Editorials

Screening for Breast Cancer: What to Do with the Evidence

Am Fam Physician. 2007 Jun 1;75(11):1623-1626.

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For many of the conditions we encounter in primary care, there is insufficient evidence to tell us the best course of action. Breast cancer screening is different. We now have nine randomized controlled trials (RCTs) and numerous case-control, cross-sectional, and cohort studies that deal with various aspects of breast cancer screening. It is a comment on the complexity of screening that, even with all of this evidence, controversy remains. We have made progress—there is general agreement about some issues—and yet, for more than 30 years, the medical literature has been a place of continual ferment. Periodically, as new studies and recommendations have been published, news media outlets have been filled with contentious back-and-forth opinions about breast cancer screening.

We are now in the midst of yet another breast cancer screening upheaval. Some recent studies13 and new guidelines from the American College of Physicians (ACP)4 and the American Cancer Society (ACS)5 have raised the issue of breast cancer screening again. What should we in primary care do with this evidence?

The “new” evidence mostly tells us things we already knew. But the decision to screen an individual woman is complex and should be discussed with the patient.

To summarize the latest evidence, an RCT found what we already knew about mam-mography screening for women in their 40s: screening probably decreases breast cancer mortality, but only to a small degree.6 Three short cohort studies found that digital mam-mography and magnetic resonance imaging (MRI) find more breast cancers in some women than does film mammography.13 But none of the studies tells us whether these technologies save more lives or are worth the additional false-positive results, overdiagno-sis, and cost.

Recent studies have also given us a better idea of the harms of screening, especially false-positive mammograms7 and overdiag-nosis.8 False-positive mammograms greatly outnumber actual breast cancers found. In the best study, nearly 50 percent of women had at least one false-positive mammogram over 10 years of screening.9 At a minimum, false-positive mammograms cause temporary anxiety and inconvenience. Some women have longer-lasting worry.

Overdiagnosis occurs most commonly with ductal carcinoma in situ (DCIS), a lesion that is usually detected by mam-mography. It is estimated that less than 50 percent of DCIS lesions progress to invasive breast cancer, yet we treat everyone with DCIS. This means that overdiagnosis leads to overtreatment in a considerable number of women. Some studies estimate that about 10 percent of all breast cancers diagnosed by screening represent overdiagnosis.8

In deciding what to do with this evidence, it may help to summarize the conclusions about breast cancer screening that we are sure about—those that are strongly supported by good evidence. Interestingly, there are only two: (1) screening with mammog-raphy (with or without clinical breast examination) reduces breast cancer mortality to a small extent in women 40 to 49 years of age (15 to 17 percent reduction; number needed to screen [NNS] to prevent one breast cancer death after 14 years = 1,792); and (2) mam-mography reduces breast cancer mortality to a slightly larger extent in women 50 to 69 years of age (22 percent reduction; NNS to prevent one breast cancer death after 14 years = 838).10

These conclusions mean that the balance between benefits and harms is borderline (i.e., benefits and harms are about the same) for women in their 40s and probably positive (i.e., benefits outweigh harms) for women 50 to 70 years of age. We can extend a few women's lives, but we have to put up with many false-positive tests and some degree of overdiagnosis and overtreatment to do it. Because age is a major risk factor for breast cancer, and because there are more false-positive results in younger women, this trade-off between benefits and harms shows screening to be a better deal for women 50 to 70 years of age than for women in their 40s. Some, but not all, of these younger women will want to be screened, whereas most older women will probably choose screening. We have to talk with each patient to understand what is best for her.

Any other conclusions we draw from this evidence are less certain, including the decision about whether to offer screening to women older than 70 years. Because few of these women have been included in RCTs, we are unsure how large a benefit screening confers. Breast cancer risk continues to increase with age, but the presence of comorbid illness and low life expectancy may negate any benefits of mammography. Some healthy women at this age may choose screening, whereas others reasonably may not. Again, discussion (rather than reflexive screening) seems to be the best practice.

Table 1.

Breast Cancer Screening Methods to Consider for Eligible Patients

Screening method How sure are we? Evidence-based conclusions

Mammography and CBE in women 40 to 49 years of age

Sure

Benefits and harms are approximately equal. Physicians may discuss but not strongly encourage screening (every year, if at all)

Mammography and CBE in women 50 to 70 years of age

Sure

Encourage (every two years is acceptable)

Mammography and CBE in women older than 70 years

Unsure

Balance of benefits and harms is uncertain; physicians may discuss with women who have an interest and are in good health


CBE = clinical breast examination.

Table 1.   Breast Cancer Screening Methods to Consider for Eligible Patients

View Table

Table 1.

Breast Cancer Screening Methods to Consider for Eligible Patients

Screening method How sure are we? Evidence-based conclusions

Mammography and CBE in women 40 to 49 years of age

Sure

Benefits and harms are approximately equal. Physicians may discuss but not strongly encourage screening (every year, if at all)

Mammography and CBE in women 50 to 70 years of age

Sure

Encourage (every two years is acceptable)

Mammography and CBE in women older than 70 years

Unsure

Balance of benefits and harms is uncertain; physicians may discuss with women who have an interest and are in good health


CBE = clinical breast examination.

Table 2

Issues in Breast Cancer Screening

Screening issue How sure are we? Evidence-based conclusions

Breast self-examination at any age

Sure

Not supported by the evidence; physicians should discourage or at least not actively encourage

MRI in women at usual risk

Unsure

Generally discourage

MRI in women with high- risk family history

Unsure

Offer as an option for a small percentage of women

Digital mammography

Unsure

Generally discourage


MRI = magnetic resonance imaging.

Table 2   Issues in Breast Cancer Screening

View Table

Table 2

Issues in Breast Cancer Screening

Screening issue How sure are we? Evidence-based conclusions

Breast self-examination at any age

Sure

Not supported by the evidence; physicians should discourage or at least not actively encourage

MRI in women at usual risk

Unsure

Generally discourage

MRI in women with high- risk family history

Unsure

Offer as an option for a small percentage of women

Digital mammography

Unsure

Generally discourage


MRI = magnetic resonance imaging.

These screening conclusions are a key part of the U.S. Preventive Services Task Force recommendation from 2002,11  and they form the heart of the recently published ACP recommendation. Table 1 summarizes the evidence for these conclusions and presents issues that physicians should keep in mind when considering breast cancer screening. Table 2 offers conclusions about additional screening methods. Patients may ask about these screening issues, but the conclusions are not calls for action—they are, at this stage, calls for inaction.

There is one conclusion we are relatively sure about: routinely teaching women breast self-examination is probably a waste of time. There are better things that physicians could do instead. The other three conclusions about MRI screening and digital mammography are issues to be resolved by future research.

Physicians should know the family histories of their patients. A small number of women (about 2 percent) have a high-risk family history of breast cancer. These women should be referred for genetic counseling and, perhaps, genetic screening. MRI screening may be considered for these women (even in the absence of good evidence). This is the primary message of the recent ACS recommendation, and it is consistent with a previous recommendation by the U.S. Preventive Services Task Force.12

That summarizes the “new” evidence. Remember to take a family history, and remember the screening issues in Table 1. Discuss screening with your patients. But, as we all know, it is unlikely this is the real end of the story—it is only the end for now. It is a safe prediction that another breast cancer screening upheaval will erupt.

Address correspondence to Russell Harris, MD, MPH, at rharris@med.unc.edu. Reprints are not available from the author.

The opinions and assertions contained herein are the private views of the author and are not to be construed as official or as reflecting the views of the Agency for Healthcare Research and Quality or the U.S. Preventive Services Task Force, of which Dr. Harris is a member.

REFERENCES

1. Pisano ED, Gatsonis C, Hendrick E, Yaffe M, Baum JK, Acharyya S, et al., for the Digital Mammographic Imaging Screening Trial (DMIST) Investigators Group. Diagnostic performance of digital versus film mam-mography for breast-cancer screening [Published correction appears in N Engl J Med 2006;355:1840]. N Engl J Med. 2005;353:1773–83.

2. Kriege M, Brekelmans CT, Boetes C, Besnard PE, Zonderland HM, Obdeijn IM, et al., for the Magnetic Resonance Imaging Screening Study Group. Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition. N Engl J Med. 2004;351:427–37.

3. Lehman CD, Gatsonis C, Kuhl CK, Hendrick RE, Pisano ED, Hanna L, et al., for the ACRIN Trial 6667 Investigators Group. MRI evaluation of the contralateral breast in women with recently diagnosed breast cancer. N Engl J Med. 2007;356:1295–303.

4. Qaseem A, Snow V, Sherif K, Aronson M, Weiss KB, Owens DK, for the Clinical Efficacy Assessment Subcommittee of the American College of Physicians. Screening mammography for women 40 to 49 years of age: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2007;146:511–5.

5. Saslow D, Boetes C, Burke W, Harms S, Leach MO, Lehman CD, et al., for the American Cancer Society Breast Cancer Advisory Group. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin. 2007;57:75–89.

6. Moss SM, Cuckle H, Evans A, Johns L, Waller M, Bobrow L, et al., for the Trial Management Group. Effect of mammographic screening from age 40 years on breast cancer mortality at 10 years' follow-up: a ran-domised controlled trial. Lancet. 2006;368:2053–60.

7. Brewer NT, Salz T, Lillie SE. Systematic review: the long-term effects of false-positive mammograms. Ann Intern Med. 2007;146:502–10.

8. Zackrisson S, Andersson I, Janzon L, Manjer J, Garne JP. Rate of over-diagnosis of breast cancer 15 years after end of Malmo mammographic screening trial: follow-up study. BMJ. 2006;332:689–92.

9. Elmore JG, Barton MB, Moceri VM, Polk S, Arena PJ, Fletcher SW. Ten-year risk of false positive screening mammograms and clinical breast examinations. N Engl J Med. 1998;338:1089–96.

10. Humphrey LL, Helfand M, Chan BK, Woolf SH. Breast cancer screening: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2002;137(5 pt 1)347–60.

11. U. S. Preventive Services Task Force. Screening for breast cancer: recommendations and rationale. Ann Intern Med. 2002;137(5 pt 1)344–6.

12. U. S. Preventive Services Task Force. Genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility: recommendation statement [Published correction appears in Ann Intern Med 2005;143:547]. Ann Intern Med. 2005;143:355–61.


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