Joi L. Morris - Positive Results: Making the Best Decisions When Youre at High Risk for Breast or Ovarian Cancer

A book like this is never the work of just its authors. Many others have helped Positive Results on its journey. The first and largest thank you must go to our agent, Gina Maccoby, who went above and beyond the call of duty to help these first-time authors find their voice, and for tirelessly working to find the right publishing house for this book. We also thank all of the men and women who gave their time and shared their stories. They are too numerous to name, and many of them do not wish to be named. We also wish to thank those who reviewed portions of the manuscript for accuracy, including Steven Narod, MD; Ilana Cass, MD; Donald S. Cohen, MD; Kristi M. Funk, MD; Howard C. Mandel, MD; Leslie Memsic, MD; Joan Osder, MD; Bruce Shragg, MD; R. Kendrick Slate, MD; Margaret Snow, MD; Kent Taylor, PhD; and Rachel Beller, RD. Additional thanks go to Joyce Canada, Ann Cummings, Whitney Ducaine, Eileen Escarce, Jeanne Homer, and Steve Kandel. Special thanks go to our husbands and our children, who encouraged us, provided inspiration, and put up with Mom being in front of the computer for long hours. Finally, we wish to thank everyone at Prometheus Books for helping our dream become reality.

As an outreach coordinator for FORCE, Facing Our Risk of Cancer Empowered, I get lots of questions from women who want to know, What is the right thing to do if you have a BRCA mutation? I hope that you realize from reading this book that most of the decisions you must make on this high-risk journey do not have a single right answer. Some things are clear, such as the need to remove your ovaries to reduce the overwhelmingly high risk of ovarian cancer. But the decisions of when to have surgery, what type of surgery to have, whether to use hormone replacement therapy, and what type of hormones to use are yours and yours alone. By all means, solicit advice and opinions from the experts, from your doctors. But remember that what may be the right decision for one woman may not be for another. The right decision is the one that fits your life, your circumstances, and your risk tolerance. I often say the right decision is the one that allows you to sleep at night.

I do not wish this journey on anyone; it is difficult and fraught with anxiety. But I have met some truly amazing women along the waystrong, vibrant, courageous women. My life is richer because they are in it. The women and men profiled in these pages exhibited extraordinary courage and strength. I have no doubt that you also have the strength and courage to make the tough decisions that lie ahead on your own journey.

If you have a strong family history of breast cancer, or of any of the other diseases associated with these genes, they should be investigated as a possible cause of the increased cancer in your family. Keep in mind, however, that these genetic changes are rarer than mutations on BRCA1 or BRCA2; they occur in only one in ten thousand to one in one million individuals.

TP53/Li-Fraumeni Syndrome is a hereditary cancer syndrome first described in the 1960s by two surgeons (Frederick Li and Joseph Fraumeni Jr.); more than 70 percent of cases are due to mutations on the TP53 gene (sometimes referred to as p53). The classic characteristics of Li-Fraumeni Syndrome are a combination of (1) very early onset of breast cancer, (2) soft tissue tumors known as sarcomas, and (3) carcinoma of the adrenal glands. Originally, all three symptoms were required for a diagnosis of Li-Fraumeni. More recently, TP53 mutations have been found in families not meeting the original strict clinical diagnosis criteria, and a Li-Fraumeni-like syndrome with more broadly inclusive criteria has emerged. This is very different from BRCA mutations, which tend to be quite stable from one generation to the next. New or spontaneous mutations are rare in the BRCA genes. Because TP53 changes can be responsible for a significant number of breast cancers in young women, TP53 gene testing should always be considered in a woman who has a very early onset of breast cancer and who tests negative for a BRCA mutation.

PTEN/Cowden Syndrome is a cancer-predisposition syndrome arising from mutations in the PTEN gene, which is associated with increased risk of breast, thyroid, and uterine cancer as well as a variety of benign tumors, such as multinodular goiter, fatty tumors of the skin (called lipomas), and growths in the mouth. Some studies have found up to 5 percent of breast cancers under age forty are associated with a hereditary PTEN mutation. Cowden syndrome is unique in that it has characteristic clinical features including benign polyps of the colon (called hamartomas), warty growths of the skin, and an enlarged head circumference. Because of its clear identifying characteristics, any doctor considering inherited breast cancer risk should do a thorough clinical examination and family history in order to rule out the possibility of a PTEN mutation.

CDH1/E-Cadherin gene mutations are often found in sporadic cancers and are frequently used in the laboratory to distinguish lobular breast cancer from ductal breast cancer. A very specific form of hereditary stomach cancer, diffuse gastric cancer, is caused by mutations in CDH1, and female carriers are at greatly increased risk for lobular breast cancer. If your family has a history of gastric cancer and lobular breast cancer, testing for CDH1 is appropriate.

STK11/Peutz-Jehgers Syndrome is a multiple-cancer-susceptibility syndrome that also has clinical features. PJS, which is due to mutations in the STK11 gene, causes multiple colon polyps, unusual pigmentation of the mouth and hands, and a predisposition to cancer of the small and large intestines, breasts, and pancreas. PJS is extremely rare but should always be considered in cases of very early breast cancer. PJS can be ruled out through a clinical examination and colonoscopy.

CHEK2 makes a regulatory protein that is activated in response to radiation and other agents that cause breaks in DNA. CHEK2 was dubbed the breast-colon gene because it appeared to increase the risk of breast and colon cancer in both men and women, as well as prostate cancer in men.

ATM is the gene responsible for a recessive genetic disorder known as Ataxia Telangectasia, which affects children and causes gait problems, characteristic small broken blood vessels (telangectasias), and various cancers. Mothers of affected children who are carriers but unaffected themselves have an increased incidence of breast cancer, about double the general population risk.

PALB2 is a partner and localizer of BRCA2. The PALB2 gene was originally identified as producing a BRCA2-interacting protein and it was thought to be a modifier gene in families with BRCA2 mutations. However, several mutations in PALB2 have been associated independently with an increased risk of breast cancer. A founder mutation, 1592delT, has been reported in Finland among high-risk families who are BRCA negative (families without any BRCA mutations). The cancer risk varies among studies, from moderate (like in CHEK2) to mimicking BRCA with up to a 40 percent lifetime breast cancer risk.