Nick Mulcahy

July 14, 2009 — One in 3 breast cancers detected in publicly organized screening programs is overdiagnosed. And overtreatment inevitably occurs at the same rate, according to a meta-analysis of screening programs in Canada, Australia, Norway, Sweden, and the United Kingdom, published online July 9 in BMJ.

The new analysis is yet another study that adds to the controversy surrounding mammography's benefits and harms, which include overdiagnosis and overtreatment.

"The question is no longer whether overdiagnosis occurs, but how often it occurs," writes Gilbert Welch, MD, in an editorial accompanying the newly published analysis.

Overdiagnosis of cancer refers to cancers that grow so slowly that the patient dies of other causes before it produces symptoms or to cancer that is dormant or even regresses, explained Dr. Welch, who is a professor of medicine at Dartmouth Medical School in Hanover, New Hampshire.

Overdiagnosis is a "widely recognized problem" in prostate cancer screening, said Dr. Welch.

With regard to breast cancer, there is a growing body of evidence about overdiagnosis with which the new study is consistent, he added.

Namely, there are now 5 observational studies that indicate screening mammography is associated with increases in the incidence of breast cancer in women of screening age, but that there is "little or no subsequent decrease in the incidence of older women," notes Dr. Welch.

But is the rate of overdiagnosis really as high as 1 in 3 screen-detected cancers?

Dr. Welch says that that the "most compelling evidence to date" about overdiagnosis comes from an earlier randomized controlled trial of mammography versus observation (BMJ. 2006;332:689-692). In that study, overdiagnosis from screening occurred at a rate of 1 in 6, Dr. Welch notes.

Whatever the rate of overdiagnosis, both the study authors and the editorialist agree, overtreatment is likely to occur at the same rate.

"As it is not possible to distinguish between lethal and harmless cancers, all detected cancers are treated," write the study authors, Karsten Juhl Jørgensen, MD, and Peter C Gøtzsche, MD, from the Nordic Cochrane Center in Copenhagen, Denmark.

Close Call

The balance between the benefits and harms of mammography make it one of medicine's "close calls," adds Dr. Welch. It is a close call that has received a lot of public attention in the past year.

In the United Kingdom, there was public outcry over the lack of information about the harms of mammography in a public-health pamphlet about breast cancer screening. The protest led to a rewrite of the pamphlet, as reported by Medscape Oncology.

Furthermore, The New York Times and other media made front-page news out of a 2008 study from Norway that concluded that about 20% of screen-detected invasive breast cancers spontaneously regress. One of the Norwegian researchers told Medscape Oncology that such lesions are "pseudo-cancers."

In making decisions about whether or not to get screened, women are probably most interested in the "trade-off between the number of deaths from breast cancer avoided and the number of cancers overdiagnosed," suggested Dr. Welsh.

In an effort to provide physicians and their patients with a "balance sheet" of the harms and benefits of mammography, Dr. Welch included a tabular display along with his editorial. The credits and debits are for every 1000 women undergoing annual mammography for 10 years starting at the age of 50 years.

New Study Details

To estimate the extent of overdiagnosis in organized screening programs, the Danish investigators compared trends in breast cancer incidence before and after the screening was initiated in the United Kingdom; Manitoba, Canada; New South Wales, Australia; Sweden; and parts of Norway.

The reason for this approach is based on the idea that, if screening was effective and did not produce overdiagnosis, then "the initial increase in cancers in the screened age groups would be fully compensated for by a similar decrease in the older age groups no longer offered screening," write the authors. Why is this so? Because the cancers in the older age groups would have been detected earlier on in life, as a result of screening, explain the authors.

The authors also note that such an approach must take into account changes in the background incidence of breast cancer and other factors.

One set of data offers an example of how the analysis was conducted. In Sweden, nationwide screening began in 1986, and in 1998, "almost all eligible women had been offered screening," the authors write. In 2000, the increase in invasive cancer after screening was implemented was 54% above expected rates for women aged 50 to 59 years and 21% for women aged 60 to 69 years. A drop in the incidence of breast cancer occurred among women aged 70 to 84 years, but the incidence "approached the expected rate," write the authors. In short, 88% of the increase among younger women was not compensated for by any drop in the older women, note the authors.

In summary, the total overdiagnosis of breast cancers, including ductal carcinoma in situ, from these public screening programs in different countries was 52%. The overdiagnosis of invasive breast cancer was 35%, report the authors.

The authors have disclosed no relevant financial relationships.

BMJ. 2009;339:b1425 and b2587. Abstract, Abstract