Hereditary Breast Cancer PDF

Preface

The existence of hereditary breast cancer has been recognized for centuries. Hereditary breast cancer was first described in detail in 1866 by the French surgeon Paul Broca (1), who characterized the pattern of breast and other cancers in members of his wife's family. This early description of a hereditary syndrome involving breast cancer was refined in the subsequent 100 years to firmly establish that hereditary breast cancer occurs in a small but significant percentage of the population, that some discrete syndromes involving breast cancer exist, and that these syndromes are explained by mutations in single genes. Within the past three decades, the underlying genetic causes of hereditary breast cancer have been identified and characterized. These genes include TP53 (in Li-Fraumeni Syndrome), PTEN (in Cowden Syndrome), BRCA1 and BRCA2 (in hereditary breast/ ovarian cancer syndrome), LKB1 (in Peutz-Jeghers Syndrome), and others.

Research regarding hereditary breast cancer is now sufficiently developed to provide a strong understanding of the basic biology and epidemiology underlying hereditary breast cancer, and to allow translation of this knowledge into clinical practice. Building on the tremendous recent growth in our knowledge and application of genetic information in understanding and managing hereditary breast cancer, we have designed this volume to provide an overview of our accumulated knowledge of hereditary breast cancer, and as a guide to the current state of clinical practice. While a number of specialized referral centers exist, there has also been a growing interest in the use of genetic risk assessment, testing, and counseling for breast cancer in the wider medical community, including primary care physicians, gynecologists, oncologic surgeons, radiation oncologists, and medical oncologists. Thus, there is a critical need to better understand the epidemiology of hereditary breast cancer, apply cancer risk assessment models, and implement cancer prevention and screening options for individuals with hereditary breast cancer. A major goal of this text is to disseminate information in a comprehensive way to both specialist researchers and clinicians as well as the wider community of individuals with interests in hereditary breast cancer.

To accomplish this goal, we present a volume organized in five sections. In the first section, we provide an overview of genetic epidemiology, risk assessment models, and ethical considerations for genetic testing in hereditary breast cancer. In the second section, we present a comprehensive overview of hereditary breast cancer syndromes with known etiologies, including those associated with BRCA1 or BRCA2 mutations, Cowden Syndrome, Li-Fraumeni Syndrome, other rare syndromes involving breast cancer, and those that may be associated with low-penetrance genetic variants. In the third section, we present more detailed information about BRCA1 and BRCA2, which comprise the most common explanations for hereditary breast cancer. This section includes discussion of the biology of BRCA1- and BRCA2-associated breast cancer, genetic testing and counseling issues, molecular diagnosis, modifiers of risk, issues for underserved populations, and psychological impact of genetic testing. In the final two sections, we present a comprehensive discussion of the cancer screening, prevention, and treatment options for BRCA1- and BRCA2-associated breast and ovarian cancers.

We believe this volume provides a timely reference for the current state of knowledge regarding hereditary breast cancer and the clinical application of genetic risk assessment, counseling, testing, and management that will be of value to a wide range of clinicians and researchers.

We would like to acknowledge the families who have generously contributed their time and information to the generation of the research that is summarized in this volume.

Finally, we would like to express our appreciation to our families for their support, encouragement and patience: Claudine Isaacs' husband Steve Riskin and sons Jeffrey and Timmy; and Tim Rebbeck's wife Jill Stopfer and daughters Alanna and Sophie.