Risk For Hereditary Breast Cancer Research Articles

Participation of Korean families at high risk for hereditary breast and ovarian cancer in BRCA1/2 genetic testing.

The aim of our study was to determine the rate of participation in genetic testing, to determine the reasons for non-participation and to identify the factors affecting participation in BRCA genetic testing for high-risk patients. This study was performed through a retrospective review of 804 individuals who underwent genetic counseling for BRCA1/2 gene mutations at Seoul National University Bundang Hospital between July 2003 and September 2012. In total, 728 (90.5%) individuals underwent BRCA1/2 mutation screening after the initial genetic counseling; 88.2% of 647 probands and 100% of 157 family members were screened. In multivariate analysis, family history of breast cancer and younger age were independent variables affecting participation in genetic testing. Of the 132 people who initially declined genetic testing, 58 (43.9%) postponed the decision, 30 (22.7%) needed time to discuss the issue with family members, 22 (16.7%) did not want to know if they had a BRCA1/2 mutation, and 22 (16.7%) declined the test because of financial problems. When analyzing refusal of testing according to the time period before and after the implementation of national health insurance coverage for BRCA1/2 genetic testing, the critical reason given for refusal was different. After insurance coverage, refusal for financial reason was decreased from 61.1 to 9.6%. A family history of breast cancer and a younger age were important factors associated with participation in genetic testing. National health insurance decreased the proportion of individuals who did not participate in testing owing to a financial reason. In genetic counseling, we have to understand these issues and consider several factors that may influence an individual's decision to be tested.

Society of Gynecologic Oncology recommendations for the prevention of ovarian cancer.

Mortality from ovarian cancer may be dramatically reduced with the implementation of attainable prevention strategies. The new understanding of the cells of origin and the molecular etiology of ovarian cancer warrants a strong recommendation to the public and health care providers. This document discusses potential prevention strategies, which include 1) oral contraceptive use, 2) tubal sterilization, 3) risk-reducing salpingo-oophorectomy in women at high hereditary risk of breast and ovarian cancer, 4) genetic counseling and testing for women with ovarian cancer and other high-risk families, and 5) salpingectomy after childbearing is complete (at the time of elective pelvic surgeries, at the time of hysterectomy, and as an alternative to tubal ligation). The Society of Gynecologic Oncology has determined that recent scientific breakthroughs warrant a new summary of the progress toward the prevention of ovarian cancer. This review is intended to emphasize the importance of the fallopian tubes as a potential source of high-grade serous cancer in women with and without known genetic mutations in addition to the use of oral contraceptive pills to reduce the risk of ovarian cancer.

Next-generation sequencing for hereditary breast and gynecologic cancer risk assessment.

To summarize advances in next-generation sequencing and their application to breast and gynecologic cancer risk assessment. Next-generation sequencing panels of 6-112 cancer-associated genes are increasingly used in patient care. Studies report a 4-16% prevalence of mutations other than BRCA1/2 among patients who meet evidence-based practice guidelines for BRCA1/2 testing, with a high rate (15-88%) of uninterpretable variants of uncertain significance. Despite uncertainty about results interpretation and communication, there is early evidence of a benefit from multiple-gene sequencing panels for appropriately selected patients. Multiple-gene sequencing panels appear highly promising for the assessment of breast and gynecologic cancer risk, and they may usefully be administered in the context of cancer genetics expertise and/or clinical research protocols.

Hereditary predisposition to ovarian cancer, looking beyond BRCA1/BRCA2

ObjectiveGenetic predisposition to ovarian cancer is well documented. With the advent of next generation sequencing, hereditary panel testing provides an efficient method for evaluating multiple genes simultaneously. Therefore, we sought to investigate the contribution of 19 genes identified in the literature as increasing the risk of hereditary breast and ovarian cancer (HBOC) in a BRCA1 and BRCA2 negative population of patients with a personal history of breast and/or ovarian cancer by means of a hereditary cancer panel. MethodsSubjects were referred for multi-gene panel testing between February 2012 and March 2014. Clinical data was ascertained from requisition forms. The incidence of pathogenic mutations (including likely pathogenic), and variant of unknown significance were then calculated for each gene and/or patient cohort. ResultsIn this cohort of 911 subjects, panel testing identified 67 mutations. With 7.4% of subjects harboring a mutation on this multi-gene panel, the diagnostic yield was increased, compared to testing for BRCA1 and BRCA2 mutations alone. In the ovarian cancer probands, the most frequently mutated genes were BRIP1 (n=8; 1.72%) and MSH6 (n=6; 1.29%). In the breast cancer probands, mutations were most commonly observed in CHEK2 (n=9; 2.54%), ATM (n=3; 0.85%), and TP53 (n=3; 0.85%). ConclusionsAlthough further studies are needed to clarify the exact management of patients with a mutation in each gene, this study highlights information that can be captured with panel testing and provides support for incorporation of panel testing into clinical practice.

Frequency of Mutations in Brca1 and Brca2 Genes in Women with Breast Cancer in Córdoba, Argentina

The discovery of BRCA1 and BRCA2 genes has led to the introduction of increasingly sophisticated genetic tests to measure the risk of hereditary breast cancer, among other things. The aim of this study was to determine the prevalence of the mutation in 24 women from Cordoba with breast / ovarian cancer (BC / OC) and with at least two relatives with breast cancer. Although there are recurrent mutations, which appear repeatedly in unrelated families, with highest prevalence as in the Jewish ethnicity, this is the first study on the population of the province of Cordoba, Argentina.

Analysis of PTEN in two BRCA1 and BRCA2 wild-type familial breast cancer patients.

Sir, Our study was designed to sequence the entire exonic regions and intronic junctions of the BRCA1, BRCA2, and PTEN genes with regard to identifying the influence of PTEN mutations in two Iranian families with familial breast cancer and BRCA1/2 wild-type genes [Figure 1]. Figure 1 Pedigrees of the two families with familial breast cancer carrying new germline sequence variants in the PTEN gene: One deletion (del T IVS4-29) and one single-nucleotide substitution (IVS2+65 G>A) Mutations in particular sets of genes are associated with an increased risk of hereditary breast and ovarian cancer (HBOC). These genes are categorized into three groups according to their impact on cancer susceptibility. The first group leading to elevated breast cancer risk (40% up to 85%)[1] with mutations of high penetrance include BCRA1, BCRA2, TP53, PTEN, and STK11.[2] PTEN mutations, as a rare but high penetrance mutation, are considered following the two major known breast cancer susceptibility genes, BRCA1 and BRCA2, in HBOC development.[3] Human genomic PTEN gene locus on chromosome 10q23.3 contains 9 exons encoding a 5.5 kb messenger RNA that has a 403 amino acid open reading frame.[4] Whole gene sequencing was done for three genes in these families. The BRCA1 and BRCA2 in the proband of the families were normal, and no germline abnormality was found in these two genes that are mainly responsible for familial breast cancer. However, two new germline sequence variants were detected in the PTEN gene: One deletion (del T IVS4-29) and one single-nucleotide substitution (IVS2+65 G>A) [Figure ​[Figure2a2a and ​andb].b]. Both new changes found in the PTEN gene were analyzed by the two servers NetGene 2 and alternative splice site predictor. Del T IVS4-29 change was impositioned in NetGene 2 site, the 3’ splice site acceptor changed in the consensus sequences, but did not delete the consensus sequences. The IVS2+65 G>A variation did not cause a new change in splicing site. Figure 2 (a) Heterozygous IVS2+65 G>A of the PTEN gene. (b) Heterozygous del IVS4-29 of the PTEN gene Despite new achievements in this area, many factors leading to breast cancer predisposition are still unknown, and thus need to be identified with further investigations. All the investigations to promote strategies of early cancer diagnosis, which is critical for the survival of affected individuals, might be advantageous. As the main mechanism for activating the PTEN protein is proteasomal degradation,[5] any changes in protein structure influence the integral role of it. The specific variations that we detected may make some mute changes in the protein interactions which may prevent it from performing its task. It can be cleared by the study of protein structure in future investigations. To the best of our knowledge, the study we present here is the first analysis of the PTEN gene in BRCA1 and BRCA2 wild-type breast and/or ovarian cancer in Iranian families. Financial support and sponsorship This work was supported by grants from Iran University of Medical Sciences project number 1021. Conflicts of interest There are no conflicts of interest.

Detection of BRCA1 and BRCA2 germline mutations in Japanese population using next-generation sequencing.

Tumor suppressor genes BRCA1 and BRCA2 are the two main breast and ovarian cancer susceptibility genes, and their genetic testing has been used to evaluate the risk of hereditary breast and ovarian cancer (HBOC). While several studies have reported the prevalence of BRCA1 and BRCA2 mutations in Japanese populations, there is insufficient information about deleterious mutations compared with western countries. Moreover, because many rare variants are found in BRCA1 and BRCA2, both of which encode large proteins, it is difficult to sequence all coding regions using the Sanger method for mutation detection. In this study, therefore, we performed next-generation sequencing (NGS) analysis of the entire coding regions of BRCA1 and BRCA2 in 135 breast and/or ovarian cancer patients. Deleterious BRCA1 and BRCA2 mutations were detected in 10 patients (7.4%) by NGS analysis. Of these, one mutation in BRCA1 and two in BRCA2 had not been reported previously. Furthermore, a BRCA2 mutation found in a proband was also identified in two unaffected relatives. These data suggest the utility of screening BRCA1 and BRCA2 mutations by NGS in clinical diagnosis.

Abstract C32: Developing culturally appropriate interventions providing psychosocial and reproductive health support to young breast cancer survivors: Evaluation findings

Abstract Introduction/Objectives: Research demonstrates that after a breast cancer diagnosis, young women, especially those of racial and ethnic groups, may experience a more negative impact on their quality of life, emotional functioning, and reproductive health than older women. For women under the age of 45, African American women have the highest breast cancer incidence of any racial/ethnic group, and there is an increased risk of hereditary breast cancer among Jews who carry BRCA mutations. In conjunction with Sisters Network Inc. and Sharsheret, The Centers for Disease Control and Prevention launched a formative evaluation to understand African American and Jewish young breast cancer survivors' (YBCS) psychosocial and reproductive health needs and preferred communication channels to obtain needed health information. Methods: Sisters Network Inc. conducted four focus groups with African American YBCS. Sharsheret conducted four groups with Jewish YBCS. Thematic analysis identified major themes/patterns within and across the focus groups. Results: Fertility and sexual health were major YBCS concerns. Participants reported barriers to obtaining psychosocial and reproductive health information, including sexual taboos and lack of provider sensitivity to address these needs. Participants said that breast cancer resources are not tailored to YBCS. Participants preferred to receive breast cancer information via multiple channels, including written materials, the Internet, telephone and smartphone applications. Discussion/Implications: African American and Jewish women encounter similar barriers to obtaining psychosocial and reproductive health information. Both groups report difficulty in obtaining relevant health information and advice from their medical providers. Study findings may be used for developing of culturally-appropriate communication and interventions for YBCS that would help eliminate breast cancer health disparities in YBCS. Citation Format: Temeika L. Fairley, Natasha Buchanan, Ashani Johnson-Turbes, Leslie R. Schover, Angela R. Moore, Brandie Yancy, Dara Schleuter, Mary-Ann K. Hall, Kelly P. Hodges, Rochelle Shoretz. Developing culturally appropriate interventions providing psychosocial and reproductive health support to young breast cancer survivors: Evaluation findings. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C32. doi:10.1158/1538-7755.DISP13-C32

Do breast cancer treatment and imaging providers follow hereditary breast and ovarian cancer risk screening guidelines?

207 Background: Women with personal or family history suggestive of susceptibility to hereditary breast or ovarian cancer (HBOC) should be referred to genetic assessment (USPSTF, Ann Intern Med. 2005). Women with HBOC have a 50-85% lifetime risk of breast cancer, 30-50% of breast cancer before 50 years old,15-50% lifetime risk of ovarian cancer, and 40-60% chance of developing a second breast cancer (ASCO Cancer.net HBOC 8/2013). Our goal is to examine if this almost decade old guideline is followed in breast cancer treatment and breast cancer imaging centers in a large metropolitan area. Methods: We conducted an IRB approved web survey of all 35 breast cancer treatment sites (5 academic, 21 community, 9 public or safety net) and 58 breast imaging sites (5 academic, 27 community, 26 public or safety net) in Chicago. Results were analyzed using simple frequencies and Fisher's exact test. Results: We achieved a response rate of 91% (32/35 treatment sites, 53/58 imaging sites). We found that 56% (18/32) of treatment sites have a hereditary cancer syndrome (HBOC) screening process for newly diagnosed breast cancer patients. Most of these sites, 83% (15/18), always use genetic test results in surgical decisions, as compared to 21% (3/14) of sites that do not have an HBOC screening process, p=0.0009. Only 8% (4/53) of breast imaging sites have an HBOC screening process and provide indicated patients genetic assessment information and/or referrals. While 38% (20/53) of imaging sites conduct daily internal staff discussions of hereditary risk, only 15% of them (3/20) provide genetic assessment information to indicated patients. We found no statistically significant difference between practices of academic, community, public and safety net sites. Conclusions: Breast cancer treatment sites have partial adherence to HBOC risk screening guidelines; while breast imaging sites rarely adhere to HBOC risk assessment guidelines. Consistent HBOC risk screening protocols are needed in breast cancer treatment and breast cancer imaging sites that include providing indicated patients information about, and access to, genetic assessment.

Physician Risk Assessment Knowledge Regarding BRCA Genetics Testing

The study aim was to evaluate the association between genetics referrals, training in medical school, residency, or continuing medical education and physician knowledge of hereditary breast and ovarian cancer (HBOC). A survey of 55 questions was administered to 140 physicians evaluating knowledge and practice patterns regarding HBOC. Physicians with genetics training during residency were more likely to recognize that most instances of ovarian cancer are not hereditary (odds ratio (OR) = 3.16; 95 % confidence interval (CI) 1.32, 7.58). Physicians with continuing medical education (CME) training on genetics were more likely to identify that screening can be improved for those with a hereditary mutation (OR = 4.28; 95 % CI 1.32, 13.90). Primary care physicians who frequently referred for genetics were more likely to recognize that maternal history is not more important than paternal history (OR = 2.51; 95 % CI 1.11, 5.66), that screening can be improved for those with hereditary risk (OR = 4.06; 95 % CI 1.08, 15.22), and that females with a hereditary breast cancer risk would have different recommendations for screening than someone without this risk (OR = 4.91; 95 % CI 1.04, 23.25). Our data suggest that training and frequency of genetics referrals may be associated with knowledge of general risk assessment for HBOC.

Genomic screening of the general adult population: key concepts for assessing net benefit with systematic evidence reviews.

Genomic screening of the general adult population: key concepts for assessing net benefit with systematic evidence reviews

BRCA genetic counseling among at-risk Latinas in New York City: new beliefs shape new generation.

Despite the life-saving information that genetic counseling can provide for women at hereditary breast and/or ovarian cancer (HBOC) risk, Latinas disproportionately underuse such services. Understanding Latinas' beliefs and attitudes about BRCA genetic counseling may be the key to better health promotion within this underserved, at-risk group. We conducted 12 focus groups (N = 54) with at-risk Latina women in New York City, followed by 30 in-depth interviews among a subset of the focus group women. Both were professionally transcribed, translated where applicable and data analysis was completed by two coders trained in qualitative methods. Results revealed personal and community knowledge about BRCA genetic counseling was relatively low, although women felt largely positive about counseling. The main motivator to undergo genetic counseling was concerns about learning family members' cancer status, while the main barrier was competing demands. Generational differences were apparent, with younger women (approximately <55years) reporting that they were more interested in educating themselves about counseling and other ways to prevent cancer. Younger women were also less likely to ascribe to traditionally Latino-centered cultural beliefs which could serve as barriers (e.g. machismo, fatalismo, destino) to undergoing genetic counseling. Participants were largely enthusiastic about educational efforts to increase awareness of genetic counseling among Latinos. Revealing the beliefs and attitudes of underserved Latinas may help shape culturally appropriate educational materials and promotion programs to increase BRCA genetic counseling uptake within this underrepresented community.

Implementing a screening tool for identifying patients at risk for hereditary breast and ovarian cancer: a statewide initiative.

The Georgia Breast Cancer Genomic Health Consortium is a partnership created with funding from the Centers for Disease Control and Prevention (CDC) to the Georgia Department of Public Health to reduce cancer disparities among high-risk minority women. The project addresses young women at increased risk for hereditary breast and ovarian cancer (HBOC) syndrome through outreach efforts. The consortium provides education and collects surveillance data using the breast cancer genetics referral screening tool (B-RST) available at www.BreastCancerGeneScreen.org . The HBOC educational protocol was presented to 73 staff in 6 public health centers. Staff used the tool during the collection of medical history. Further family history assessments and testing for mutations in the BRCA1/2 genes were facilitated if appropriate. Data was collected from November 2012 through December 2013, including 2,159 screened women. The majority of patients identified as black/African American and were 18-49 years old. Also, 6.0 % (n = 130) had positive screens, and 60.9 % (n = 67) of the 110 patients who agreed to be contacted provided a detailed family history. A total of 47 patients (42.7 %) met National Comprehensive Cancer Network guidelines when family history was clarified. Fourteen (12.7 %) underwent genetic testing; 1 patient was positive for a BRCA2 mutation, and 1 patient was found to carry a variant of uncertain significance. The introduction of genomics practice within public health departments has provided access to comprehensive cancer care for uninsured individuals. The successful implementation of the B-RST into public health centers demonstrates the opportunity for integration of HBOC screening into primary care practices.

"Maybe they have found something new" participants' views on returning cohort psychosocial survey results.

Although greater attention is currently being paid to participants in research, no studies have dealt so far with the issue of returning aggregate psychosocial results to cohort participants. (i) To explore participants' views about disclosure of the aggregate results of a French national psychosocial cohort survey on the epidemiology of preventive behaviour in women from families with a hereditary breast cancer risk. (ii) To assess whether it is worth consulting participants before designing the disclosure process. A qualitative study using semi-structured face-to-face interviews and a thematic analysis based on Grounded Theory methods. Nineteen interviews were conducted with cancer-free female BRCA mutation carriers/non-carriers aged 31-79 who had participated in a cohort survey by answering self-administered questionnaires. Participants showed considerable interest in the issue of result disclosure. The preferences expressed about disclosure were rarely relevant to the topic investigated, however, as they often focused on medical knowledge about BRCA and not on the psychosocial findings obtained. This confusion may have been due to the participants' experience of the survey procedures, including its longitudinal nature, the occurrence of very few interactions with the investigators and the wide range of topics addressed in the questionnaires. Investigators should ascertain participants' expectations and preferences by consulting them before disclosing the results obtained. Although the disclosure process may not meet participants' expectations completely, consultation is the key to preventing them from having irrealistic expectations about the information they are going to receive.

Decision making after BRCA genetic testing. Down the road of transition.

The purpose of this study was to evaluate women who have completed hereditary cancer risk assessment and BRCA genetic testing to determine if they considered themselves prepared to proceed with decision making regarding cancer screening and prevention options. Levels of decisional conflict were explored, as was their preference for information delivery. The prospective, descriptive survey was conducted at a breast and clinical genetics clinic at a comprehensive cancer center in the northeastern United States. Twenty-seven female participants completed the Preparation for Decision Making scale, Decisional Conflict Scale, and a demographic questionnaire. Scores were consistent with high levels of preparation for decision making and low decisional conflict. The face-to-face approach was the preferred method for information delivery. Subgroup analysis demonstrated a difference in the measured objectives based on cancer status but not based on BRCA status. The current information delivery approach is meeting the decision-making needs of women considered to be at increased risk for hereditary breast and ovarian cancer.

Quality of life in subjects who are at high risk for hereditary breast and/or ovarian cancer.

e12501 Background: It is known that BRCA mutation carriers have a high risk of developing breast and/or ovarian cancer. Molecular-genetic investigation can effect quality of life, family life and c...

Do breast cancer treatment and imaging providers follow hereditary breast and ovarian cancer risk screening guidelines?

e17626 Background: Women with personal or family history suggestive of susceptibility to hereditary breast or ovarian cancer (HBOC) should be referred to genetic assessment (USPSTF, Ann Intern Med. 2005). Women with HBOC have a 50-85% lifetime risk of breast cancer, 30-50% of breast cancer before 50 years old,15-50% lifetime risk of ovarian cancer, and 40-60% chance of developing a second breast cancer (ASCO Cancer.net HBOC 8/2013). Our goal is to examine if this almost decade old guideline is followed in breast cancer treatment and breast cancer imaging centers in a large metropolitan area. Methods: We conducted an IRB approved web survey of all 35 breast cancer treatment sites (5 academic, 21 community, 9 public or safety net) and 58 breast imaging sites (5 academic, 27 community, 26 public or safety net) in Chicago. Results were analyzed using simple frequencies and Fisher's exact test. Results: We achieved a response rate of 91% (32/35 treatment sites, 53/58 imaging sites). We found that 56% (18/32) of treatment sites have a hereditary cancer syndrome (HBOC) screening process for newly diagnosed breast cancer patients. Most of these sites, 83% (15/18), always use genetic test results in surgical decisions, as compared to 21% (3/14) of sites that do not have an HBOC screening process, p=0.0009. Only 8% (4/53) of breast imaging sites have an HBOC screening process and provide indicated patients genetic assessment information and/or referrals. While 38% (20/53) of imaging sites conduct daily internal staff discussions of hereditary risk, only 15% of them (3/20) provide genetic assessment information to indicated patients. We found no statistically significant difference between practices of academic, community, public and safety net sites. Conclusions: Breast cancer treatment sites have partial adherence to HBOC risk screening guidelines; while breast imaging sites rarely adhere to HBOC risk assessment guidelines. Consistent HBOC risk screening protocols are needed in breast cancer treatment and breast cancer imaging sites that include providing indicated patients information about, and access to, genetic assessment.

Knowledge About Hereditary Cancer of Women with Family Histories of Breast, Colorectal, or Both Types of Cancer

Usually, the mass media do not address hereditary cancer and their risk factors, nor are these topics discussed at the community level. We used an informative guide on cancer and hereditary cancer, followed by a questionnaire on these topics to investigate the relevant knowledge among women at high risk for hereditary breast and/or colorectal cancer from a population-based cohort. The cohort was composed of 81 Brazilian women with positive family histories of breast and/or colorectal cancer. Strauss and Corbin's Grounded Theory was used for qualitative analysis. The average age of the cohort was 49.9 years old. Three participants (3.9%) were illiterate, 45 (59.2%) had attended elementary school, 14 (18.4%) had secondary school, and 14 (18.4%) held higher education degrees. A total of 47 (54.3%) volunteers were unable to fully understand the information provided in the guide because they did not know the meaning of words such as metastasis, malignant, hereditary, sporadic, or oncogenetics. Notwithstanding, the acceptance of the educational tool utilized was satisfactory, and it enhanced the volunteers' interest in a better understanding of cancer and heredity. Thereby, we concluded that the low knowledge of this important subject and the unawareness about fundamental terms required for the comprehension of this specific type of neoplasm made us believe that the use of the informative guide can provide a great value when used previously to the genetic counseling consultations. Besides, educational tools of easy understanding should be part of everyday clinical practice, from primary to specialized patient care.

Cultural Aspects of Healthy BRCA Carriers From Two Ethnocultural Groups

We explored the experiences of Ashkenazi Jewish and French Canadian women and meanings attributed to their hereditary breast and ovarian cancer (HBOC) risk. We purposively sampled 40 BRCA1 or BRCA2 (BRCA) mutation carriers and conducted theoretically driven semistructured interviews. According to content analysis, participants from these two ethnocultural groups held divergent meanings associated with being a BRCA carrier and different views pertaining to the illness experience and risk awareness. All participants identified a genetic basis; however, the French Canadian women also expressed other causes. The French Canadian women reported not knowing other carriers in their social environment, whereas the Ashkenazi Jewish women emphasized a strong sense of community contributing to their ethnic risk awareness. Based on these findings, we suggest that French Canadian women could benefit from greater awareness of the HBOC genetic risk and that health care providers should consider ethnically related and individual-based experiences and meanings during counseling.

A Race Still Unfinished

[Breast Cancer Special Issue Index][1] Few scientific endeavors captured as much public interest as the race to identify BRCA1 , a gene responsible for inherited predisposition to breast and ovarian cancers. The search culminated in a 1994 Science paper reporting the isolation of BRCA1 by positional cloning.[*][2] Isolation of the related cancer predisposition gene BRCA2 followed soon after.[†][3] Twenty years later, the BRCA genes continue to make headlines, sparking a Supreme Court decision on the legality of gene patenting and intense debates on the ethics of genetic testing. ![Figure][4] CREDIT: ANNE WESTON/CANCER RESEARCH UK/VISUALS UNLIMITED INC. In this special section of Science , expert contributors retrace the long and tortuous path leading to the mapping and identification of the BRCA1 gene; discuss the ways in which BRCA mutation status has been integrated into the clinical management of patients in high-risk families; and highlight the role of the BRCA proteins in preserving the structural and numerical integrity of chromosomes throughout the cell cycle, a function that may explain their tumor suppressor activity. Science 's News team explores many of the issues that have arisen since the discovery of the BRCA genes. Advances in molecular medicine have brought new options for treatment and prevention, driving down mortality rates in wealthy countries. But in poor countries, shut out from these advances, mortality rates remain disproportionately high. Widespread breast screening has led to early detection and a new dilemma: whether to aggressively treat noncancerous lesions that may never become invasive or whether to “watch and wait.” Since 1994, dozens more genes have been found that increase a woman's risk of hereditary breast cancer, but by how much is uncertain, confounding already complicated issues in genetic testing and counseling. Throughout this explosion of research, advocacy groups have been a powerful force in boosting funding and shaping the agenda, and they continue pushing for increasingly ambitious, some say unrealistic, goals. Clearly much more needs to be done—both more research and better ways to get existing treatments to women who need them. The discovery of the BRCA genes was transformative. More than a million women and men have been tested for BRCA1 and BRCA2 mutations in the past 20 years, and there is no doubt that the test has saved lives. But mutations in these two genes account for only 5 to 10% of breast cancer cases in the general population, and worldwide, breast cancer remains the most common and most deadly cancer in women. Is it time to start a new race? [1]: http://www.sciencemag.org/site/special/breastcancer/index.xhtml [2]: #fn-1 [3]: #fn-2 [4]: pending:yes