Breast Disease

By identifying individuals with an increased risk of breast cancer, health professionals can offer prevention strategies tailored to individual risk levels. Such strategies may include early initiation of cancer screening, more frequent screening, targeted therapeutic or behavioral interventions, or prophylactic surgery. In order to achieve clinical benefits with this approach, however, risk assessment strategies and effective prevention measures must be available. In this article we review current knowledge about cancer risk assessment for unaffected women and probability models for identifying individuals who are carriers of a mutation in BRCA1 or BRCA2, the two genes most commonly implicated in hereditary breast cancer. We review BRCA1 and BRCA2 mutations in various ethnic populations and how this information factors into risk assessment. Additionally, we summarize the current guidelines for when to make a referral to genetic services for risk assessment and evaluation.

Several genes are associated with hereditary susceptibility to breast cancer. Most notably these include BRCA1 and BRCA2; however, other less common gene mutations which confer elevated breast cancer risk are associated with Cowden syndrome, Li-Fraumeni syndrome, Peutz-Jeghers syndrome, ataxia-telangiectasia heterozygosity and hereditary diffuse gastric cancer. In this article we highlight the genetic epidemiology, gene function, genotype-phenotype correlations, cancer risks and clinicopathologic findings for the cancer susceptibility genes related to these syndromes. We also examine genes, such as CHEK2, which confer a lower penetrance for breast cancer in comparison to these highly penetrant genes.

This chapter reviews the management of women at increased risk for hereditary breast cancer. Screening strategies, emphasizing new data regarding magnetic resonance imaging (MRI), are discussed. It is recommended that women at risk for hereditary breast cancer consider annual MRI in addition to mammography and clinical breast examinations. Next, currently available data regarding chemoprevention and surgical prophylaxis for women at high risk for hereditary breast cancer are reviewed. Chemoprevention with tamoxifen reduces the risk of breast cancer by approximately 50% in a heterogeneous population of high risk women; however, the benefit in women at risk for hereditary breast cancer is less clear. In contrast, surgical prophylaxis with bilateral mastectomy reduces the risk of breast cancer by at least 90% and bilateral oophorectomy reduces the risk of breast cancer by approximately 50% among high risk women. Next, ways in which BRCA mutation-associated breast cancers differ from sporadic breast cancers are reviewed. Unique management issues pertaining to women with hereditary breast cancer are then discussed with an emphasis on surgical decision making and peri-diagnostic genetic counseling and testing. Finally, the management of women at risk for hereditary breast cancer in whom deleterious mutations are not identified is reviewed.

This article reviews the elements and process of genetic counseling for breast cancer risk, including contracting, informed consent, and psychosocial assessment and counseling. Case studies and pedigrees are utilized to illustrate current approaches to issues and challenges in the field. For example, the following topics are explored: test result interpretation, including uninformative BRCA1/2 test results; testing strategies and test selection; family concerns; patient follow-up and recontact; risk counseling in double heterozygotes; and reproductive options for mutation carriers. Concerns in specific populations such as newly diagnosed breast cancer patients, young unaffected high-risk women, and males are also reviewed. Alternative forms of and adjuncts to traditional face-to-face genetic counseling are discussed.

Over a decade has passed since the clinical availability of BRCA1/2 mutation testing for Hereditary Breast and Ovarian Cancer (HBOC). The purpose of this article is to review key areas of psychosocial and behavioral research related to genetic counseling and testing for BRCA1/2 mutations. Special attention will be given to understudied issues within each of these key areas. Where appropriate, the article will also highlight the clinical and research experiences of the authors. The first area that will be reviewed is the impact of genetic testing on psychological well-being. This will be followed by a brief discussion of a practical assessment strategy for psychosocial distress in clinical settings. Next, published data on the uptake of risk management options based on genetic testing results as well as the psychosocial impact of these behaviors will be reviewed. Thirdly, research focused on understanding the decision making at various points in the genetic counseling and testing process will also be examined. Finally, the available research on genetic counseling and testing in minority communities will be presented. By recognizing and addressing the psychosocial and behavioral issues faced by patients undergoing BRCA1/2 genetic counseling and testing, researchers and providers have the potential to maximize opportunities for prevention, early detection, and healthy coping.

Familial cancer services have been developed in many countries in response to a rapidly evolving demand for genetic counseling and testing for breast cancer risk. This article presents a synthesis of the literature on international aspects of genetic counseling and testing and discusses similarities and differences in the provision of genetic counseling and testing, taking seven countries with well established familial cancer services as a case study (Australia, Canada, France, Germany, Netherlands, UK and US). Potential international differences are discussed in terms of: provider and patient attitudes to genetic counseling and genetic testing; utilization rates of genetic testing and prophylactic surgery; and the psychological impact of genetic testing for breast cancer risk. The comparative analyses of utilization rates and the psychological impact of testing indicate a wide range of variability in uptake rates and psychological outcomes, most likely reflecting sample variability and methodological differences in measurement. International comparison studies using controlled designs would be required to ascertain whether international differences exist, and to disentangle the differential role of clinical, individual and family context factors, on the one hand, and the cultural and health system-related factors unique to particular countries, on the other.

The process of genetic testing is often deemed a family affair. Several studies have indicated that individuals undergo BRCA1/2 testing not only to learn about their own cancer risks and options for screening and prevention, but also to gather information for potentially at-risk relatives. However, many individuals are not prepared for the medical and emotional implications that accompany the genetic testing process. This can be complicated by a moral or ethical obligation to disclose result status to other family members. Several characteristics including gender, BRCA1/2 carrier status, and cultural and ethnic background may influence the communication process between the proband and his/her potentially at-risk kin. In addition, the age of family members and their degree of relatedness may affect whether or not they are told the results of their relative's genetic testing. While genetic providers have an obligation to inform individuals of the implications of BRCA1/2 test results for at-risk relatives, they must also strive to respect and maintain autonomy and confidentiality. This paper will examine the characteristics that influence the disclosure of BRCA1/2 test results to relatives. In addition, methods of post-test support and follow-up to facilitate the disclosure process for patients and their family members as well as foster positive communication, will be discussed.

Genetic breast cancer susceptibility testing presents ethical challenges for healthcare providers and their patients. The familial aspects of genetic information, recognition of DNA as a shared history and present common thread for all people and widespread misunderstandings of genetic tests all contribute to these challenges. In this article an ethical framework internationally developed as a charter for medical professionalism is used to guide approaches to ethical dilemmas of breast cancer genetic testing. Specifically, three ethical principles are explored as they relate to testing: primacy of patient, patient autonomy, and social justice. Approaching breast cancer genetic testing from this framework could help to ensure thoughtful and ethical practices in this rapidly evolving field.

The author writes a poignant “open” letter to her daughter about her experience with breast cancer, the family legacy of breast cancer, and the impact of learning that there is a BRCA1 mutation in the family.