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 a consultant for and receives grant/research support from HRA Pharma, Bayer Healthcare, Merck, Agile Pharm, Population Council, AbbVie, Evofem, and ContraMed; and is a consultant for Teva Pharmaceuticals and MicroChips.

Synopsis: A new study reports that in the United States, the incidence of breast cancer is higher in counties with high rates of mammography screening, but screening is not associated with a decrease in breast cancer deaths. The decision of whether and how often to perform mammography requires a discussion of the potential consequences of both true positive and false positive screening tests.

Source: Harding C, et al. Breast cancer screening, incidence, and mortality across U.S. counties. JAMA Intern Med 2015; Jul 6. doi: 10.1001/jamainternmed.2015.3043. [Epub ahead of print].

A new study by Harding et al in JAMA Internal Medicine took advantage of the natural variation in screening mammography rates across the United States to investigate the associations of screening with breast cancer incidence, tumor size, and mortality using an ecological study design.1 The study population was 16 million women 40 years of age or older who resided in 547 counties reporting to the Surveillance, Epidemiology, and End Results cancer registries during the year 2000. During that year 53,207 women within this population were diagnosed with breast cancer, and 10-year follow-up was available for 95%. The study exposure was the percentage of women who had a mammogram in the past 2 years in each county as published by the National Cancer Institute’s Small Area Estimates for Screening Behaviors program. The main outcome measure was the breast cancer incidence in 2000 and incidence-based breast cancer mortality during the 10-year follow-up. The incidence and mortality calculated for each county were adjusted for age to the U.S. population. The size of the tumor was also correlated to mammogram exposure in the population.

Although a positive correlation was found across these U.S. counties, between the extent of mammogram screening and breast cancer incidence (weighted r = 0.54; P < 0.001), there was no correlation between screening and breast cancer mortality over the 10 years of follow-up (weighted r = 0.00; P = 0.98). Looking across all counties, an absolute increase of 10 percentage points in the extent of screening was accompanied by 16% more breast cancer diagnoses (relative risk [RR], 1.16; 95% confidence interval [CI], 1.13-1.19) but no significant reduction in breast cancer deaths (RR, 1.01; CI, 0.96-1.06). An increase of 10 percentage points in screening rates was also associated with a significant increase in the incidence of both small (< 2 cm; RR, 1.25; CI, 1.18-1.32) and large (RR, 1.07; CI, 1.02-1.12) breast cancers, but the effect for large tumors was not clinically important. Put another way, screening increased the detection of small tumors but not large tumors. The authors concluded that these findings — an increase in the diagnosis of additional small cancers with no concomitant decline in the detection of larger cancers or breast cancer mortality — support the conclusion that screening mammography leads to widespread overdiagnosis.

I have previously discussed the results from several studies2,3 that support the conclusions of Harding et al that mammography results in widespread overdiagnosis of breast cancer. Overdiagnosis is a true positive result of screening that fails to result in a net benefit to the patient. In the case of breast cancer overdiagnosis, the possibility of harm is real when one considers mastectomy, chemotherapy, and out-of-pocket treatment costs. This is in addition to the false-positive screens that result in additional unnecessary worry and follow-up interventions.4 However, a companion commentary by Joann Elmore published in the same issue of JAMA Internal Medicine eloquently states the clinical conundrum: “Women will increasingly approach their physicians with questions and concerns about overdiagnosis, and we have no clear answers to provide. We do not know the actual percentage of overdiagnosed cases among women screened, and we are not able to identify which women with newly diagnosed DCIS or invasive cancer are over-diagnosed. Many screening guidelines now mandate shared and informed decision making in the patient-physician relationship, but this is not an easy task.”5

Since it is not possible for us to determine which early breast cancers will behave in an indolent fashion and which will be aggressive, the decision to screen must be personal. This requires a different type of counseling than most women receive. Consider whether your own discussions reflect this controversy. The commentary by Elmore cited three studies that should influence the discussions you have with patients tomorrow. First, while most women (96.3%) report that their healthcare providers discussed the benefits of screening mammography, few (19.5%) mention that their provider discussed potential harms such as overdiagnosis.6 In the second study, the investigators conducted focus groups of Australian women to explore how awareness of overdiagnosis might influence attitudes and intentions about screening mammography.7 While subjects overwhelmingly reacted to information about overdiagnosis with surprise, the effects on attitudes to screening varied. About half remained committed to screening despite the problems associated with overdiagnosis, while others would give further thought to the screening decision or to a treatment decision if a screen was positive. Regardless of the decision, most participants felt that receiving information regarding overdiagnosis was important in order to make an informed choice. Of interest, some subjects expressed suspicion that overdiagnosis research was actually a government plot to cut funding for mammography screening! The authors of this qualitative study then went on to complete a randomized clinical trial that evaluated the effects of a decision aid providing information about the concept and frequency of overdiagnosis.8 They found that compared to controls who did not use the decision aid, users of the aid reported a significant increase in overall knowledge (29% vs 17%; P < 0.0001), with fewer users expressing positive attitudes toward screening (69% vs 83%; P < 0.0001) and intention to be screened (74% vs 87%; P < 0.0001).

Taken together, these studies suggest that giving women more information will help them come to the best decision. Many will chose to continue annual screening. Some will choose a less frequent interval or will avoid mammography screening altogether. You don’t need a decision aid; you just need to take a little extra time in counseling for this important decision. Although this takes a formally routine conversation to a different level of uncertainty, your patients will appreciate the honest and extra attention.

As was true in the qualitative study, I find most patients in my practice regard the limitations of mammography surprising and somewhat disappointing. Although both true positives (overdiagnosis) and false positives from mammography can result in real harm, a better alternative does not exist. The U.S. Preventive Services Task Force (USPSTF) recommends against routine screening mammography in women age 40-49 years, concluding that the risk of harm attributable to screening exceeds the potential benefit for low-risk women.4 Mammography for women age 50-74 years is recommended, but only every 2 years, and the USPSTF concluded that the evidence of additional benefits and harms of screening mammography in women 75 years or older was inconclusive. Based on all this information, some of my patients have decided to reduce the interval of screening mammograms and a few have discontinued screening. More than half accept these limitations and continue with annual screening. Providing information and choice allows a woman to make the best decision for herself.

References

  1. Harding C, et al. Breast cancer screening, incidence, and mortality across U.S. counties. JAMA Intern Med 2015; Jul 6. doi: 10.1001/jamainternmed.2015.3043. [Epub ahead of print].
  2. Bleyer A, Welch HG. Effect of three decades of screening mammography on breast-cancer incidence. N Engl J Med 2012;367:1998-2005.
  3. Miller AB, et al. Twenty-five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: Randomised screening trial. BMJ 2014;348:g366.
  4. Force USPST. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2009;151:716-26, W-236.
  5. Elmore JG, Etzioni R. Effect of screening mammography on cancer incidence and mortality. JAMA Intern Med 2015; Jul 6. doi: 10.1001/jamainternmed.2015.3056. [Epub ahead of print].
  6. Hoffman RM, et al. Decision-making processes for breast, colorectal, and prostate cancer screening: The DECISIONS survey. Med Decis Making. 2010;30(5 Suppl):53S-64S.
  7. Hersch J, et al. Women’s views on overdiagnosis in breast cancer screening: A qualitative study. BMJ 2013; Jan 23. 346:f158. doi: 10.1136/bmj.f158.
  8. Hersch J, et al. Use of a decision aid including information on overdetection to support informed choice about breast cancer screening: A randomised controlled trial. Lancet 2015;385:1642-1652.