Analysis of two Annals papers on benefits of mammography in younger women

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Results of two studies published in the Annals of Internal Medicine point to benefits of biennial mammography screening starting age 40 for women at increased risk.

One evaluated data from 66 published articles and from the Breast Cancer Surveillance Consortium.  The authors’ conclusion:

Extremely dense breasts and first-degree relatives with breast cancer were each associated with at least a 2-fold increase in risk for breast cancer in women aged 40 to 49 years. Identification of these risk factors may be useful for personalized mammography screening.

The second study tried to assess “tipping the balance of benefits and harms to favor screening mammography starting at age 40.”  The lead author concluded:

“The evidence suggests that for women at twice the average risk for breast cancer, biennial screening beginning at age 40 has more benefits than harms,” said study lead author Nicolien T. van Ravesteyn, MSc, of the Department of Public Health, Erasmus MC, Rotterdam, The Netherlands. “These results provide important information toward developing more individualized, risk-based screening guidelines.”

Dr. Otis Brawley, chief medical and scientific officer of the American Cancer Society, wrote an accompanying editorial.  Excerpts:

“I worry that the public perceives mammography as a better technology than it actually is. Mammography screening is often promoted for its benefit. Unfortunately, many do not appreciate its limitations. Truth be told, it cannot avert all or even most breast cancer deaths. There are also tradeoffs. Mammography, like every screening test, has a potential for harm, and one must carefully weigh the harm–benefit ratio for a specific woman or a specific population of women (such as those aged 40 to 49 years) before advising use of the test. The harms associated with mammographic screening include false-positive results, false-positive biopsy results, radiation exposure, false-negative results and false reassurance, pain related to the procedure, overdiagnosis (that is, diagnosis of tumors that are of no threat), and overtreatment. False-positive results are the most common and easily quantifiable harm. On the basis of statistics specific to U.S. practice patterns, about half of women getting an annual mammogram for 10 years starting at age 40 years will have at least 1 false-positive result that requires additional testing. More than 5% will get a biopsy during that time.

…These studies also demonstrate that questions about annual versus biennial screening are legitimate but unsettled. The Cancer Intervention and Surveillance Modeling Network consistently shows that annual screening of women in their 40s marginally increases the number of lives saved while substantially increasing harms. This means that patients and their physicians need to make value judgments regarding the harms and benefits.
In the future, more emphasis will be placed on riskbased screening guidelines tailored to the individual. There may be recommendations that some women at very high risk get annual testing, some at intermediate risk get biennial testing, and some at normal risk start screening at a later age. This will be challenging because many health care providers and members of the lay community do not understand screening and the concept of risk. Specific tools designed to educate them need to be developed and rigorously assessed. Ultimately, the preferences of individual women, recognizing the potential for harm and benefit, should be respected.”

For more perspective, I asked Russell Harris, MD, MPH of the University of North Carolina, to analyze the new studies.  He wrote:

“These are well-conducted studies that try to move us toward more efficient screening for breast cancer.  Certainly we are all in favor of that.  At present, our screening is based on the fact that the risk of breast cancer and breast cancer mortality increases with age; thus, we base starting screening on age.  This is the famous “start at age 40 vs start at age 50” debate we have been having for many years.  These investigators suggest that perhaps there are risk factors beyond age that could allow us to better target the women who could benefit from screening.  It is a good idea.

Unfortunately, the first paper (Nelson et al) shows that we just don’t know enough about the factors that increase or decrease the risk of breast cancer to be able to use this proposed strategy.  This causes the second paper (van Ravesteyn) to make some statements that may be misunderstood and confusing.

Nelson (the first paper) systematically reviews studies of the risk of breast cancer, finding that, other than age, extremely dense breasts on mammogram and presence of first-degree family history of breast cancer are the most important risk factors.  It is important to know that dense breasts on mammography may well reduce the ability of mammography to detect breast cancer, and that very few women will have 2 or more first degree relatives who have been diagnosed with breast cancer (which is the group that has a really substantial increased risk).  The problem is that neither of these factors increase risk more than about two-fold.  These factors would be much more useful if they increased risk by 15 or 20-fold.

Van Ravesteyn et al (the second paper) then use their models to find that if we could identify women in their 40s whose risk is more than 3 times usual risk, then the number of lives extended by screening those women in their 40s would be about the same as the number in their 50s whose lives are extended by screening.  (In neither case is this a large number of women.)  Unfortunately, they do not adequately address the issue of the harms of screening, especially including overdiagnosis, a problem that many people far underestimate. Because the models do not adequately address harms, and because we don’t know how much benefit there would be (if any) from screening women in their 40s with dense breasts, and because there are so few women in their 40s with 2 or more first degree relatives, this strategy really doesn’t get us very far toward making screening more efficient.  The best strategy is still what the USPSTF recommended: individual discussions between patient and medical team to develop an individual approach.

Some people who have wanted to start screening mammography at age 40 will read these papers and find a justification for starting early.  A better interpretation of these studies is that we still need better risk tools that help us become more efficient with breast cancer screening – and this means not only finding women whose risk is high enough that screening makes good sense AND also finding women in their 50s and 60s whose risk is low enough that screening doesn’t make sense.  Then we can truly say we are more efficient – screening women more likely to benefit and NOT screening women more likely to be harmed.”

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