Wednesday, October 29, 2014
All Ashkenazi Jewish women should be tested for BRCA
Mutations in two genes called BRCA1 and BRCA2 greatly increase the risk of breast and ovarian cancer. Last year I wrote about Angelina Jolie’s discovery that she carries a harmful BRCA1 mutation and her decision to have preventive double mastectomy.
In the general population mutations in these genes are quite rare, but among Ashkenazi Jews these mutations are much more prevalent. One in 40 Ashkenazi Jews carries a mutation in BRCA1 or BRCA2. In the Ashkenazi population one in 9 cases of breast cancer and 2 in 5 cases of ovarian cancer involve mutations in a BRCA gene.
Identifying women with BRCA mutations who are at high risk of breast and ovarian cancer isn’t just an exercise in predicting trouble. Preventive action can be taken. As Angelina Jolie’s story teaches us, preventive surgery that removes the breasts and ovaries greatly decreases the risk. Mastectomy, of course, is difficult physically and psychologically. For some women at very high risk, intensive screening with mammograms and breast MRI offers some level of protection without resorting to surgery.
Thus far genetic testing for these mutations has only been recommended for Ashkenazi women with a strong family history of breast or ovarian cancer. That’s because BRCA mutation carriers with a family history of breast or ovarian cancer were the only group studied and found to have increased cancer risk.
But if the BRCA mutations themselves cause breast and ovarian cancer, why should family history matter? Why not test everyone who might have these mutations? The answer is that the risk of cancer in BRCA mutation carriers without a family history of cancer has never been measured. Without knowing that, it is possible that the mutation carriers who have a family history of cancer have an increased risk because of some other shared genes that have yet to be identified or because of some shared exposure to cancer-causing agents in the environment. That is, without knowing the risk of BRCA mutation carriers who do not have a family history of cancer, we can’t be sure if the BRCA mutations are the cause of increased risk, or simply a marker for some other cause that is yet unknown.
A study carried out in Israel and published this month in the Proceedings of the National Academy of Sciences sought to answer this question in an ingenious way. The study enrolled about 8,000 Israeli Ashkenazi men without a history of cancer and tested them for BRCA mutations. 175 of them were found to carry harmful BRCA mutations. The first degree female relatives of these 175 men (their mothers, sisters and daughters) were invited to undergo BRCA testing. This identified 211 female BRCA mutation carriers, many of whom had no family history of breast cancer. By studying the medical histories of the identified female mutation carriers, their risk of ovarian and breast cancer was calculated.
The results showed that a woman with a BRCA1 mutation has an 83% risk of developing breast or ovarian cancer by age 80. BRCA2 mutation carriers have a 76% risk of breast or ovarian cancer by age 80. These numbers are very similar to those from studies that only counted women with strong family histories of cancer. That means that a family history is not necessary to identify women who benefit from screening, and suggests that all Ashkenazi Jewish women should be tested for BRCA mutations.
National groups that evaluate scientific data and make testing recommendations like the American Cancer Society and the US Preventive Services Task Force haven’t had a chance to digest the news yet. They still recommend BRCA testing only for women with strong family histories of breast and ovarian cancer.
A medical geneticist I spoke with said that BRCA testing costs about $400 and is generally not covered by insurance. If you’d like to pursue testing, the first step is asking your doctor to refer you to a medical geneticist for pre-testing counseling.
Population screening for specific genetic diseases, like Tay-Sachs, has proven in the past to make enormous reductions in the societal burden of disease. Screening all Ashkenazi Jewish women for BRCA holds out the promise of similar gains against breast and ovarian cancer.
Study of Jewish Women Shows Link to Cancer Without Family History(New York Times)
Israeli research team: Screen all Ashkenazi-Jewish women for BRCA mutations (The Jerusalem Post)
Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2 (Proceedings of the National Academy of Sciences, abstract free, full article by subscription)
Understanding Angelina (My post from 2013 explaining the BRCA testing recommendations at that time)
Albert Fuchs, MD, FACP, graduated from the University of California, Los Angeles School of Medicine, where he also did his internal medicine training. Certified by the American Board of Internal Medicine, Dr. Fuchs spent three years as a full-time faculty member at UCLA School of Medicine before opening his private practice in Beverly Hills in 2000. Holding privileges at Cedars-Sinai Medical Center, he is also an assistant clinical professor at UCLA's Department of Medicine. This post originally appeared at his blog.
Contact ACP Internist
Send comments to ACP Internist staff at firstname.lastname@example.org.
- Ebola question: From the mailbag
- Our health, on fire: the #UseWhatWeKnow campaign
- Ebola preparedness and the Lab
- Avoid premature performance standards
- What I learned from Ebola
- The 'nocebo effect,' statins, and Dr. Ben Goldacre...
- Ebola: The questions keep coming
- Which medical specialty should medical students ch...
- Medicare follies, or, the Annual Wellness Visit
- Clinical practice guidelines, autism, and ordering...
Members of the American College of Physicians contribute posts from their own sites to ACP Internistand ACP Hospitalist. Contributors include:
Albert Fuchs, MD, FACP, graduated from the University of California, Los Angeles School of Medicine, where he also did his internal medicine training. Certified by the American Board of Internal Medicine, Dr. Fuchs spent three years as a full-time faculty member at UCLA School of Medicine before opening his private practice in Beverly Hills in 2000.
And Thus, It Begins
Amanda Xi, ACP Medical Student Member, is a first-year medical student at the OUWB School of Medicine, charter class of 2015, in Rochester, Mich., from which she which chronicles her journey through medical training from day 1 of medical school.
Ira S. Nash, MD, FACP, is the senior vice president and executive director of the North Shore-LIJ Medical Group, and a professor of Cardiology and Population Health at Hofstra North Shore-LIJ School of Medicine. He is Board Certified in Internal Medicine and Cardiovascular Diseases and was in the private practice of cardiology before joining the full-time faculty of Massachusetts General Hospital.
Zackary Berger, MD, ACP Member, is a primary care doctor and general internist in the Division of General Internal Medicine at Johns Hopkins. His research interests include doctor-patient communication, bioethics, and systematic reviews.
Controversies in Hospital
Run by three ACP Fellows, this blog ponders vexing issues in infection prevention and control, inside and outside the hospital. Daniel J Diekema, MD, FACP, practices infectious diseases, clinical microbiology, and hospital epidemiology in Iowa City, Iowa, splitting time between seeing patients with infectious diseases, diagnosing infections in the microbiology laboratory, and trying to prevent infections in the hospital. Michael B. Edmond, MD, FACP, is a hospital epidemiologist in Iowa City, IA, with a focus on understanding why infections occur in the hospital and ways to prevent these infections, and sees patients in the inpatient and outpatient settings. Eli N. Perencevich, MD, ACP Member, is an infectious disease physician and epidemiologist in Iowa City, Iowa, who studies methods to halt the spread of resistant bacteria in our hospitals (including novel ways to get everyone to wash their hands).
db's Medical Rants
Robert M. Centor, MD, FACP, contributes short essays contemplating medicine and the health care system.
Suneel Dhand, MD, ACP Member
Suneel Dhand, MD, ACP Member, is a practicing physician in Massachusetts. He has published numerous articles in clinical medicine, covering a wide range of specialty areas including; pulmonology, cardiology, endocrinology, hematology, and infectious disease. He has also authored chapters in the prestigious "5-Minute Clinical Consult" medical textbook. His other clinical interests include quality improvement, hospital safety, hospital utilization, and the use of technology in health care.
Juliet K. Mavromatis, MD, FACP, provides a conversation about health topics for patients and health professionals.
Dr. Mintz' Blog
Matthew Mintz, MD, FACP, has practiced internal medicine for more than a decade and is an Associate Professor of Medicine at an academic medical center on the East Coast. His time is split between teaching medical students and residents, and caring for patients.
Toni Brayer, MD, FACP, blogs about the rapid changes in science, medicine, health and healing in the 21st century.
Vineet Arora, MD, FACP, is Associate Program Director for the Internal Medicine Residency and Assistant Dean of Scholarship & Discovery at the Pritzker School of Medicine for the University of Chicago. Her education and research focus is on resident duty hours, patient handoffs, medical professionalism, and quality of hospital care. She is also an academic hospitalist.
John H. Schumann, MD, FACP, provides transparency on the workings of medical practice and the complexities of hospital care, illuminates the emotional and cognitive aspects of caregiving and decision-making from the perspective of an active primary care physician, and offers behind-the-scenes portraits of hospital sanctums and the people who inhabit them.
Ryan Madanick, MD, ACP Member, is a gastroenterologist at the University of North Carolina School of Medicine, and the Program Director for the GI & Hepatology Fellowship Program. He specializes in diseases of the esophagus, with a strong interest in the diagnosis and treatment of patients who have difficult-to-manage esophageal problems such as refractory GERD, heartburn, and chest pain.
Mike Aref, MD, PhD, FACP, is an academic hospitalist with an interest in basic and clinical science and education, with interests in noninvasive monitoring and diagnostic testing using novel bedside imaging modalities, diagnostic reasoning, medical informatics, new medical education modalities, pre-code/code management, palliative care, patient-physician communication, quality improvement, and quantitative biomedical imaging.
William Hersh, MD, FACP, Professor and Chair, Department of Medical Informatics & Clinical Epidemiology, Oregon Health & Science University, posts his thoughts on various topics related to biomedical and health informatics.
David Katz, MD
David L. Katz, MD, MPH, FACP, is an internationally renowned authority on nutrition, weight management, and the prevention of chronic disease, and an internationally recognized leader in integrative medicine and patient-centered care.
Richard Just, MD, ACP Member, has 36 years in clinical practice of hematology and medical oncology. His blog is a joint publication with Gregg Masters, MPH.
Kevin Pho, MD, ACP Member, offers one of the Web's definitive sites for influential health commentary.
Michael Kirsch, MD, FACP, addresses the joys and challenges of medical practice, including controversies in the doctor-patient relationship, medical ethics and measuring medical quality. When he's not writing, he's performing colonoscopies.
Elaine Schattner, MD, FACP, shares her ideas on education, ethics in medicine, health care news and culture. Her views on medicine are informed by her past experiences in caring for patients, as a researcher in cancer immunology, and as a patient who's had breast cancer.
Mired in MedEd
Alexander M. Djuricich, MD, FACP, is the Associate Dean for Continuing Medical Education (CME), and a Program Director in Medicine-Pediatrics at the Indiana University School of Medicine in Indianapolis, where he blogs about medical education.
Rob Lamberts, MD, ACP Member, a med-peds and general practice internist, returns with "volume 2" of his personal musings about medicine, life, armadillos and Sasquatch at More Musings (of a Distractible Kind).
David M. Sack, MD, FACP, practices general gastroenterology at a small community hospital in Connecticut. His blog is a series of musings on medicine, medical care, the health care system and medical ethics, in no particular order.
Reflections of a Grady
Kimberly Manning, MD, FACP, reflects on the personal side of being a doctor in a community hospital in Atlanta.
The Blog of Paul Sufka
Paul Sufka, MD, ACP Member, is a board certified rheumatologist in St. Paul, Minn. He was a chief resident in internal medicine with the University of Minnesota and then completed his fellowship training in rheumatology in June 2011 at the University of Minnesota Department of Rheumatology. His interests include the use of technology in medicine.
Technology in (Medical)
Neil Mehta, MBBS, MS, FACP, is interested in use of technology in education, social media and networking, practice management and evidence-based medicine tools, personal information and knowledge management.
Peter A. Lipson,
Peter A. Lipson, MD, ACP Member, is a practicing internist and teaching physician in Southeast Michigan. The blog, which has been around in various forms since 2007, offers musings on the intersection of science, medicine, and culture.
Why is American Health Care So Expensive?
Janice Boughton, MD, FACP, practiced internal medicine for 20 years before adopting a career in hospital and primary care medicine as a locum tenens physician. She lives in Idaho when not traveling.
World's Best Site
Daniel Ginsberg, MD, FACP, is an internal medicine physician who has avidly applied computers to medicine since 1986, when he first wrote medically oriented computer programs. He is in practice in Tacoma, Washington.
Other blogs of note:
American Journal of
Also known as the Green Journal, the American Journal of Medicine publishes original clinical articles of interest to physicians in internal medicine and its subspecialities, both in academia and community-based practice.
A collaborative medical blog started by Neil Shapiro, MD, ACP Member, associate program director at New York University Medical Center's internal medicine residency program. Faculty, residents and students contribute case studies, mystery quizzes, news, commentary and more.
Michael Benjamin, MD, ACP member, doesn't accept industry money so he can create an independent, clinician-reviewed space on the Internet for physicians to report and comment on the medical news of the day.
The Public Library of Science's open access materials include a blog.
One of the most popular anonymous blogs written by an emergency room physician.