Eric J. Topol, MD
May 06, 2015
Mammography Is a Recipe for Net Harm
The medical community prides itself on evidence to drive important decision-making. But when the evidence is contrary to entrenched medical practice, it has a hard time coming to terms. Such is the case for mammography recommendations. All of the data now available point to significant net harm—far more risk than benefit— for routine mammography. If this were a drug, the US Food and Drug Administration (FDA) would never approve it. Last year, the Swiss Medical Board, after reviewing all of the data, recommended abolishing mammography.
But last week, the US Preventive Services Task Force (USPSTF) issued new draft recommendations regarding who should undergo screening and how often. There was no support for routine screening in women younger than 50 or older than 74 years. But the recommendation for women aged 50-74 years is to undergo mammography every 2 years. There has never been a large study of mammography done every 2 years, so the basis for that periodicity of screening is questionable. But there are abundant data for annual screening and they are not at all supportive of continuing this practice.
A systematic assessment based on all of the evidence available from 1960-2014 showed that for 10,000 women in their 50s, who are screened annually over the course of a decade, there are only 5 individuals whose breast cancer deaths are prevented. But there are over 6100 women who have false-positive tests that lead to additional imaging and unnecessary biopsy procedures. This > 60% false-positive rate is an indicator of a remarkably poor test with respect to accuracy, no less the large toll of emotional turmoil that it engenders.
What about all of the biopsies that are performed? A recent study also underscored yet another level of imprecision: the problem of interpreting biopsies by pathologists when there is agreement among three experts about the presence of cancer only 75% of the time. Added to the net harm of mammography is overdiagnosis, which occurs in 20%-30% of women who have an abnormal result but in whom cancer would not be apparent unless the scan was performed.
Nevertheless, these women often undergo surgery and receive chemotherapy or radiation (or a combination of all of these treatments), even though there is little to no impact on prognosis. Such individuals typically believe that their lives have been saved even though the data point against that assertion. A Harvard study published in the current issue of Health Affairs demonstrated that the cost of these false-positive studies and overdiagnosis was approximately $4 billion per year. This is on top of the current US costs of annual mammography of nearly $10 billion.
It is time to reboot how we screen for breast cancer. Until now, the use of mass screening suggests that we are unable to differentiate the risk in any given individual. So instead of a smart approach that uses family history and genetics, we have dumbed it down and treated all women the same. As a result, we have come to rely on a test that is notoriously inaccurate but has become a fixed part of American medical practice since it was introduced almost 50 years ago. With the tens of millions of low-risk women unnecessarily undergoing screening each year, any test would be vulnerable to a high rate of false positives. That applies to higher-resolution scans, too, such as magnetic resonance, digital mammography and ultrasound. Indeed, there is a better path forward.
Why Family History and Genomics Matter
There is strong evidence that family history is critical for defining risk. Beyond family history, we have the ability to sequence the genes known to carry high-risk mutations. Dr Mary-Claire King, who discovered the BRCA1 gene, has advocated that all women age 30 and older should be screened for mutations that carry a high risk for breast and ovarian cancer. She’s right. And at some point, why not add men, who unknowingly can pass along important BRCA mutations to their daughters?
We didn’t have a way to widely implement such a recommendation until this past week when a collaboration, called BRCA Share, was reported between the two largest central lab companies—Laboratory Corporation of America and Quest Diagnostics —as was the announcement of a new genetic testing company called Color Genomics. For $249, Color Genomics is offering, via a saliva sample, sequencing of the BRCA genes along with 17 other genes that carry a high risk for familial cancer. For 1 year of mammography costs in the United States, we could now perform such genetic testing for over 56 million women. The unrelenting plummeting of the cost of sequencing—and a much more expansive approach to the whole genome (instead of just ~20 genes)—is just around the corner.
When she announced her choice to undergo bilateral mastectomy in 2013, Angelina Jolie wrote in an op-ed in The New York Times : “But today it is possible to find out through a blood test whether you are highly susceptible to breast and ovarian cancer, and then take action. Life comes with many challenges. The ones that should not scare us are the ones we can take on and take control of.” Just a couple of years later, the Angelina Effect on heightening awareness and the US Supreme Court decision against Myriad Genetics’ BRCA testing monopoly have introduced exciting opportunities for adopting a new approach. We shouldn’t be scared of it. It doesn’t even require a blood test anymore. We should take it on, study it, and exploit the progress in genomic science to develop an intelligent, evidence-based, and economically attractive precise path forward.
1.Biller-Andorno N, Jüni P. Abolishing mammography screening programs? A view from the Swiss medical board. N Engl J Med. 2014; 370:1965-196. Abstract
2.Elmore JG, Kramer BS. Breast cancer screening toward informed decisions. JAMA. 2014;311:1298-1299. Abstract
3.Elmore JG, Longton GM, Carney PA, et al. Diagnostic concordance among pathologists interpreting breast biopsy specimens. JAMA. 2015;313:1122-1132. Abstract
4.Ong MS, Mandl KD. National expenditure for false-positive mammograms and breast cancer overdiagnoses estimated at $4 billion a year. Health Aff (Millwood). 2015:34;576-583. Abstract
5.King, MC, Levy-Lahad E, Lahad A. Population-based screening for BRCA1 and BRCA2. 2014 Lasker Award. JAMA. 2014;312:1091-1092. Abstract