November 28, 2008
Some Breast Cancer Cases Spontaneously Regress?

Women who are tested less for breast cancer get diagnosed less with breast cancer.

Breast cancer rates increased significantly in four Norwegian counties after women there began undergoing mammography every two years, according to a report in the November 24 issue of Archives of Internal Medicine, one of the JAMA/Archives journals. Rates among regularly screened women remained higher than rates among women of the same age who were screened only once after six years, suggesting that some of the cancers detected by mammography may have spontaneously regressed had they not been discovered and treated.

The idea here is that if the women who were tested less often really had as much lasting breast cancer as that found in the more frequently tested group then the former group really should have had more breast cancer cases found when they were finally tested . But they did not show those "missing" breast cancer occurrences at the end of the trial.

Throughout Europe, the start of screening mammography programs has been associated with increased incidence of breast cancer, according to background information in the article. "If all of these newly detected cancers were destined to progress and become clinically evident as women age, a fall in incidence among older women should soon follow," the authors write. "The fact that this decrease is not evident raises the question: What is the natural history of these additional screen-detected cancers?"

Per-Henrik Zahl, M.D., Ph.D., of the Norwegian Institute of Public Health, Oslo, and colleagues examined breast cancer rates among 119,472 women age 50 to 64 who were all invited to participate in three rounds of screening mammograms between 1996 and 2001 as part of the Norwegian Breast Cancer Screening Program. They compared these to rates among a control group of 109,784 women age 50 to 64 in 1992, who would have been invited for screening if the program had existed at that time. Cancers were tracked for six years using a national registry, and at the end of that time all participants were invited to undergo a one-time screening to assess breast cancer prevalence.

As anticipated, breast cancer rates were higher among screened women than among the control group before the final prevalence screening. "Even after prevalence screening in controls, however, the cumulative incidence of invasive breast cancer remained 22 percent higher in the screened group," the authors write. Of every 100,000 screened women, 1,909 had breast cancer during the six-year period, compared with 1,564 of every 100,000 in the control group. Screened women were more likely to have breast cancer at every age.

An alternative explanation is that each test for breast cancer has false negatives and some of these women who are tested less often are having their breast cancer getting missed. Is that possible?

Suppose this finding holds up. It has some obvious implications. First off, some of the reported claimed progress in curing breast cancer might be a mirage. More frequent testing is turning up earlier stage breast cancer. Some of that earlier stage breast cancer might disappear naturally (perhaps via an immune response) if left alone. Treatment might even impair the immune system and leave it less able to defeat the breast cancer on its own.

This report suggests some women are going thru surgery, chemo, and radiation who would otherwise recover from breast cancer without ever knowing they even had it. Given the ravages of the treatments this is quite unfortunate. But perhaps scientists can discover characteristics of cancers or of patient immune systems that make regression more likely. Then those conditions could be induced in women with breast cancer in order to cause more regressions.

We can expect great advances in early detection. Microfluidic devices will test blood samples with great sensitivity and detect blood markers for cancer (and other diseases as well). The tests will become so sensitive that we are going to hit a problem: we have lots of very small cancers in our bodies (really) that are stuck at the stage of being unable to grow more blood vessels. These very small cancers are going to contribute to a sort of background noise of cancer signals. I expect as the blood assay tests become more sensitive to very low concentrations of cancer markers we will even find that as we age a gradual slow rise in cancer blood markers will be found.

On the bright side, the ability to detect very early stage cancer will lend itself to immune treatments against cancer. Caught early enough a cancer won't have as many mutations that protect it from an immune response. In particular, I'm hopeful that vaccines and monoclonal antibodies will be developed that will rid of cancers without our even having to know the exact location of each cancer. Perhaps as we age we will periodically go in for an anti-cancer immunotherapy that basically kills any early stage cancer cells that have grown up since a previous treatment.

Share |      Randall Parker, 2008 November 28 11:13 PM  Aging Cancer Studies

rsilvetz said at November 30, 2008 11:16 PM:

One insight that is routinely missed on immunotherapies: When we finally have a successful immunotherapy for cancer, staging will be irrelevant. Once the immune system can be taught to eradicate cancer the burden of tumor mass is irrelevant -- it will be eradicated regardless of size. Supportive measures might be needed in patients where the burden is greater than 500g to avoid lytic syndromes and kidney issues, but beyond that, tumor burden will mean nothing, so whether diagnosed early or late won't matter either.

Mike said at December 1, 2008 10:47 AM:

Err... there's also another interpretation of the data. It's possible that the mammography techniques themselves contribute to causing breast cancer.

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