Hereditary Gynecologic Cancer: Risk, Prevention and Management PDF

I was an obstetrics-gynecology resident when the news broke in 1993 that BRCA1 had been cloned. While the name itself (BR: breast, CA: cancer gene) implied its association with hereditary breast cancers, those of us who cared for women with ovarian cancer understood that for many of these families, the ovarian cancer diagnosis was equally as devastating. Over the last 15 years, there have been large leaps in defining the specific cancer risks associated with BRCA1 and BRCA2, in outlining specific management options for risk reduction, and in understanding the psychosocial issues surrounding the process of genetic testing. In addition, there have been major discoveries related to other hereditary cancer syndromes, including Lynch syndrome (germline mutation in DNA mismatch repair genes), Li–Fraumeni syndrome (germline mutation in p53), and Cowden syndrome (germline mutation in PTEN), all of which have gynecologic cancers as part of the spectrum of disease.

Where are we now with this young field of clinical cancer genetics and where do we need to go? How do we manifest the power of genetic testing to ultimately decrease the mortality and morbidity of gynecologic cancers? One of the fundamental paradigms associated with clinical genetic testing is that although the family member who may benefit most from genetic testing is the unaffected individual, the person who needs to undergo the testing first is the person with cancer. For a young woman who has witnessed her mother go through treatment for ovarian cancer and wants to undergo genetic testing to see if she is at risk, the genetic counselor will routinely say, "In order for the test to be meaningful, your mother who had ovarian cancer should have genetic testing first." If a mutation is identified in the mother with cancer, then the daughter, who is at 50% risk of inheriting the mutation, can be tested for that specific mutation. There is a very definite answer: yes or no. However, if the daughter who has not had cancer undergoes testing first, the interpretation of the results is more difficult. A positive result is positive, but a negative result could mean (i) her mother did not have a BRCA mutation, that is, she did not have a hereditary form of ovarian cancer; (ii) her mother did have a BRCA mutation, but the daughter did not inherit it; and (iii) there is an as yet unidentified mutation in her family that the testing was unable to detect. Because of the importance of performing the genetic testing on a person with cancer, first we need to ask ourselves, How good are we at asking our cancer patients about family history? And how good are we about referring appropriate patients for genetic counseling and testing? My sense at my own institution and by speaking with my colleagues at other institutions is that we are not systematically screening our patients with ovarian and endometrial cancer for hereditary cancer syndromes.

Herein lies the purpose of this book. There is a need for practical education for physicians caring for women with gynecologic cancers to understand the role of the cancer doctor in identifying which patients may have a hereditary cancer syndrome. Today the implications of testing the ovarian cancer patient for a BRCA mutation include the ability to help not only the family members but also the patient herself. We know that having a BRCA mutation confers an improved survival in women with ovarian cancer. In addition, new therapies for the treatment of ovarian cancer are currently in clinical trials that are targeted toward women with ovarian cancer who have a BRCA mutation. The clinician needs to know how to identify which ovarian or endometrial cancer patients may have a hereditary predisposition, how to refer that person for genetic counseling, and how to manage that patient if her genetic test is positive. For clinicians including obstetrician-gynecologists, internists, family practitioners, and nurse practitioners, who care for women without cancer who are mutation carriers, this book provides education and information regarding risk-reducing strategies and options for screening and early detection. I would appreciate feedback from readers.

I have many people to thank for assisting me with this project. First, I am grateful to the authors of each chapter for delivering important information in a clear and approachable manner. Second, thanks to Molly Daniels, our GYN genetic counselor, for her helpful insights and continued partnership and to Jeannette Upshaw, who helped keep me and all involved with this project on track. Third, thanks to Dr. Gershenson and my colleagues at M.D. Anderson, who contribute so much to the work I do. Thanks to Robin Lacour, Shannon Westin, and Larissa Meyer, fellows who assisted in the writing of the Learning Points and Case Reports, and to all the fellows who have participated in my research. I owe a great deal to my patients, who inspire me in my research on hereditary cancers. Every patient has an awe-inspiring tale, and I never tire of hearing them. Finally, a word of deep gratitude to my husband Charlie and my children Ned, David, and Kate—thank you for your constant love and the joy you bring to my life.