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By Jeffrey T. Jensen, MD, MPH
Leon Speroff Professor and Vice Chair for Research, Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland
Dr. Jensen reports he is is a consultant for Teva Pharmaceuticals and MicroChips; and is a consultant for and receives grant research support from HRA Pharma, Bayer Healthcare, Merck, Agile Pharm, Population Council, AbbVie, Evofem, and ContraMed.
SYNOPSIS: The U.S. Preventive Services Task Force recently released updates to the 2009 recommendations on breast cancer screening. Additional studies published since the last review strengthen the conclusion that mammography screening results in a reduction in the risk of death from breast cancer. The available evidence supports that benefits of screening mammography exceed harm when screening begins at age 50 and is conducted every two years through age 74.
In November 2009, the U.S. Preventive Services Task Force (USPSTF) released revised recommendations on breast cancer screening that made front-page news. These recommendations, based on a systematic review of the literature, sought to balance the potential benefits of screening mammography with risk and harm. The report left women’s health professional groups and breast cancer patient advocacy groups stunned. The USPSTF recommended that women start mammogram screening at age 50, and continue with biannual screening until age 75. These contrasted sharply with the recommendations from the American College of Obstetricians and Gynecologists (ACOG), the American College of Surgeons, and the American College of Radiologists, all of whom recommended annual mammograms beginning at 40 with no fixed upper age limit. While some professional groups (American Academy of Family Physicians, American College of Physicians) adopted the USPSTF guidelines, the recommendations became deeply politicized. Some saw the report as a government plot to save on health care dollars at the expense of women’s health.
The issue threatened to derail the Affordable Care Act, as a key provision was the mandate that private insurers cover procedures for which the USPSTF issued a grade of “A” (high certainty that the net benefit is substantial) or “B” (high certainty that the net benefit is moderate or moderate certainty that the net benefit is moderate to substantial) recommendation, but not lower grades. Fierce lobbying led to passage of a convoluted law that created an exemption for mammography to ensure coverage for annual screening tests, and for exams for women aged 40 to 49 years (a grade “C” — benefit not clear — recommendation in 2009). However, a “Cinderella” clause in the law required this exemption to expire once the USPSTF issued new recommendations.
Last spring, the USPSTF released the draft of their updated recommendations to public comment. In making the revised recommendations, the USPSTF took into account new information that strengthened the conclusions from 2009. The outcry from advocates was immediate and forceful. Like me, you may have received an email from Hologic, a leading manufacturer of mammography equipment, urging you to contact your congressman in support of legislation to ensure access to mammography and supplemental screens. This lobbying must have worked; a rider extending the exception for the grade “C” recommendation for private insurance coverage of screening mammography was inserted into the Consolidated Appropriations Act omnibus spending bill that passed Congress last December1 (impressive, given the inaction of Congress on so many other pressing issues). This congressional action maintaining coverage apparently cleared the way for publication of the revised recommendations.
On Jan. 12, 2016, the Annals of Internal Medicine and USPSTF website simultaneously released electronic publication of the new clinical guidance2 along with four original research papers,4,6-8 three reviews,3,9,10 four editorials,1,11-13 and one patient summary.5 In this issue, I want to take on the recommendations for screening. Next month, I will discuss the potential harms of screening, and the risks and benefits of supplemental screening for women with dense breasts.
The USPSTF recommends biennial screening mammography for all women aged 50 to 74 years (B recommendation).2 For women < 50 years of age, the recommendation for screening mammography received a “C” grade (moderate certainty that the net benefit of screening, while positive, is small). The current evidence was deemed insufficient to assess the balance of benefits and harms of screening mammography in women aged 75 years or older (I statement, grade of “I” = insufficient).
The USPSTF also evaluated supplemental imaging modalities. It concluded that the evidence for benefits and harms of digital breast tomosynthesis (DBT) as a primary screening method for breast cancer was insufficient (I statement). The task force also found the current evidence insufficient to assess the benefits and harms of adjunctive screening modalities (breast ultrasonography, magnetic resonance imaging [MRI], DBT, or other methods) in women identified to have dense breasts on an otherwise negative screening mammogram (I statement).
The target population for the USPSTF recommendation includes women ≥ 40 years of age without clinical breast abnormalities or symptoms that would trigger the order of a diagnostic test. The recommendations do not apply to women at high risk of breast cancer (i.e., preexisting breast cancer or high-risk breast lesions, hereditary genetic syndromes associated with breast cancer, or previous large doses of chest radiation before age 30 years). The recommendations do apply to women with standard risk factors such as positive family history (without hereditary genetic syndrome).3
The USPSTF found adequate evidence that mammography screening reduces breast cancer mortality in women aged 40 to 74 years.3 The number of breast cancer deaths averted increases with age; women aged 40 to 49 years benefit the least and women aged 60 to 69 years benefit the most. At age 70, the benefit declines and after age 75 there is insufficient evidence of benefit. This increased benefit associated with age reflects the fact that age is the most important risk factor for breast cancer. In other words, the increased benefit observed with age is due to the increase in absolute risk. Overall, a meta-analysis of mammography trials indicated a protective effect. The relative risk (RRs) reduction for breast cancer mortality was small and nonsignificant for women aged 39 to 49 years (RR, 0.92; 95% confidence interval [CI], 0.75-1.02), but strengthened and became significant for women 50 to 59 years (RR, 0.86; 95% CI, 0.68-0.97) and for those 60 to 69 years (RR, 0.67; 95% CI, 0.54-0.83). Although the point estimate for those aged 70 to 74 years was protective (RR, 0.8; 95% CI, 0.51-1.28), the CI broadly overlaps 1.0. Looking at this another way, screening mammography would be expected to avert three deaths in 10,000 women aged 39-49 screened over 10 years, 8 deaths among 10,000 women 50-59, 21 deaths per 10,000 aged 60-69, and 13 deaths among women 70-74.
A major limitation of the conclusions is the use of outdated imaging technologies and treatments in the majority of studies that supplied evidence for the meta-analysis. However, it remains controversial whether improved imaging contributes to a meaningful reductions in mortality or simply a greater risk of overdiagnosis (more on this next month).
The take home message from the USPSTF review can be summarized as follows: Although breast cancer mortality is generally reduced with mammography screening, estimates are not statistically significant at all ages (in particular for women < 50 years and > 70 years), and the magnitudes of effect are small, ranging from a low of 8% in women ages 40-49 to a high of 33% in women ages 60-69. Overall, mammography screening will prevent < 1 death per 1000 women screened over 10 years for all age groups except women aged 60-69.
In making recommendations for screening tests, the USPSTF considered both benefits and harms. The published recommendations reflect the best available evidence. Although only screening every 2 years for women at average risk aged 50-74 years received a “B” grade, the task force did not recommend against screening women < 50 years or > 75 years of age. Instead, they suggested that women and their health care providers thoughtfully consider the potential benefits and harms of screening. To quote the recommendations “For women in their 40s, the number who benefit from starting regular screening mammography is smaller and the number experiencing harm is larger compared with older women. For women in their 40s, the benefit still outweighs the harms, but to a smaller degree; this balance may therefore be more subject to individual values and preferences than it is in older women. Women in their 40s must weigh a very important but infrequent benefit (reduction in breast cancer deaths) against a group of meaningful and more common harms (overdiagnosis and overtreatment, unnecessary and sometimes invasive follow-up testing, and psychological harms associated with false-positive test results, and false reassurance from false-negative test results). Women who value the possible benefit of screening mammography more than they value avoiding its harms can make an informed decision to begin screening.” A variety of common risk factors may influence the equation. For example, women aged 40 to 49 years who have a known first-degree relative (parent, child, or sibling) with breast cancer should consider initiating screening earlier than age 50 years.
ACOG continues to recommend annual mammograms starting at age 40, and insurers will continue to cover this. This might be the right decision for some women, but not all women. If routine annual mammograms starting at 40 is your standard recommendation, I would encourage you to read the full details of the USPSTF recommendations and associated reports. Unfortunately, this is not a simple discussion anymore. But in my experience, each woman knows what is right for herself.
Financial Disclosure: OB/GYN Clinical Alert’s editor, Jeffrey T. Jensen, MD, MPH, is a consultant for Teva Pharmaceuticals and MicroChips; and is a consultant for and receives grant research support from HRA Pharma, Bayer Healthcare, Merck, Agile Pharm, Population Council, AbbVie, Evofem, and ContraMed. Peer reviewer Catherine Leclair, MD, nurse planners Marci Messerle Forbes, RN, FNP, and Andrea O’Donnell, FNP, executive editor Leslie Coplin, and associate managing editor Jonathan Springston report no financial relationships relevant to this field of study.