Breast Cancer Gene Mutations Research Articles

Imaging of primary fallopian tube carcinoma

To increase awareness of primary fallopian tube carcinoma (PFTC) and its relationship to serous epithelial ovarian carcinoma (EOC) and breast cancer. To review the characteristic imaging findings of PFTC thereby enabling radiologists to not only diagnose, but aid clinicians in staging, treatment planning and surveillance for recurrence. There is increasing evidence of a relationship between PFTC and breast cancer and the breast cancer susceptibility gene mutation. Furthermore, studies in breast cancer gene mutation carriers suggest serous EOC arises from the epithelial lining of the fallopian tube. These theories indicate that the incidence of fallopian tube carcinoma is underestimated. Increased awareness is particularly important for radiologists reviewing surveillance studies in breast cancer patients. PFTC has characteristic imaging features that can aid in its detection and differentiation from other pelvic masses. Imaging is also helpful in tumor staging, identifying patients who may benefit from neoadjuvant chemotherapy and detection of recurrence following treatment. This article discusses the history, pathology, and patterns of spread of fallopian tube carcinoma, as well as reviewing and illustrating the cross-sectional imaging findings.

Role of ERRF, a Novel ER-Related Nuclear Factor, in the Growth Control of ER-Positive Human Breast Cancer Cells

Whereas estrogen-estrogen receptor α (ER) signaling plays an important role in breast cancer growth, it is also necessary for the differentiation of normal breast epithelial cells. How this functional conversion occurs, however, remains unknown. Based on a genome-wide sequencing study that identified mutations in several breast cancer genes, we examined some of the genes for mutations, expression levels, and functional effects on cell proliferation and tumorigenesis. We present the data for C1orf64 or ER-related factor (ERRF) from 31 cell lines and 367 primary breast cancer tumors. Whereas mutation of ERRF was infrequent (1 of 79 or 1.3%), its expression was up-regulated in breast cancer, and the up-regulation was more common in lower-stage tumors. In addition, increased ERRF expression was significantly associated with ER and/or progesterone receptor (PR) positivity, which was still valid in human epidermal growth factor receptor 2 (HER2)-negative tumors. In ER-positive tumors, ERRF expression was inversely correlated with HER2 status. Furthermore, higher ERRF protein expression was significantly associated with better disease-free survival and overall survival, particularly in ER- and/or PR-positive and HER2-negative tumors (luminal A subtype). Functionally, knockdown of ERRF in two ER-positive breast cancer cell lines, T-47D and MDA-MB-361, suppressed cell growth in vitro and tumorigenesis in xenograft models. These results suggest that ERRF plays a role in estrogen-ER-mediated growth of breast cancer cells and could, thus, be a potential therapeutic target.

Identification of breast cancer susceptibility genes using whole exome sequencing

Recent advances in technology have opened up the possibility of using next generation sequencing to efficiently uncover predisposing mutations in individuals with inherited cancer in an unbiased manner. We are conducting whole exome sequence analysis of germline DNA from multiple affected relatives from breast cancer families with the aim of identifying rare protein truncating and non-synonymous variants that are likely to include novel cancer predisposing mutations. Data from >70 exomes show that on average each individual only carries 30-50 protein truncating mutations and 300-400 rare non-synonymous missense variants. By considering only those variants shared by multiple affected relatives the number of candidate predisposing mutations can be dramatically reduced to just 3-5 truncating mutations and 10-20 nonsynonymous variants per family. Among the first 10 breast cancer families studied in detail, two harbour mutations in known breast cancer genes that were missed by clinical genetic testing either because the index case was a phenocopy who did not carry the mutation (BRCA2) or because the gene is not routinely tested in the context of breast cancer without additional clinical manifestations (PTEN). Among the remaining families candidate genes are currently being assessed for segregation among family members and for prevalence among an addition 800+ unexplained breast cancer families. In particular, we found truncating mutations in two genes that are involved in well-recognised DNA repair pathways but have not previously been associated with an increased risk of breast cancer. In summary, whole exome sequencing of multiple individuals from within each cancer family is proving to be an efficient strategy for rapidly identifying novel familial predisposing mutations.

The GISS Trial: a Phase II Prevention Trial of Screening Plus Goserelin, Ibandronate, versus Screening Alone in Premenopausal Women at Increased Risk of Breast Cancer

Genetic testing for inherited mutations in breast cancer genes provides valuable information for disease prevention. Today, premenopausal women with increased risk for breast cancer have only limited nonsurgical options to reduce their risk. The GISS trial, a randomized, multicenter, open-label phase II trial, assessed the feasibility of a preventive treatment with goserelin and ibandronate for premenopausal women at increased risk for breast cancer. The primary endpoints were refusal to undergo randomization and discontinuation of treatment. Safety and quality of life were also evaluated. Between the years 2001 and 2003, 31 of 322 eligible women participated in the trial; 15 received goserelin/ibandronate plus screening, 15 screening only, and 1 withdrew her consent after randomization. The treatment duration was 24 months. Here, mainly the results from the first 12 months were evaluated because of the low compliance thereafter. Hot flushes, headache, and vaginal dryness/discharge occurred more often in the goserelin arm. No difference was observed between the two arms in the agreement to randomization, compliance, or any other endpoints. Acceptance of chemoprevention with goserelin and ibandronate was low. Premenopausal women at increased risk for breast cancer should be better informed about chemoprevention through physician counseling and a more feasible study design (e.g., oral medication) should be provided. This is the first chemoprevention trial in premenopausal women at increased risk for breast cancer.

Earlier age of onset of BRCA mutation‐related cancers in subsequent generations

Women who are diagnosed with a deleterious mutation in either breast cancer (BRCA) gene have a high risk of developing breast and ovarian cancers at young ages. In this study, the authors assessed age at diagnosis in 2 generations of families with known mutations to investigate for earlier onset in subsequent generations. Of the 132 BRCA-positive women with breast cancer who participated in a high-risk protocol at The University of Texas MD Anderson Cancer Center (Gen 2), 106 women could be paired with a family member in the previous generation (Gen 1) who was diagnosed with a BRCA-related cancer (either breast cancer or ovarian cancer). Age at diagnosis, location of the mutation, and year of birth were recorded. A previously published parametric anticipation model was applied in these genetically predisposed families. The median age of cancer diagnosis was 42 years (range, 28-55 years) in Gen 2 and 48 years (range, 30-72 years) in Gen 1 (P < .001). [corrected]. In the parametric model, the estimated change in the expected age at onset for the entire cohort was 7.9 years (P < .0001). Statistically significant earlier ages at diagnosis also were observed within subgroups of BRCA1 and BRCA2 mutations, maternal inheritance, paternal inheritance, breast cancer only, and breast cancer-identified and ovarian cancer-identified families. Breast and ovarian cancers in BRCA mutation carriers appeared to be diagnosed at an earlier age in later generations. The authors concluded that patients who are younger at the onset of BRCA-related cancers should continue to be tracked to offer appropriate screening modalities at appropriate ages.

Association of death receptor 4 variant (683A&gt;C) with ovarian cancer risk in BRCA1 mutation carriers

Dysregulation of apoptosis plays an important role in carcinogenesis. Therefore, apoptosis-associated genes like the death receptor 4 (DR4, TRAIL-R1) are interesting candidates for modifying the penetrance of breast and ovarian cancer in carriers of BRCA1 and BRCA2 mutations. The DR-4 haplotype 626C-683C [626C > G, Thr209Arg (rs4871857) and 683A > C, Glu228Ala (rs17088993)] has recently been linked to an increased risk of breast cancer. To evaluate whether DR4 626C > G or DR4 683A > C modifies the risk of breast or ovarian cancer in carriers of BRCA1 and BRCA2 mutations, we undertook a national multicenter study including data of 840 carriers of breast cancer gene (BRCA) mutations. DNA samples were collected from 12 German research centers between 1996 and 2005 and were genotyped by the Taqman allelic discrimination assay. The association between genotypes and incidence of breast or ovarian cancer data was evaluated using a Cox proportional hazards regression model. We found evidence for a significant association of DR4 683A > C with a higher risk for ovarian cancer in carriers of BRCA1 mutations [n = 557, hazard ratio 1.78 (1.24-2.55), p = 0.009]. Our results thus indicate that the DR4 683A > C variant modifies the risk of ovarian cancer in carriers of BRCA1 mutations.

A functional assay for the identification of DNA double-strand break repair deficiency in heterozygous carriers of BRCA1/2 and RAD51C mutations.

561 Background: Mutations in breast cancer gene 1 and 2(BRCA1/2) account for 50% of the familial aggregation of breast and ovarian cancer. About one third of the mutations are of unknown pathogenetic relevance (unclassified variants, UCV). We recently identified RAD51C as a third high penetrance gene (Meindl et al., 2010). Like BRCA1/2, RAD51C is also involved in homologous recombination repair (HRR) in response to DNA double strand breaks. It has recently been shown that cells with HRR deficiency are sensitive to synthetic lethality mediated by PARP inhibition. Under the assumption that further high risk genes may exist which acts through the HRR pathway we aimed to develop a reliable functional test system which allows the evaluation of HRR deficiency in heterozygous carriers. Methods: We included eight carriers of a pathogenic BRCA2 mutation, two carriers of a pathogenic RAD51C mutation and nine healthy controls as well as seven BRCA2 UCV carriers. Patient and control lymphocytes were γ-irradiated in G2 phase to introduce DNA-DSB. For the assessment of HRR capacity, metaphase chromosomes were stained by multicolour fluorescence in situ hybridisation (M-FISH). Chromosomal translocations and breakages were counted per mitosis and referred to total chromosomal number. The aberration frequency of BRCA2 and RAD51C carriers versus the controls was compared. Results: Lymphocytes from BRCA2 and RAD51C pathogenic mutation carriers versus controls showed a mean aberration frequency of 2.51±0.36 (standard deviation, SD) and 2.7±0.25 (SD), respectively, versus 1.4±0.44 (SD) chromosomal aberrations per metaphase with no overlap (p-value <0.001; Student’s t-test). Seven patients carrying an UCV in BRCA2 could be allocated to either the pathogenic or the control group. Conclusions: Our test system allows the detection of HRR deficiency in heterozygous lymphocytes of BRCA2 and RAD51C gene mutation carriers and is currently evaluated in BRCA1 positive cases. The assay may enable the identification of HRR deficiency irrespective of the underlying gene defect and may also serve as a biomarker for sensitivity to PARP inhibition.

Inherited Mutations in Breast Cancer Genes—Risk and Response

Germ-line mutations in BRCA1 and BRCA2 confer a high risk of developing breast cancer. They account, however, for only 40% of strongly familial breast cancer cases. Intensive genome-wide searches for other highly-penetrant BRCA genes that, individually account for a sizeable fraction of the remaining heritability has not identified any plausible candidates. The "missing heritability" is thought to be due to cumulative effects of susceptibility alleles associated with low to moderate penetrance, in accordance with a polygenic model of inheritance. In addition, a large number of individually very rare, highly penetrant variants could account for part of the gap. Meanwhile, an understanding of the function of BRCA1 and BRCA2 in the DNA damage response pathway has lead to the identification of a number of breast cancer susceptibility genes including PALB2, CHEK2, ATM and BRIP1, all of which interact directly or indirectly with BRCA1 or BRCA2. Knowledge of how BRCA1 and BRCA2 maintain genomic integrity has also led the development of novel targeted therapies. Here we summarize the recent advances made in the understanding of the functions of these two genes, as well as the risks and responses associated with mutations in these and other breast cancer susceptibility genes.

Effectiveness of alternating mammography and magnetic resonance imaging for screening women with deleterious BRCA mutations at high risk of breast cancer

Magnetic resonance imaging (MRI) has been used to supplement screening mammography and clinical breast examination (CBE) in women who are at high risk of developing breast cancer. In this study, the authors investigated the efficacy of alternating screening mammography and breast MRI every 6 months in women who had a genetically high risk of developing breast cancer. A retrospective chart review was performed on all women who were seen in a high-risk breast cancer clinic from 1997 to 2009. Patients with breast cancer gene (BRCA) mutations who underwent alternating screening mammography and breast MRI every 6 months were included in the study. Mammography, ultrasonography, MRI, and biopsy results were reviewed. Of 73 patients who met the study criteria, 37 had BRCA1 mutations, and 36 had BRCA2 mutations. Twenty-one patients (29%) completed 1 cycle of mammography and MRI surveillance, 23 patients (31%) completed 2 cycles, 18 patients (25%) completed 3 cycles, and patients 11 (15%) completed ≥ 4 cycles. The median follow-up was 2 years (range, 1-6 years). Thirteen cancers were detected among 11 women (15%). The mean tumor size was 14 mm (range, 1-30 mm), and 2 patients had bilateral cancers. Twelve of 13 cancers were detected on an MRI but not on the screening mammography study that was obtained 6 months earlier. One cancer (a 1-mm focus of ductal carcinoma in situ) was an incidental finding in a prophylactic mastectomy specimen. One patient had ipsilateral axillary lymphadenopathy identified on ultrasonography but had no evidence of lymph node involvement after neoadjuvant chemotherapy and surgery. In women who were at genetically high risk of developing breast cancer, MRI detected cancers that were not identified on mammography 6 months earlier. Future prospective studies are needed to evaluate the benefits of this screening regimen.

Interest in Genetic Testing for Modest Changes in Breast Cancer Risk: Implications for SNP Testing

Background: Advances in genomics may eventually lead to ‘personalized genetic medicine,’ yet the clinical utility of predictive testing for modest changes in risk is unclear. We explored interest in genetic testing for genes related to modest changes in breast cancer risk in women at moderate to high risk for breast cancer. Methods: Women (n = 105) with a negative breast biopsy and ≧1 relative with breast or ovarian cancer completed telephone surveys. We measured demographic and psychosocial variables and, following presentation of hypothetical scenarios of genetic tests for lower-penetrance breast cancer gene mutations, assessed interest in willingness to pay for and comprehension of test results. We used logistic regression models with generalized estimating equations to evaluate combinations of risk level, cost and behavioral modifiers. Results: Many women (77%) reported ‘definite’ interest in genetic testing, with greater interest in tests that conveyed more risk and cost less. Behavioral modifiers of risk (taking a vitamin; diet/exercise), having a regular physician, greater perceived benefits of genetic testing, and greater cancer worry also influenced interest. Most participants (63%) did not understand relative vs. absolute risk. Women with less understanding reported more cancer worry and greater willingness to pay for testing. Conclusion: Interest in genetic testing for mutations related to modest changes in risk was high, modified by both test and psychosocial factors. Findings highlight the need for education about benefits and risks of testing for mutations that convey modest changes in risk, particularly given the current lack of clinical validity/utility and availability of direct-to-consumer genetic testing.

An amalgamated risk estimation model (REM) and assay integration into future REMs

The clinical reality of the post-genomic era is that we now face even more complex disease processes when provided with genomic information, including multifactorial genetic and genomic influences, and epigenetic and environmental factors. A useful example of the promise and perils of genomic technologies and information is breast cancer. By the mid-1990s, two genes (BRCA1 and BRCA2) had been identified, accounting for approximately 5% of affected individuals. Since then, surprisingly few genetic breast cancer risk factors have been identified to account for the remaining 95%. To efficiently and cost-effectively identify individuals at high risk, a combination of information components is required: a patient-reported personal and family medical history; clinical data (for example, a physical exam, pathology results, laboratory test results and imaging); and genetic/genomic results. Gaining comprehensive data from all of these areas provides the best risk assessment and management options for patients. Furthermore, high quality patient and clinical information is essential for the accurate and reliable interpretation of genomic results. We have clinically implemented a platform that integrates all three informational components with multiple risk estimation models (REMs) to produce an effective automated method for risk-stratifying patients. Although this platform can be and has been applied to a wide range of genetic conditions, this presentation will use breast cancer to illustrate the approach. This system consists of three primary components: a secure web-based questionnaire used by patients to enter personal and family medical history; a tablet-based system for collecting clinical and genomic information; and an analysis engine that seamlessly integrates REMs that have been developed to calculate either a woman’s risk of developing breast cancer during her lifetime (Claus, Gail II, BRCAPRO, BOADICEA and IBIS) or the probability of detecting a hereditary breast cancer gene mutation (Myriad, Penn II, BRCAPRO, BOADICEA and IBIS).This use of multiple or amalgamated REM (aREM) results offers one of the most comprehensive breast cancer risk assessments available for predicting the lifetime risk of developing breast cancer or the presence of BRCA mutations. Additional uses for aREMs include rapid analyses of existing breast cancer datasets, external validation of new REMs, and prospective outcome comparisons based on initial aREM results. Numerous biomarkers for breast cancer, in addition to BRCA1 and BRCA2 mutations, have been reported, but few molecular markers or assays have been adopted for clinical use. The addition of novel REMs that integrate a new molecular assay or classifiers can facilitate the identification of an enriched population for screening (for example, lowering the number needed to screen) or for diagnostic, prognostic or therapeutic purposes. REMs are rapidly integrating multiple genetic influences, whole genome sequencing data and epigenetic modifications, so structured comparisons of the performance of existing and emerging predictive REMs are required for safe and effective clinical application.

Electrochemical biosensor microarray functionalized by means of biomolecule friendly photolithography

Microfabrication permits the incorporation of dense electrode arrays in microsystems and small volume diagnostic devices. However, the specific functionalization of arbitrary shape electrodes with different biomolecules remains a challenging issue. In the present work, the problem of fabricating closely spaced microelectrodes (20 μm sensor diameter and 20 μm-spaced interdigitated electrodes array) that can be modified selectively in order to create multi-analyte sensor arrays is addressed by employing a biomolecule friendly photolithographic procedure for the sequential immobilization of different biomolecules onto separated electrodes of the same array. The concept was demonstrated with selective detection of oligonucleotides for breast cancer gene mutation detection, the hormone T4 detected with specific antibodies and sarcosine and glucose detected with specific enzymes immobilized in two-analyte arrays in order to assure that the method is compatible with all the types of biorecognition molecules used in biosensors. Electrochemical techniques were used in this array, because of the low cost, high sensitivity and easy miniaturisation of these transducers. Although the array was composed of only two sets of electrodes, the results demonstrate that the method proposed is generic and could be used for patterning of electrochemical multi-analyte biosensors at even higher resolution.

Acute Myelogenous Leukemia and Myelodysplasia Secondary to Breast Cancer Treatment: Case Studies and Literature Review

Background and PurposeChemotherapy and radiation therapy for breast cancer are known to increase the risk of developing a myelodysplastic syndrome (MDS) and/or acute myelogenous leukemia (AML). Alkylating agents and topoisomerase II inhibitors, fundamental to the treatment of breast cancer, are the most likely contributors to this increase in risk. Radiation therapy adds to the risk, and there is speculation that granulocyte colony-stimulating factor (G-CSF) may also predispose to leukemia. The purpose of this systemic review is to bring to the attention of family physicians the unintended consequence of leukemia secondary to aggressively treated breast cancer. MethodsThe medical records of several patients from Robert Wood Johnson University Hospital, with previously treated breast cancer admitted for therapy for AML or myelodysplasia, were reviewed. In addition, the recent literature on this topic was reviewed. ResultsCases of patients whose AML was likely secondary to their treatment for breast cancer were used to illustrate the role of chemotherapy, radiation therapy, and perhaps G-CSF in the development of leukemia. ConclusionsChemotherapy and radiation therapy administered for breast cancer predispose patients to the development of MDS or AML. We hypothesize that the breast cancer (BRCA) gene mutations might add to the risk and that primary care physicians must be aware of the long-term risks of cytotoxic therapy, including the development of MDS or AML.

BRCA1 and BRCA2 mutations in women of different ethnicities undergoing testing for hereditary breast-ovarian cancer.

In women at increased risk for breast and ovarian cancer, the identification of a mutation in breast cancer gene 1 (BRCA1) and BRCA2 has important implications for screening and prevention counseling. Uncertainty regarding the role of BRCA1 and BRCA2 testing in high-risk women from diverse ancestral backgrounds exists because of variability in prevalence estimates of deleterious (disease-associated) mutations in non-white populations. In this study, the authors examined the prevalence of BRCA1 and BRCA2 mutations in an ethnically diverse group of women who were referred for genetic testing. In this cross-sectional analysis, the prevalence of BRCA1 and BRCA2 mutations was assessed in a group of non-Ashkenazi Jewish women who underwent genetic testing. From 1996 to 2006, 46,276 women who met study criteria underwent DNA full-sequence analysis of the BRCA1 and BRCA2 genes. Deleterious mutations were identified in 12.5% of women, and recurrent deleterious mutations (prevalence >2%) were identified in all ancestral groups. Women of non-European descent were younger (mean age, 45.9 years; standard deviation [SD], 11.6 years) than European women (mean age, 50 years; SD, 11.9 years; P < .001). Women of African (15.6%; odds ratio [OR], 1.3 [95% confidence interval (95% CI), 1.1-1.5]) and Latin American (14.8%; OR, 1.2 [95% CI, 1.1-1.4]) ancestries had a significantly higher prevalence of deleterious BRCA1 and BRCA2 mutations compared with women of Western European ancestry (12.1%), primarily because of an increased prevalence of BRCA1 mutations in those 2 groups. Non-European ethnicity was associated strongly with having a variant of uncertain significance; however, reclassification decreased variant reporting (from 12.8%-->5.9%), and women of African ancestry experienced the largest decline (58%). Mutation prevalence was found to be high among women who were referred for clinical BRCA1 and BRCA2 testing, and the risk was similar across diverse ethnicities. BRCA1 and BRCA2 testing is integral to cancer risk assessment in all high-risk women.

Análisis de las mutaciones más frecuentes del gen BRCA1 (185delAG y 5382insC) en mujeres con cáncer de mama en Bucaramanga, Colombia

Breast cancer is considered a worldwide public health problem, and, in Santander Province, Colombia, it is the first leading cause of morbidity and mortality by cancer in women. All cancers are considered genetic diseases, and mutations in BRCA (BReast CAncer) genes raises the risk for breast cancer by 60%-80%. The current study searched for the two most frequent BRCA1 mutations reported in the Breast Cancer Core Information database. The presence of specific mutations (185delAG, exon 2 and 5382insC, exon 20) was determined for the BRCA1 gene in women with familial/hereditary breast cancer. The sample included 30 female patients using the oncology services in Bucaramanga, eastern Colombia; an informed consent, a questionnaire and a blood sample were obtained from each. The molecular analysis was done with PCR-Mismatch, to detect the insertion or eliminatation of a restriction site, and enzymatic digestion methods (Hinfl or Ddel). Two of the most frequent BRCA1 mutations in the international database were not found in the 30 patients studied. Additional mutation screening techniques are necessary involving the entire BRCA1 gene, are necessary in order to better characterize the molecular epidemiology of breast cancer in Bucaramanga, Santander, Colombia.

Consideration of hereditary nonpolyposis colorectal cancer in BRCA mutation‐negative familial ovarian cancers

Inherited mutations account for approximately 10% of all epithelial ovarian cancers. Breast cancer (BRCA1 and BRACA2) gene mutations are responsible for up to 85% of inherited breast and/or ovarian cancer. Another condition that has been associated with ovarian cancer is hereditary nonpolyposis colorectal cancer syndrome (HNPCC), which carries a lifetime risk of up to 13% for ovarian cancer. The objective of this study was to determine the incidence of HNPCC-related gene mutations in patients with familial ovarian cancer who previously tested negative for BRCA1 and BRCA2 gene mutations. Seventy-seven probands were identified who had familial ovarian cancer and negative BRCA gene mutation testing. Their pedigrees were analyzed for HNPCC syndrome. DNA samples underwent gene sequencing and Southern blot analysis for mutations in the 3 most common HNPCC-associated genes: mutL homolog 1 (MLH1) and mutS homolog 2 (MSH2) with reflex testing for MSH6 if tests for the first 2 genes were negative. None of the probands met Amsterdam criteria for the clinical diagnosis of HNPCC. DNA testing revealed 2 patients (2.6%) with deleterious mutations in the MSH2 gene. An additional 8 patients (10.4%) had substitutions in either the MLH1 gene or the MSH2 gene that were classified as variants of uncertain significance. If Amsterdam criteria were expanded to include ovarian cancer, then 15 of 77 patients (19.5%) would have met these expanded criteria. One deleterious mutation was noted in this group, yielding a mutation incidence of 6.7%. This percentage may be even higher if any of the identified variants of uncertain significance are confirmed to be deleterious. HNPCC should be considered when evaluating patients with suspected hereditary ovarian cancer who have had negative BRCA mutation testing.

Entertainment-Education in a Media-Saturated Environment: Examining the Impact of Single and Multiple Exposures to Breast Cancer Storylines on Two Popular Medical Dramas

In the United States, entertainment-education (E-E) initiatives in primetime television that provide public health information are at risk for diminished impact due to the media-saturated environment in which they must compete. One strategy to overcome this limitation is to use multiple primetime TV shows to reinforce similar health messages in multiple storylines. The current study explores such an approach by evaluating the impact of two separate breast cancer genetics storylines featured on two different TV programs as the result of outreach to writers and producers. These storylines aired within approximately 3 weeks of each other on the popular medical dramas, ER (NBC) and Grey's Anatomy (ABC), and included information about the BRCA1 breast cancer gene mutation and the risks it poses to women who test positive for it. The evaluation used data collected from a panel sample of 599 female survey respondents at three points in time. Results show that while the individual storylines had a modest impact on viewers' knowledge, attitudes, and behaviors related to breast cancer, combined exposure seemed to be most effective at changing outcomes. Implications of our findings for future E-E interventions and evaluations are discussed.

The American Cancer Society guidelines for breast screening with magnetic resonance imaging

The American Cancer Society (ACS) guidelines for screening with breast magnetic resonance imaging (MRI) recommend MRI for women who have a lifetime risk > or = 20% of developing breast cancer. Genetic testing for breast cancer gene (BRCA) mutations is offered to women who have a risk > or = 10% of carrying a mutation. The objectives of the current study were 1) to identify the number of women in a breast cancer screening population who had > or = 20% lifetime breast cancer risk and, thus, were candidates for screening MRI; and 2) to determine the number of women who had > or = 10% risk of BRCA mutation yet had <20% lifetime risk of breast cancer and, thus, may not have been identified as candidates for MRI screening. From 2003 to 2005, women who underwent screening mammography completed a self-administered questionnaire regarding breast cancer risk factors. For each patient, the lifetime breast cancer risk and the risk of BRCA mutation was determined by using the computerized BRCAPRO breast cancer risk-assessment model. Of 18,190 women, 78 (0.43%) had > or = 20% lifetime risk of breast cancer, all of whom had > or = 10% risk of carrying a BRCA mutation. An additional 374 women (2.06%) had <20% lifetime breast cancer risk but > or = 10% risk of mutation. Overall, there were 183 (1%) predicted mutation carriers, 27 women (0.15%) who had > or = 20% lifetime risk of breast cancer, and 62 women (0.34%) who had > or = 10% risk of mutation but <20% lifetime breast cancer risk. The ACS guidelines for breast MRI screening may systematically exclude MRI screening for many women who have a substantial risk for BRCA mutation. The current results demonstrated a need for greater awareness of breast cancer risk factors in the screening mammography population, so that high-risk women can be identified and given access to genetic testing and counseling regarding all risk-reducing interventions.

Ashkenazi Jews and Breast Cancer: The Consequences of Linking Ethnic Identity to Genetic Disease

We explored the advantages and disadvantages of using ethnic categories in genetic research. With the discovery that certain breast cancer gene mutations appeared to be more prevalent in Ashkenazi Jews, breast cancer researchers moved their focus from high-risk families to ethnicity. The concept of Ashkenazi Jews as genetically unique, a legacy of Tay-Sachs disease research and a particular reading of history, shaped this new approach even as methodological imprecision and new genetic and historical research challenged it. Our findings cast doubt on the accuracy and desirability of linking ethnic groups to genetic disease. Such linkages exaggerate genetic differences among ethnic groups and lead to unequal access to testing and therapy.

New Study Provides Comprehensive View of Breast Cancer Gene Mutations in the US Population

New Study Provides Comprehensive View of Breast Cancer Gene Mutations in the US Population