Breast Cancer Overdiagnosis Risk May Be Substantial for Older Women

Older women screened for breast cancer were at a considerable risk of being overdiagnosed, according to a large retrospective cohort study.

Researchers found that an estimated 31% of breast cancers among screened women from the ages of 70 and 74 were potentially overdiagnosed, reported Ilana Richman, MD, MHS, of the Yale School of Medicine in New Haven, Connecticut, and colleagues.

Moreover, the risk of overdiagnosis grew with advancing age: For women ages 75 to 84, 47% of cases were potentially overdiagnosed; while an estimated 54% of breast cancers were potentially overdiagnosed among women 85 years and older.

When stratified by life expectancy, the estimated proportion of breast cancers overdiagnosis was 32% for screened women with a life expectancy or more than 10 years, 53% for women with a life expectancy of 6 to 10 years, and 63% among women with a life expectancy of 5 years or less.

The researchers did not find statistically significant reductions in breast cancer-specific death associated with screening in women ages 70 and older.

“Whether harms of overdiagnosis are balanced by benefits and for whom remains an important question,” wrote Richman and colleagues in the Annals of Internal Medicine. “Overdiagnosis should be explicitly considered when making screening decisions, along with considering possible benefits of screening.”

Richman and colleagues noted that in recent years there has been greater recognition that overdiagnosis — “which may be defined as detecting a cancer, often through screening, that would not have caused symptoms in a person’s lifetime” — represents an important harm from breast cancer screening.

The findings pointed to about 2% absolute risk for overdiagnosis after 15 years of screening. But whether that rate should be considered high, Richman and colleagues said, depends on several factors, including benefits.

“Given uncertainty about the relative balance of benefits and harms of screening in this population, patient preferences, including risk tolerance, comfort with uncertainty, and willingness to undergo treatment, are important for informing screening decisions,” they wrote.

In an editorial accompanying the study, Otis Brawley, MD, and Rohan Ramalingam, both of Johns Hopkins University in Baltimore, pointed out that the discussion of overdiagnosis of breast cancer is distinct from the question of whether mammography saves lives.

High-quality, routine mammography programs do save lives — at least for women in the age group evaluated in this study, and probably for women from the ages of 40 and 80 as well, they argued.

“Unfortunately, the public messaging does not put enough emphasis on ‘high-quality’ nor ‘routine mammography programs,'” they observed. “Until the advent of objective prognostic markers to identify indolent types of cancer, we (physicians and patients) should realize that a small but significant proportion of those cured of cancer do not need cure. An effective, objective test would spare these women the inconvenience of unnecessary therapy.”

Ultimately, they suggested the answer to the overdiagnosis problem is further study of cancer genomics.

“We need to move to a 21st-century definition encompassing both the biopsy and pathologic appearance as well as genomics,” the editorialists said. “The 21st-century definition of cancer will recognize that breast cancer is not one entity but many distinct diseases with potentially different patterns of behavior calling for different treatments and, sometimes, no treatment.”

For the study, Richman and colleagues compared the cumulative incidence of breast cancer among women 70 and older who continued to undergo screening in the next interval versus those who did not. Overdiagnosis was measured as the absolute difference in the cumulative incidence of breast cancer among women who were screened versus not screened at cohort entry.

Using data from the SEER-Medicare registry linked to a 5% sample of Medicare fee-for-service beneficiaries, the authors included 54,635 women (mean age 77.2 years, 88% white) in their analysis. Life expectancy was 10 years or less for 41% of the cohort, and 15% were considered frail.

Median follow-up times were 13.7 years among women ages 70 to 74 years, 10 years for women ages 75 to 84 years, and 5.7 years for women 85 years and older.

In adjusted analyses, the cumulative incidence of breast cancer for women screened and not screened was:

• 6.1 cases per 100 women (95% CI 5.7-6.4) versus 4.2 (95% CI 3.5-5.0) among those 70 to 74 years of age
• 4.9 cases per 100 women (95% CI 4.6-5.2) versus 2.6 (95% CI 2.2-3.0) among women ages 75 to 84 years
• 2.8 cases per 100 women (95% CI 2.8-3.4) versus 1.3 (95% CI 0.9-1.9) in women ≥85 years

Thus, the authors pointed out the absolute risk difference between groups was “similar” across age groups, ranging from 1.5 to 2.3 cases per women screened.

“The higher proportion of overdiagnosed cases among older women reflects the fact that although the absolute risk is similar across age groups, the cumulative incidence of breast cancer is lower among older women who have greater competing mortality,” they wrote.