Individual Breast Cancer Risk Research Articles

Total dietary antioxidant capacity, individual antioxidant intake and breast cancer risk: the Rotterdam Study.

Some studies suggest a favorable role of antioxidants on breast cancer risk but this is still inconclusive. The aim of this study was to assess whether overall dietary antioxidant capacity, as assessed by dietary ferric reducing antioxidant potential (FRAP), and individual dietary antioxidant intake were associated with breast cancer risk. Data was used from women participating in the Rotterdam Study, a prospective cohort study among subjects aged 55 years and older (N = 3,209). FRAP scores and antioxidant intake (i.e., vitamin A, C, E, selenium, flavonoids and carotenoids) was assessed at baseline by a food frequency questionnaire. Incident cases of breast cancer were confirmed through medical reports. During a median follow-up of 17 years, 199 cases with breast cancer were identified. High dietary FRAP score was associated with a lower risk of breast cancer [hazard ratio (HR): 0.68; 95% confidence intervals (CI): 0.49, 0.96]. No overall association between individual antioxidant intake and breast cancer risk was found. However, low intake of alpha carotene and beta carotene was associated with a higher risk of breast cancer among smokers (HR: 2.48; 95% CI: 1.21, 5.12 and HR: 2.31; 95% CI: 1.12, 4.76 for alpha and beta carotene, respectively) and low intake of flavonoids was associated with breast cancer risk in women over the age of 70 (HR: 1.80; 95% CI: 1.09, 2.99). These results suggest that high overall dietary antioxidant capacity is associated with a lower risk of breast cancer. Individual effects of dietary carotenoids and dietary flavonoids may be restricted to subgroups such as smokers and elderly.

Investigación en cribado de cáncer de mama: camino hacia estrategias personalizadas y decisiones compartidas

The consolidation of population-based screening programs for breast cancer and the debate on the risk-benefit balance have coincided with the opportunity and need for research to improve the effectiveness of these programs. In Spain, in parallel to other countries with population-based programs, research on screening has evolved from the early descriptive studies of participation to longitudinal studies of adverse effects, such as false-positives and interval cancers, and studies designed to better understand the individual risk of breast cancer. These studies have been able to take advantage of the information offered by the cohort of screened women. New research methodologies have been developed to allow the evaluation of new theoretical screening strategies based on individual risk. Finally, decision-making tools are being designed to facilitate the process of informing women individually, contributing to shared decision-making.

A randomized, controlled trial to increase discussion of breast cancer in primary care.

Assessment and discussion of individual risk for breast cancer within the primary care setting are crucial to discussion of risk reduction and timely referral. We conducted a randomized controlled trial of a multiethnic, multilingual sample of women ages 40 to 74 years from two primary care practices (one academic, one safety net) to test a breast cancer risk assessment and education intervention. Patients were randomly assigned to control or intervention group. All patients completed a baseline telephone survey and risk assessment (via telephone for controls, via tablet computer in clinic waiting room before visit for intervention). Intervention (BreastCARE) patients and their physicians received an individualized risk report to discuss during the visit. One-week follow-up telephone surveys with all patients assessed patient-physician discussion of family cancer history, personal breast cancer risk, high-risk clinics, and genetic counseling/testing. A total of 655 control and 580 intervention women completed the risk assessment and follow-up interview; 25% were high-risk by family history, Gail, or Breast Cancer Surveillance Consortium risk models. BreastCARE increased discussions of family cancer history [OR, 1.54; 95% confidence interval (CI), 1.25-1.91], personal breast cancer risk (OR, 4.15; 95% CI, 3.02-5.70), high-risk clinics (OR, 3.84; 95% CI, 2.13-6.95), and genetic counseling/testing (OR, 2.22; 95% CI, 1.34-3.68). Among high-risk women, all intervention effects were stronger. An intervention combining an easy-to-use, quick risk assessment tool with patient-centered risk reports at the point of care can successfully promote discussion of breast cancer risk reduction between patients and primary care physicians, particularly for high-risk women. Next steps include scaling and dissemination of BreastCARE with integration into electronic medical record systems.

PREDICTION OF BREAST CANCER POSSIBILITY IN THE GENERAL HEALTH NETWORK

Aim of this study is to formulate an algorithm based on neural network modelling to calculate the index of individual risk of breast cancer (BC). We examined 1440 women. All subjects aged 18 to 85 years. To achieve the objective used clinical, laboratory and instrumental methods (mammography, ultrasonography). Questionnaire method, methods for constructing artificial neural network models and logistic regression models, as well as the program «oncologist» are based on a neural network. 12 women of 360 clinically healthy women surveyed were assigned to high-risk group. The majority were women 41-50 age group - (75 ± 0,1%). Women aged 51-60 totalled 16,7 ± 0,1%, in 31-40 years - 8,3 ± 0,1%. In the «medium risk» assigned 95 women - 26,4 ± 0,1%, in the « low risk « - 253 women 70,3 ± 0,1%. Statistically significant differences (p < 0,001). Belonging to high-risk groups increases the reliability of the pathological process in 2.2 (CI 1,4-3,5 ) times (p < 0,001). In women at high and medium risk of developing breast cancer as a result of a comprehensive survey found suspected breast cancer one woman (by histological examination - fibroadenoma), fibro-cystosis disease (FCD) in 18 women with one woman - fibroadenoma of the breast. In the low-risk group for breast cancer FCD was detected in 4 women, nodules were not identified. Statistically significant (p < 0,001) risk factors were set up for each age group in the Bukovynskoy region, which make up the largest proportion. An automated system (based on a neural network, which allows you to create « high-risk « of breast cancer and precancerous diseases. Sensitivity of predictive models - 79,8%, specificity - 79,0% with 86,3% diagnostic accuracy.

Genetic variation in the major mitotic checkpoint genes and risk of breast cancer: a multigenic study on cancer susceptibility

The mitotic checkpoint system is a mechanism essential for maintaining genomic stability and defects which have been linked to cancer development. We conducted this hospital-based case-control study to investigate whether genetic variants in three major spindle checkpoint genes (BUB3, MAD2L1, and BUB1) had any bearing on an individual risk of breast cancer (BC). A total of 462 incident BC patients and 529 cancer-free controls were enrolled in this study. Results showed that neither variants in BUB3 nor variants in MAD2L1 caused any significant effect on the risk of BC. However, the variant rs12623473 in BUB1 was significantly associated with increased BC risk with the odds ratio (OR) of 1.30 (95 % confidence interval (CI) 1.03-1.64) under the allelic model. The estimated population attributable risk of one copy of the risk allele for developing BC was 10.3 %. The bioinformatics analysis suggested that this variant may regulate the transcriptional ability of BUB1.

Tools of the Trade: Individualized Breast Cancer Risk Assessment

Tools of the Trade: Individualized Breast Cancer Risk Assessment

Social, ethical and legal considerations raised by the discovery and patenting of the BRCA1 and BRCA2 genes

The discovery of the BRCA1 gene had an immediate and profound impact on medical practice by providing a means to assess and manage breast and ovarian cancer risk in individuals and their families carrying a mutation in the gene. The patenting of BRCA1 and then BRCA2 (another cancer-predisposing gene) by Myriad Genetics Inc. raised controversial ethical and legal issues relating to access and research, and its enforcement caused growing discontent. In the USA, the validity of the patents on the isolated BRCA1 and BRCA2 genes was challenged in court. After a four-year legal battle, the US Supreme Court invalidated both patents. This commentary reviews the discovery of these cancer-predisposing genes from the perspective of one of the co-discoverers of BRCA1. It also discusses the socio-ethical impact of the patenting of BRCA1 and BRCA2 and the legal implications of the US Supreme Court's decision.

Modification of breast cancer risk according to age and menopausal status: a combined analysis of five population-based case–control studies

While several risk factors for breast cancer have been identified, studies have not consistently shown whether these factors operate more strongly at certain ages or for just pre- or postmenopausal women. We evaluated whether risk factors for breast cancer differ according to age or menopausal status. Data from five population-based case-control studies conducted during 1988-2008 were combined and analyzed. Cases (N = 23,959) and population controls (N = 28,304) completed telephone interviews. Logistic regression was used to estimate adjusted odds ratios and 95 % confidence intervals and tests for interaction by age and menopausal status. Odds ratios for first-degree family history of breast cancer were strongest for younger women-reaching twofold elevations-but were still statistically significantly elevated by 58-69 % among older women. Obesity was inversely associated with breast cancer among younger women and positively associated with risk for older women (interaction P < 0.0001). Recent alcohol intake was more strongly related to breast cancer risk among older women, although consumption of 3 or more drinks/day among younger women also was associated with elevated odd ratios (P < 0.0001). Associations with benign breast disease and most reproductive/menstrual factors did not vary by age. Repeating analysis stratifying by menopausal status produced similar results. With few exceptions, menstrual and lifestyle factors are associated with breast cancer risk regardless of age or menopausal status. Variation in the association of family history, obesity, and alcohol use with breast cancer risk by age and menopausal status may need to be considered when determining individual risk for breast cancer.

8LBA Assessing individual breast cancer risk within the UK National Health Service Breast Screening Programme: First prospective results from PROCAS

8LBA Assessing individual breast cancer risk within the UK National Health Service Breast Screening Programme: First prospective results from PROCAS

Zukunft mammographiebasierter Bildgebung

Mammography is the central diagnostic method for clinical diagnostics of breast cancer and the breast cancer screening program. In the clinical routine complementary methods, such as ultrasound, tomosynthesis and optional magnetic resonance imaging (MRI) are already combined for the diagnostic procedure. Future developments will utilize investigative procedures either as a hybrid (combination of several different imaging modalities in one instrument) or as a fusion method (the technical fusion of two or more of these methods) to implement fusion imaging into diagnostic algorithms. For screening there are reasonable hypotheses to aim for studies that individualize the diagnostic process within the screening procedure. Individual breast cancer risk prediction and individualized knowledge about sensitivity and specificity for certain diagnostic methods could be tested. The clinical implementation of these algorithms is not yet in sight.

Abstract P2-14-05: Sporadic breast cancer risk assessment in women without family history and biopsy using the OncoVue® polyfactorial model

Abstract Background: The majority of breast cancer cases are considered to be sporadic and occur in women without a strong family history. Accurate estimation of a woman's risk of developing breast cancer is essential for guiding decisions regarding surveillance and prevention. The Breast Cancer Risk Assessment Tool (BCRAT) uses only clinical factors and has been shown to be of marginal value for individual risk counseling. Even though the BCRAT risks for women without a biopsy and no first degree relative with breast cancer are low, a significant fraction of cases occur in these women. OncoVue® is a logistic regression model developed from individual genetic and personal factor data from a large case-control study. In three independent validation populations, including a blinded validation, OncoVue has been shown to significantly outperform BCRAT. Here we compare OncoVue to the BCRAT in stratifying risk in women without a first degree relative with breast cancer that have never had a breast biopsy. Materials and Methods: Absolute risks for Caucasian participants ranging in age from 35 to 89 were analyzed for a case-control study conducted in six distinct geographic regions of the United States. This analysis focused on participants that had never had a biopsy and reported no first degree relatives with breast cancer (cases prior to diagnosis/controls at time of enrollment). DNAs from a total of 2729 women (842 cases and 1887 controls) were genotyped for 22 SNP variants and genotype information was combined with clinical risk information to calculate 5-year and lifetime risks. Clinical factor information alone was used to calculate BCRAT risk scores for comparison to OncoVue. Results: The 5-year risks for OncoVue ranged from 0.10 to 5.0% (50-fold) compared to 0.20 to 3.0% (15-fold) for BCRAT risks. OncoVue lifetime risks ranged from 2.4 to 25.0% (11-fold) compared to 4 to 16% (4-fold) for BCRAT risks. The OncoVue model 5-year risk placed 11% of this sub-population of controls at ≥ 2.0% risk compared to the BCRAT which placed only 3.5% at this risk. The BCRAT did not place anyone at a lifetime risk over 16% while OncoVue placed 10% of this sub-population of controls above 16%. The Odds Ratio (OR) was determined at increasing model risk output levels. Over comparable ranges, OncoVue 5-year risks exhibited statistically significant ORs while BCRAT ORs did not reach significance. OncoVue associations for lifetime risk reach high levels. For example, an OR of 5.0 (p = 0.03) was observed at a risk level ≥ 23%. Conclusion: The OncoVue model stratifies risk over a much wider range than the BCRAT in this group of women at low risk by traditional methods. In the 5-year risk frame OncoVue exhibited improved performance in estimating individual risk compared to the BCRAT. Due to the lack of any elevated lifetime risks generated by the BCRAT, a direct comparison of lifetime risks for OncoVue to the BCRAT was not possible. The OncoVue model which uses both genetics and clinical factors significantly improves individualized breast cancer risk estimation. These results demonstrate the importance of the genetic component of the OncoVue model in accurately estimating individual risk of sporadic breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-14-05.

Increased Rate of Phenocopies in All Age Groups in BRCA1/BRCA2 Mutation Kindred, but Increased Prospective Breast Cancer Risk Is Confined to BRCA2 Mutation Carriers

To establish, if among unaffected noncarrier relatives in a family with an established BRCA1/2 mutation, there is an increased risk of breast cancer. We identified 49 women with breast cancer who were first-degree relatives of a pathogenic mutation carrier among 807 BRCA1/2 families but who tested negative for the specific mutation. A prospective analysis of breast cancer from date of family ascertainment was performed for first-degree relatives of proven BRCA1/2 mutation carriers and compared with population-expected incidence rates. Women who prospectively test negative for BRCA1/2 mutations showed excess risk of breast cancer to be confined to BRCA2 noncarriers with an observed:expected (O/E) ratio of 4.57 [95% confidence interval (CI) 2.50-7.67; P < 0.0001; O/E in BRCA1 noncarriers, 1.77]; this dropped to 2.01 for BRCA2 [relative risk (RR), 1.99; 95% CI, 0.54-5.10] from date of predictive test. Genotyping of 18 breast cancer susceptibility single-nucleotide polymorphisms (SNP) defined an RR of 1.31 for BRCA2 breast cancer phenocopies with a breast cancer diagnosis at age less than 60 years. Noncarriers remain at risk in the prospective follow-up of women who tested negative for BRCA1/2. Women testing negative in BRCA2 families may have increased risk of breast cancer compared with population levels, particularly with strong breast cancer history in close relatives. Any increased risk in BRCA1 families is likely to be insufficient to recommend additional interventions. Our work can help with counseling women from BRCA1/2 families who have tested negative, and could impact on how individual breast cancer risk is related back to these women.

An assessment of existing models for individualized breast cancer risk estimation in a screening program in Spain

BackgroundThe aim of this study was to evaluate the calibration and discriminatory power of three predictive models of breast cancer risk.MethodsWe included 13,760 women who were first-time participants in the Sabadell-Cerdanyola Breast Cancer Screening Program, in Catalonia, Spain. Projections of risk were obtained at three and five years for invasive cancer using the Gail, Chen and Barlow models. Incidence and mortality data were obtained from the Catalan registries. The calibration and discrimination of the models were assessed using the Hosmer-Lemeshow C statistic, the area under the receiver operating characteristic curve (AUC) and the Harrell’s C statistic.ResultsThe Gail and Chen models showed good calibration while the Barlow model overestimated the number of cases: the ratio between estimated and observed values at 5 years ranged from 0.86 to 1.55 for the first two models and from 1.82 to 3.44 for the Barlow model. The 5-year projection for the Chen and Barlow models had the highest discrimination, with an AUC around 0.58. The Harrell’s C statistic showed very similar values in the 5-year projection for each of the models. Although they passed the calibration test, the Gail and Chen models overestimated the number of cases in some breast density categories.ConclusionsThese models cannot be used as a measure of individual risk in early detection programs to customize screening strategies. The inclusion of longitudinal measures of breast density or other risk factors in joint models of survival and longitudinal data may be a step towards personalized early detection of BC.

Breast cancer risk assessment in 8,824 women attending a family history evaluation and screening programme

Accurate individualized breast cancer risk assessment is essential to provide risk-benefit analysis prior to initiating interventions designed to lower breast cancer risk and start surveillance. We have previously shown that a manual adaptation of Claus tables was as accurate as the Tyrer-Cuzick model and more accurate at predicting breast cancer than the Gail, Claus model and Ford models. Here we reassess the manual model with longer follow up and higher numbers of cancers. Calibration of the manual model was assessed using data from 8,824 women attending the family history evaluation and screening programme in Manchester UK, with a mean follow up of 9.71 years. After exclusion of 40 prevalent cancers, 406 incident breast cancers occurred, and 385.1 were predicted (O/E = 1.05, 95 % CI 0.95-1.16) using the manual model. Predictions were close to that of observed cancers in all risk categories and in all age groups, including women in their forties (O/E = 0.99, 95 % CI 0.83-1.16). Manual risk prediction with use of adjusted Claus tables and curves with modest adjustment for hormonal and reproductive factors was a well-calibrated approach to breast cancer risk estimation in a UK family history clinic.

Abstract 2272: Comparison of metformin, pheformin and buformin in mammary carcinogenesis in non-obese, non-diabetic rats.

Abstract Emerging evidence from studies of human pharmacoepidemiology indicate that metformin, an antidiabetic drug, is associated with reduced breast cancer risk in diabetic individuals. Data from preclinical mammary carcinogenesis studies in the rat indicate that metformin also has protective activity against chemically-induced mammary cancer in non diabetic rats, but the dose required for inhibition is above that used clinically for the treatment of diabetes. Human breast cancer cell growth also is inhibited by metformin, but at concentrations far in excess of anti-diabetic plasma concentrations of the drug. It is likely that pharmacokinetic/pharmacodyanmic factors contribute to this blunted sensitivity, possibly due to carcinogenesis-associated down regulation of organic cationic transporters (OCT) required for cellular uptake of metformin. Since some biguanides such as phenformin and buformin are not dependent on OCT for cellular accumulation, their effects against mammary carcinogenesis were evaluated in comparison to metformin as a proof-in-concept study that could set the stage for development of second generation biguanides. The hypothesis evaluated was that inhibition of mammary carcinogenesis by phenformin and buformin would be superior to metformin. Female Sprague Dawley rats (n=30/group) were injected with 1-methyl-1-nitrosourea (50 mg/kg) at 21 days of age and 7 days thereafter randomized to metformin, phenformin or buformin dietary groups and fed respective biguanides (10 mmol/kg) diets for 6 weeks. Both phenformin and buformin significantly reduced the number of mammary adenocarcinoma per rat (3.6, 1.6, and 0.7 cancers/rat for metformin, phenformin and buformin respectively) and tumor burden (1.61, 0.63, and 0.12 g/rat for metformin, phenformin and buformin respectively) and elongated cancer latency compared to metformin (40, 45, and 48 days post carcinogen for metformin, phenformin and buformin respectively) (p&amp;lt;0.05). Mammary cancer incidence was also lower in animals fed phenformin (77%) or buformin (43%) diet vs metformin (93%), but the difference was only significant between metformin and buformin (p&amp;lt;0.001). Cell culture experiments confirmed the carcinogenesis data. The comparative effects of these biguanides on the LKB1/AMPK axis will be reported. The associated mechanisms of cell growth inhibiton are under investigation. Supported by PHS grant CA52626 from the National Cancer Institute. Citation Format: Zongjian Zhu, Weiqin Jiang, John N. McGinley, Henry J. Thompson. Comparison of metformin, pheformin and buformin in mammary carcinogenesis in non-obese, non-diabetic rats. [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 2272. doi:10.1158/1538-7445.AM2013-2272

Abstract 3646: Promoter methylation in epithelial cells isolated from breast milk of women from Istanbul, Turkey.

Abstract Current models of assessing breast cancer risk do not adequately predict whether an individual woman will develop breast cancer. Assessment of healthy tissue for epigenetic changes that result in silencing of tumor suppressor genes may provide a more accurate assessment of individual breast cancer risk. Breast milk is an underutilized source of epithelial cells from non-symptomatic women that can be used for risk assessment. In the present pilot study, we examined promoter methylation of three tumor suppressor genes in epithelial cells isolated from breast milk of Turkish women. Forty-three women living in Istanbul, Turkey were recruited to complete a health and reproductive history questionnaire and to donate a single milk sample. Women ranged in age from 19 to 43 years old, had an average of 2 children (range: 1-5), a mean age at first birth of 25 years (range: 16-36), and a mean BMI of 26 (range 19.3-33.6). Nine percent reported smoking and thirty two percent reported exposure to second-hand smoke. Three of the 43 women had a family history of breast cancer, while four women reported having a family history of ovarian cancer. Each woman donated a single breast milk sample, with a mean volume of 17 ml (S.D. 11.6 ml, range: 2-49 ml), which was processed within 12 hours of donation. Epithelial cells were isolated from the milk via immunomagnetic beads. The breast milk samples yielded an average of 320,000 epithelial cells (S.D. 480,000, range: 10,000-2,600,000), from which DNA was extracted. Utilizing the extracted epithelial DNA, promoter methylation of three tumor suppressor genes; Rass association domain family 1(RASSF1), secreted frizzle related protein 1(SFRP1), and glutathione-S-transferase class pi 1 (GSTP1), was determined by pyrosequencing. For RASSF1 the average promoter methylation was 6.3% (n= 33); there were two outliers whose average methylation was 54.48%. For SFRP1 the average promoter methylation was 5.7 % (n= 17) with one outlier at 53.4% methylation. For GSTP1, the mean methylation was 4.4% (n= 29), with two outliers whose average methylation was 16.9%. Methylation scores were not correlated with any of the demographic factors, such as second hand smoke exposure, age or BMI. As expected of non-symptomatic breast tissue, promoter methylation scores were in general low; however, outlier scores suggest that promoter methylation may be useful in assessing risk. Long-term follow-up is required to evaluate the predictive value of promoter methylation in tumor suppressor genes. Citation Format: Eva P. Browne, Elizabeth C. Punska, Signem E. Dinc, Ayca Vitrinel, Gulay C. Erdag, Douglas L. Anderton, Kathleen F. Arcaro, Bayram Yilmaz. Promoter methylation in epithelial cells isolated from breast milk of women from Istanbul, Turkey. [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 3646. doi:10.1158/1538-7445.AM2013-3646

Pure flat epithelial atypia: Is there a place for routine surgery?

To determine whether it is appropriate to routinely undertake surgery if flat epithelial atypia (FEA) or pure flat epithelial atypia (pFEA) is found on large-core biopsy. Between 2005 and 2010, 1678 large-core biopsy procedures were carried out, which led to 136 FEA sites being identified, 63 of which across 59 patients were pFEA (four patients had two sites of pFEA each). Forty-eight patients underwent further surgical excision, equating to 52 excised sites of pFEA. Of the 52 operated sites, there were 20 benign lesions (38%), 26 borderline lesions (56%), and three ductal carcinomas in situ (6%). The rate of histologic underestimation was put at 3.8%. Of the three cases that were underestimated, one was discarded because the definitive histology was not representative of the site from which microcalcifications had initially been taken. The other two cases that were underestimated were found in patients with an increased individual risk of breast cancer. In patients with no personal or first-degree family history of breast cancer, after complete or subtotal excision under radiology of the radiological lesion, and while excluding images fitting BI-RADS 5, annual monitoring may be offered as an alternative to surgical excision in view of the absence of underestimation found in our study.

Reader Variability in Breast Density Estimation from Full-Field Digital Mammograms: The Effect of Image Postprocessing on Relative and Absolute Measures

Mammographic breast density, a strong risk factor for breast cancer, may be measured as either a relative percentage of dense (ie, radiopaque) breast tissue or as an absolute area from either raw (ie, "for processing") or vendor postprocessed (ie, "for presentation") digital mammograms. Given the increasing interest in the incorporation of mammographic density in breast cancer risk assessment, the purpose of this study is to determine the inherent reader variability in breast density assessment from raw and vendor-processed digital mammograms, because inconsistent estimates could to lead to misclassification of an individual woman's risk for breast cancer. Bilateral, mediolateral-oblique view, raw, and processed digital mammograms of 81 women were retrospectively collected for this study (N = 324 images). Mammographic percent density and absolute dense tissue area estimates for each image were obtained from two radiologists using a validated, interactive software tool. The variability of interreader agreement was not found to be affected by the image presentation style (ie, raw or processed, F-test: P > .5). Interreader estimates of relative and absolute breast density are strongly correlated (Pearson r > 0.84, P < .001) but systematically different (t-test, P < .001) between the two readers. Our results show that mammographic density may be assessed with equal reliability from either raw or vendor postprocessed images. Furthermore, our results suggest that the primary source of density variability comes from the subjectivity of the individual reader in assessing the absolute amount of dense tissue present in the breast, indicating the need to use standardized tools to mitigate this effect.

TCF7L2 rs12255372 (G &gt; T) Polymorphism Contributes to Breast Carcinogenesis: Evidence from a Meta-Analysis

Studies on the association between the TCF7L2 rs12255372 polymorphism and breast cancer risk have reported conflicting results. To characterize the relationship between this polymorphism and breast cancer risk, we conducted a comprehensive literature search for relevant studies and performed a meta-analysis. A total of four studies including 5280 cases and 6026 controls were eligible for our analysis. Overall, we did find that this polymorphism correlates with breast cancer risk [TT versus GG: odds ratio (OR)=1.19, 95% confidence interval (CI)=1.02-1.40; GT versus GG: OR=1.10, 95% CI=1.01-1.19; T versus G: OR=1.12, 95% CI=1.05-1.19]. Furthermore, in the subgroup analysis by ethnicity, we did also find that this polymorphism associated with an increased breast cancer risk in white individuals (T versus G: OR=1.11, 95% CI=1.04-1.18). In summary, this meta-analysis suggests that the rs12255372 T allele is a low-penetrant risk factor for breast carcinogenesis. In the future, larger-scale and more well-designed studies based on homogeneous breast cancer patients are needed to validate our findings, especially in Asians.

Abstract P4-13-05: The gap between perceptions of risk and actual risk for breast cancer.

Abstract Background: Estimating a woman's individual risk for breast cancer is essential for tailoring appropriate screening and risk reduction strategies. Prior research suggests that women often misperceive their risk as either higher or lower than it actually is. As a result, average risk women who perceive their risk to be high may experience unnecessary anxiety. In contrast, high risk women who perceive their risk to be average/low may not utilize needed screening or available risk reduction options. The overall aim of this study is to compare perception of breast cancer risk to actual risk among a sample of multi-ethnic women with a range of breast cancer risk. Methods: As part of BREASTCARE, a randomized controlled trial designed to evaluate a PC-tablet based intervention providing multi-ethnic women and their primary care physicians with tailored information about breast cancer risk, we collected baseline information regarding perception of risk. Women visiting general internal medicine primary care clinics at two sites (one academic practice and one safety net practice) during the study period, between the ages of 40 and 74, who spoke English, Spanish or Chinese, and had no personal history of breast cancer were eligible to participate. Participants were asked how concerned they were about getting breast cancer: very concerned, somewhat concerned, a little concerned, or not at all concerned. They were also asked what they believed their chances of getting breast cancer were compared to other women their age: higher, the same, or lower. We classified women as high risk if they had a positive family history based on the Referral Screening Tool (Bellcross, et al. 2009), or were in the top 5% estimated 5-year risk for their age group based on either the Gail Model (Gail et al. 1999) or the Breast Cancer Surveillance Consortium Model when breast density data was available (Tice et al. 2008). We then compared women's perception of breast cancer risk with their actual risk. Results: To date, data has been obtained for 913 participants. One third of the women were white, 23% Black, 23% Latina and 17% Asian. Twenty percent (N = 182) of the women were classified as high risk. Among average risk women (N = 727) 48% were very or somewhat concerned about getting breast cancer. In contrast, 35% of high risk women were a little or not at all concerned. When asked how their chances of getting breast cancer compared to other women their age, 20% of average risk women thought their risk was higher than other women their age, while 71% of those at high risk indicated that they had the same or lower risk than other women their age. Conclusions: Our results suggest that both average and high risk women have an incorrect perception of their personal breast cancer risk compared to their actual risk. Interventions that address this misunderstanding can help those at high risk to initiate appropriate risk reduction practices and those at average risk to reduce unnecessary anxiety. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-13-05.