, acting to determine tissue or cell identity and driving tumor progression. Although previous approaches have been tried to explain risk associated with SNPs in regulatory DNA elements, so far epigenetic readers such as bromodomain containing protein 4 (BRD4) and super-enhancers have not been used to annotate SNPs. In prostate cancer (PC), androgen receptor (AR) binding sites to chromatin have been used to inform functional annotations of SNPs.ResultsHere we establish criteria for enhancer mapping which are applicable to other diseases and traits to achieve the optimal tissue-specific enrichment of PC risk SNPs. We used stratified Q-Q plots and Fisher test to assess the differential enrichment of SNPs mapping to specific categories of enhancers. We find that BRD4 is the key discriminant of tissue-specific enhancers, showing that it is more powerful than AR binding information to capture PC specific risk loci, and can be used with similar effect in breast cancer (BC) and applied to other diseases such as schizophrenia.ConclusionsThis is the first study to evaluate the enrichment of epigenetic readers in genome-wide associations studies for SNPs within enhancers, and provides a powerful tool for enriching and prioritizing PC and BC genetic risk loci. Our study represents a proof of principle applicable to other diseases and traits that can be used to redefine molecular mechanisms of human phenotypic variation.

Content, Usability, and Utilization of Plain Language in Breast Cancer Mobile Phone Apps: A Systematic Analysis.

BackgroundBreast cancer is one of the leading contributors to preventable illness and death among women. Although mobile phone apps provide unprecedented opportunity to engage women along the cancer continuum, little is known about the availability, content, and usability of breast cancer mobile phone apps.ObjectiveThis study analyzed the content and adherence to literate design standards of all breast cancer-related apps available on the App Store and Google Play, as well as the relationship between their content, user ratings, and price.MethodsFollowing identification and downloading of all available breast cancer mobile phone apps in October 2015, 101 apps were confirmed as focusing on breast cancer. Based on prior research, we adapted and applied a content analysis scheme that was specific to breast cancer apps, including their main purpose, relevance to the cancer care continuum, and adherence to usability standards outlined by the Institute of Medicine (IOM).ResultsThe most common aim of apps was educational (73/101, 72.3%), followed by behavior change (24/101, 23.9%), fundraising (20/101, 19.8%), and advocacy (14/101, 13.9%). On the cancer continuum, primary prevention (strategies to prevent cancer cells from occurring) was mentioned in almost one-third of the apps (30/101, 29.7%). Less than half of the apps (46/101, 45.5%) presented information about mammography and/or breast clinical exam, and 53 apps (52.5%) discussed breast self-exam (which is no longer recommended). Symptoms of cancer prediagnosis, such as a lump, were discussed in almost half of the apps (48/101, 47.5%) and a similar number of apps included information about genetic risk for breast cancer (47/101, 46.5%). Information about breast cancer diagnosis was included in 42 apps (41.58%) and 43 (42.6%) apps discussed treatment options. Survivorship issues were addressed in 17 (16.8%) apps. Only one (1.0%) app discussed hospice. Adherence to usability recommendations was low. The median composite score was 3 (mean 2.60, SD 1.20) of the six recommended usability items. With eight plain language items, the median of the composite health literacy score was 5 (mean 5.06, SD 2.00). Most apps did not use easy-to-understand words (44/101, 43.6%) and few (24/101, 23.8%) defined key terms.ConclusionsCurrent breast cancer apps provide important information about breast cancer, but the most common topic covered is breast self-examination, a non-evidence-based screening strategy. Apps that focus on evidence-based strategies on the cancer continuum are needed, with a notable pressing need for apps that would address survivorship and end of life. Finally, developers of breast cancer apps should adhere to IOM standards to meet the needs of diverse populations and reduce current disparities.

Breast and ovarian cancer referrals to the ACT Genetic Service: are we meeting guidelines?

The ACT Genetic Service at The Canberra Hospital evaluates the genetic risk of individuals for inherited diseases, and provides counselling and genetic testing where appropriate. To evaluate the current referral practice for patients with a personal and/or family history of breast and/or ovarian cancer, and to assess whether these referrals are made according to eviQ cancer referral guidelines. A retrospective clinical audit of patients seen by the ACT Genetic Service for evaluation of genetic risk of breast and/or ovarian cancer between 1 January 2013 and 30 June 2015. Statistical analysis included Chi-squared and Poisson distribution tests. Of the 711 patients referred during the 30-month period, 671 were seen by the service. The number of patients seen increased steadily over the time period, as did waiting times. The majority of referrals were made by general practitioners (403/711; 57%) and oncologists (172/711; 24%). Of note, 300 of 711 (42%) of all referrals made to the service during this time period did not meet eviQ referral guidelines. Patients who met guidelines for referral were more likely both to be offered genetic testing and to have a positive result. Demand on the ACT Genetic Service increased over the time period assessed. As a significant proportion of patients did not meet eviQ cancer referral guidelines, it is worth reviewing the referral process in order to optimise utility of this limited resource.

Abstract P3-08-10: Highly accurate hereditary risk assessment tool for low-income breast cancer patients

Abstract Introduction: Genetic testing is known to improve outcomes in high-risk women by finding cancers in the earliest most treatable stage or through prophylactic measures. However, these life-saving services may not be available to low-income women due to lack of insurance or access to genetic providers. To address this need, a collaboration between the Hereditary Cancer Clinic at Vanderbilt-Ingram Cancer Center (VICC) and the Robert E. Hardy Cancer Clinic at Nashville General Hospital at Meharry Medical College (MMC) was established in 2015 to systematically screen all MMC breast cancer patients for hereditary traits and refer them for genetic counseling (1). We hypothesized that high risk women could be accurately identified using this clinic based screening tool. Methods: MMC clinic staff screened breast cancer patients using a 10-item Family Cancer Risk Assessment tool (RISK) that has been designed for use in a busy clinic environment (2). We tested the accuracy of the RISK by comparing the results to a 3-generation pedigree and the current NCCN guidelines for referral of patients to genetic services (3). The project was approved by the IRBs at each institution and study data were collected and managed using RedCap electronic data capture tools hosted at Vanderbilt University (4). Summary statistics and Chi-square for significance were performed. Results: 73 breast cancer patients completed the RISK during their clinic visits and 41 (56%) had a high-risk score of 6 or more. All 41 patients have been referred for genetic counseling, with 18 (44%) women having completed a pedigree interview over the phone. 11 of these 18 patients (61%) were African-American; 5 (27.7%) were Caucasian; and one each (5% each) were of Asian and Hispanic ancestry. 9/18 were diagnosed &amp;lt; 50 years (Mean entire group =50 yrs; range 36 -57). 5/18 (27.7%) had triple negative markers on pathology and 2/18 were ER+/PR+/Her2+, and the remainder had ER+/PR+/HER2- cancers. Among the 18 patients with full pedigrees, 17 (95%) patients met current NCCN guidelines based on pedigree analysis. The one outlier had a revised RISK score based on updated information obtained during the pedigree interview. Genetic testing was offered to 10 patients seen in VICC clinic and 1 declined testing. The other 8 patients either failed (n=4) or are awaiting an appointment (n=4). No deleterious mutations were seen in those tested. 4 VUSs (BRCA2, NBN, SMARCA4, and RAD51D) were found in 3 of the 9 tested patients. No significant differences were found in race, age or type of tumor. Conclusion: Point of care risk assessment using the Family Cancer Risk Assessment screening tool is highly accurate for identifying patients at high genetic risk for hereditary breast cancer. While the tool was completed using pen and paper, it could easily be computerized for ease of administration and calculation of risk scores. This approach benefits the busy oncologist in identifying and referring appropriate patients for genetic testing. 1. Funds awarded by GreaterGood.org. 2. Joseph G. et al. 2012 Public Health Genomics. 3. National Comprehensive Cancer Network: Genetic/High-risk Breast_Ovarian (Version 2.2016). 4. Harris et al. 2009. J Biomed Inform. Citation Format: Wiesner GL, Rao SK, Ashworth DR, Thomas KA, Lammers PE. Highly accurate hereditary risk assessment tool for low-income breast cancer patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-08-10.

Vitamin D and Breast Cancer: Latest Evidence and Future Steps.

Vitamin D (the sunshine vitamin) plays a vital role in calcium homeostasis, skeletal metabolism, and immune, cardiovascular, and reproductive systems’ functions. The worldwide prevalence of vitamin D deficiency is approximately 1 billion. Vitamin D deficiency is a serious health problem with numerous health consequences; it is associated with diabetes, rheumatic arthritis, Parkinson, Alzheimer diseases, osteomalacia, osteoporosis, and fractures in adults and cancers. Many reports showed an inverse association between serum vitamin D concentration and incidence of several cancers, including breast, colorectal, kidney, lung, and pancreatic. About 20 different cancers have incidence rates inversely related to solar UV-B doses and serum vitamin D concentration. Considering the rising incidence of breast cancer and high prevalence of vitamin D deficiency, this review aimed to reflect an association between serum vitamin D concentration and breast cancer risk, reveal the link between vitamin D receptor genetic polymorphisms and breast cancer risk, and review the relationship between vitamin D level, breast cancer risk, and prognostic factors such as tumor stage, grade, size, lymph node involvement, and hormone receptor status.

ASSOCIATION OF TRINUCLEOTIDE-REPEATCONTAINING 9 (TNRC9) SNP WITH THE RISK OF BREAST CANCER IN EGYPTIANS

Breast cancer is a heterogeneous disorder for which the underlying genetic basis remains unclear. The current study was conducted to evaluate the possible association between trinucleotide-repeatcontaining 9 (TNRC9) genetic variants and breast cancer risk in Egyptian women. Genotyping of the rs12443621 polymorphism of the TNRC9 gene by real time PCR (RT-PCR) on 100 female breast cancer patients and 80 healthy female controls was done. Breast cancer patients have significantly decreased age at menarche compared to control. Breast feeding and parity are associated with reduced breast cancer risk. The homozygous GG genotype and G allele were more frequent in the breast cancer group than in control subjects. The GG genotype frequency was associated with 2.8 times higher risk of breast cancer than AA genotype, also the G allele was associated with 1.9 times higher risk of breast cancer than A allele. The distribution of the TNRC9 rs12443621 polymorphism was significantly associated with both estrogen and progesterone receptor status. The combined AG and GG genotypes were not significantly associated with the presence of metastasis and Her2/neu status (P=0.89 and 0.49, respectively). From this study, it could be concluded that, a significant association was found between the GG genotype of TNRC9 rs12443621 and elevated breast cancer risk and signifies the TNRC9 rs12443621 G allele as being a potential risk factor for breast cancer. Further larger population-based studies are needed to confirm the prognostic value of this polymorphism in Egyptian women. Keywords: TNRC9 gene, Her2-neu, real time PCR, breast cancer.

New single nucleotide polymorphisms (SNPs) in homologous recombination repair genes detected by microarray analysis in Polish breast cancer patients.

Breast cancer is the most common cause of malignancy and mortality in women worldwide. This study aimed at localising homologous recombination repair (HR) genes and their chromosomal loci and correlating their nucleotide variants with susceptibility to breast cancer. In this study, authors analysed the association between single nucleotide polymorphisms (SNPs) in homologous recombination repair genes and the incidence of breast cancer in the population of Polish women. Blood samples from 94 breast cancer patients were analysed as test group. Individuals were recruited into the study at the Department of Oncological Surgery and Breast Diseases of the Institute of the Polish Mother's Memorial Hospital in Lodz, Poland. Healthy controls (n=500) were obtained from the Biobank Laboratory, Department of Molecular Biophysics, University of Lodz. Then, DNA of breast cancer patients was compared with one of the disease-free women. The test was supported by microarray analysis. Statistically significant correlations were identified between breast cancer and 3 not described previously SNPs of homologous recombination repair genes BRCA1 and BRCA2: rs59004709, rs4986852 and rs1799950. Further studies on larger groups are warranted to support the hypothesis of correlation between the abovementioned genetic variants and breast cancer risk.

The impact of reproductive life on breast cancer risk in women with family history or BRCA mutation.

Reproductive history and exogenous hormonal exposures are acknowledged risk factors for breast cancer in the general population. In women at increased breast cancer risk for genetic predisposition or positive family history, data regarding these risk factors are limited or conflicting, and recommendations for these categories are unclear. We evaluated the characteristics of reproductive life in 2522 women at increased genetic or familial breast cancer risk attending our Family Cancer Center. Breast cancers in BRCA mutation carriers were more likely to be hormone receptor negative, diagnosed at 35 years or before and multiple during the lifetime than tumors in women at increased familial risk, while the distribution of invasive cancers and HER2 positive tumors was similar in the different risk groups. At least one full-term pregnancy (HR 0.27; 95% CI 0.12–0.58; p = 0.001), breastfeeding either less (HR 0.24; 95% CI 0.09–0.66; p = 0.005) or more (HR 0.25; 95% IC 0.08–0.82; p = 0.022) than one year and late age at menopause (HR 0.10; 95% CI 0.01–0.82; p = 0.033) showed to be protective factors in BRCA mutation carriers, while in women at increased familial risk early age at first full-term pregnancy (HR 0.62; 95% IC 0.38–0.99; p = 0.048) and late menarche (HR 0.61; 95% CI 0.42–0.85; p = 0.004) showed to be the main protective factors. Finally, for the entire population, combined hormonal contraceptives demonstrated to do not increase breast cancer risk. The results of our study suggest that women at high familial risk and mutation carries develop tumors with different clinical-pathological characteristics and, consequently, are influenced by different protective and risk factors.

α6β4 Integrin Genetic Variations (A380T and R1281W) and Breast Cancer Risk in an Argentinian Population.

The α6β4 integrin is composed of the α6 and β4 subunits that are encoded by the ITGα6 and the ITGβ4 genes, respectively. The α6β4 main function is to intervene in lamination and epithelia integrity maintenance by cell-matrix interactions. This integrin appears to have importance in breast cancer malignancy, as well as other epithelial carcinomas. The aim of this work was to investigate the potential role of ITGα6 (A380T) and ITGβ4 (R1281W) genetic variations in breast cancer susceptibility, in a female population from the northeast region of Argentina (Misiones). We performed a case-control study of 85 breast cancer patients and 113 cancer-free controls. Genotyping was performed by RFLP-PCR. For ITGα6 (A380T) single nucleotide polymorphism, a high frequency of heterozygous genotype GA in cases compared to controls was observed, achieving values of 48% and 49%, respectively. No association between the A380T SNP and breast cancer development was found (Odds Ratio = 0.92; 95% Confidence Interval = 0.52–1.63; p = 0.884). In conclusion, we did not find evidence of an association between A380T (ITGα6) and the risk of developing breast cancer. The results represent the first report of these genetic variations in breast cancer; therefore, they are an important contribution to the literature.

Genomic Disparities in Breast Cancer Among Latinas.

Breast cancer is the most common cancer diagnosed among Latinas in the United States and the leading cause of cancer-related death among this population. Latinas tend to be diagnosed at a later stage and have worse prognostic features than their non-Hispanic white counterparts. Genetic and genomic factors may contribute to observed breast cancer health disparities in Latinas. We provide a landscape of our current understanding and the existing gaps that need to be filled across the cancer prevention and control continuum. We summarize available data on mutations in high and moderate penetrance genes for inherited risk of breast cancer and the associated literature on disparities in awareness of and uptake of genetic counseling and testing in Latina populations. We also discuss common genetic polymorphisms and risk of breast cancer in Latinas. In the treatment setting, we examine tumor genomics and pharmacogenomics in Latina patients with breast cancer. As the US population continues to diversify, extending genetic and genomic research into this underserved and understudied population is critical. By understanding the risk of breast cancer among ethnically diverse populations, we will be better positioned to make treatment advancements for earlier stages of cancer, identify more effective and ideally less toxic treatment regimens, and increase rates of survival.

Psychosocial Adjustment and Perceived Risk Among Adolescent Girls From Families With BRCA1/2 or Breast Cancer History.

To evaluate the impact of breast cancer family history and maternal BRCA1/2 mutation on the psychosocial adjustment and perceived risk in girls age 11 to 19 years old. Girls age 11 to 19 years old with one or more relatives with breast cancer or a familial BRCA1/2 mutation (breast cancer family history [BCFH] positive, n = 208; n = 69 with BRCA1/2-positive mother), peers (BCFH negative, n = 112), and their mothers completed assessments of psychosocial adjustment, breast cancer-specific distress, and perceived risk of breast cancer. General psychosocial adjustment did not differ significantly between BCFH-positive and BCFH-negative girls, either by self-report or mother report, except for higher self-esteem among BCFH-positive girls (P = .01). BCFH-positive girls had higher breast cancer-specific distress than BCFH-negative girls (P < .001), but girls from BRCA1/2-positive families did not differ from other BCFH-positive peers. BCFH-positive girls were more likely to report themselves at increased self-risk for breast cancer in adulthood than BCFH-negative peers (74% v 33%, respectively; P ≤ .001). Girls from BRCA1/2-positive families were more likely than other BCFH-positive and BCFH-negative peers to report themselves at increased risk (P < .001). In all groups, perceived risk of breast cancer was associated with older age. Higher breast cancer-specific distress among adolescent girls was associated with higher self-perceived risk of breast cancer and higher maternal breast cancer-specific distress. Adolescent girls from BRCA1/2-positive and breast cancer families have higher self-esteem and do not have poorer psychosocial adjustment than peers. However, they do experience greater breast cancer-specific distress and perceived risk of breast cancer, particularly among older girls. Understanding the impact is important to optimize responses to growing up in families at familial and genetic risk for breast cancer, particularly given the debate over the genetic testing of children for cancer susceptibility in adulthood.

Dietary choline and betaine intake, choline-metabolising genetic polymorphisms and breast cancer risk: a case-control study in China.

Choline and betaine are essential nutrients involved in one-carbon metabolism and have been hypothesised to affect breast cancer risk. Functional polymorphisms in genes encoding choline-related one-carbon metabolism enzymes, including phosphatidylethanolamine N-methyltransferase (PEMT), choline dehydrogenase (CHDH) and betaine-homocysteine methyltransferase (BHMT), have important roles in choline metabolism and may thus interact with dietary choline and betaine intake to modify breast cancer risk. This study aimed to investigate the interactive effect of polymorphisms in PEMT, BHMT and CHDH genes with choline/betaine intake on breast cancer risk among Chinese women. This hospital-based case-control study consecutively recruited 570 cases with histologically confirmed breast cancer and 576 age-matched (5-year interval) controls. Choline and betaine intakes were assessed by a validated FFQ, and genotyping was conducted for PEMT rs7946, CHDH rs9001 and BHMT rs3733890. OR and 95 % CI were estimated using unconditional logistic regression. Compared with the highest quartile of choline intake, the lowest intake quartile showed a significant increased risk of breast cancer. The SNP PEMT rs7946, CHDH rs9001 and BHMT rs3733890 had no overall association with breast cancer, but a significant risk reduction was observed among postmenopausal women with AA genotype of BHMT rs3733890 (OR 0·49; 95 % CI 0·25, 0·98). Significant interactions were observed between choline intake and SNP PEMT rs7946 (P interaction=0·029) and BHMT rs3733890 (P interaction=0·006) in relation to breast cancer risk. Our results suggest that SNP PEMT rs7946 and BHMT rs3733890 may interact with choline intake on breast cancer risk.

Largest-Ever Study on Genetic and Biological Risk of Breast Cancer in Black Women Gets NCI Funding

Largest-Ever Study on Genetic and Biological Risk of Breast Cancer in Black Women Gets NCI Funding

Understanding genetic breast cancer risk: Processing loci of the BRCA Gist Intelligent Tutoring System

The BRCA Gist Intelligent Tutoring System helps women understand and make decisions about genetic testing for breast cancer risk. BRCA Gist is guided by Fuzzy-Trace Theory, (FTT) and built using AutoTutor LITE. It responds differently to participants depending on what they say. Seven tutorial dialogues requiring explanation and argumentation are guided by three FTT concepts: forming gist explanations in one's own words, emphasizing decision-relevant information, and deliberating the consequences of decision alternatives. Participants were randomly assigned to BRCA Gist, a control, or impoverished BRCA Gist conditions removing gist explanation dialogues, argumentation dialogues, or FTT images. All BRCA Gist conditions performed significantly better than controls on knowledge, comprehension, and risk assessment. Significant differences in knowledge, comprehension, and fine-grained dialogue analyses demonstrate the efficacy of gist explanation dialogues. FTT images significantly increased knowledge. Providing more elements in arguments against testing correlated with increased knowledge and comprehension.

TCF21 genetic polymorphisms and breast cancer risk in Chinese women.

Transcription factor 21 (TCF21) functions as a tumor suppressor and is inactivated in several types of cancer. The purpose of this study is to investigate whether TCF21 genetic polymorphisms(rs2327429 T>C, rs2327430 T>C, rs2327433 A>G, rs12190287 C>G, rs7766238 G>A, rs4896011 T>A) are associated with the risk of breast cancer in Chinese women. Logistic regression analyses showed that TCF21 rs12190287 polymorphism was significantly associated with the reduced risk of breast cancer. Stratified analyses based on pathological type indicated that TCF21 rs12190287 polymorphism was only associated with the reduced risk of infiltrative ductal carcinoma. Real-time quantitative PCR analyses revealed that compared with those carrying rs12190287 CC genotype, subjects with GG genotype had higher expression levels of TCF21 mRNA in normal breast tissues. Furthermore, luciferase activity assay showed that the rs12190287 G allele weakened the binding affinity of hsa-miR-224 to TCF21 3′ UTR. These findings suggest that TCF21 rs12190287 polymorphism can regulate TCF21 expression and may serve as a potential marker for genetic susceptibility to breast cancer.

Public Health Approaches and Barriers to Educating Providers about Hereditary Breast and Ovarian Cancer Syndrome.

The Michigan Department of Health and Human Services implemented and evaluated two initiatives designed to enhance provider knowledge of patients appropriate for breast and/or ovarian cancer genetic risk assessment and hereditary breast and ovarian cancer (HBOC) syndrome testing. The first initiative targeted select providers who had diagnosed patients meeting HBOC risk criteria. Specifically, the initiative used 2008–2009 state cancer registry data to identify all providers who had diagnosed breast cancers in women ≤50 years of age, male breast cancers, and ovarian cancers in four health systems with newly established cancer genetics clinics. Using a method coined bidirectional reporting (BDR), reports highlighting how many of these cases each provider had seen were generated and mailed. Reports on 475 cancers (9.5% of the 5005 cases statewide meeting criteria) were sent to 69 providers with information about how and why to refer such patients for genetic counseling. Providers who received a report were contacted to assess whether the reports increased awareness or resulted in action (genetic counseling/referral). Based on the few responses received, despite multiple attempts to contact, and attrition rate, it is not possible to ascertain the impact of this initiative on providers. However the project resulted in the MDHHS identifying which providers see the largest proportion of at-risk patients, creating an opportunity to target those providers with HBOC education efforts. The second initiative involved creating and broadly disseminating an online, interactive case-based educational module to increase awareness and referral decisions for HBOC using high- and low-risk patient scenarios. A total of 1835 unique users accessed the module in a one year. Collectively the users viewed topic pages 2724 times and the interactive case studies 1369 times. Point of care tools (fact sheets) were viewed 1624 times and downloaded 764 times. Satisfaction among the subset of users applying for continuing medical education credit was high. The online educational module had a much broader reach than the bidirectional reporting initiative but to a self-selected audience. Combining targeted and broad-based provider education efforts may be a better way to increase HBOC awareness in the target audience, starting with those providers seeing the largest proportion of patients at risk.

Managing patients at genetic risk of breast cancer.

Hereditary syndromes that increase the risk of breast cancer are not common, but it is critical to recognize and manage them appropriately. This paper reviews the management of patients with the most common hereditary breast cancer syndromes, ie, hereditary breast and ovarian cancer syndrome, hereditary diffuse gastric cancer, Cowden syndrome (PTEN hamartoma tumor syndrome), Peutz-Jeghers syndrome, and Li-Fraumeni syndrome.