The study, published Monday in the journal Archives of Internal Medicine, suggested breast cancer screening may be leading to overdiagnosis of cancer, with upwards of 22 percent of cases likely to resolve themselves without treatment.
Once a breast cancer is found, however, it wouldn't currently be considered ethical not to treat. So - if the theory is correct - large numbers of women may be having surgeries, radiation, chemotherapy and other treatments that would never have been needed if their cancers hadn't been detected.
"If we are right, then this is a kind of paradigm shift," said lead author Dr. Per-Henrik Zahl, a senior statistician with the Norwegian Institute of Public Health.
Zahl, who admitted he has been trying to get the study published for about four years, said the risks of over diagnosis of breast cancer are real.
Radiation can do significant and permanent damage to the heart and coronary arteries. Chemotherapy can cause cognitive confusion. And surgery that involves the removal of lymph nodes can cause lymphedema, the painful swelling of the arm closest to the involved breast.
Dr. Patrick Remington has been studying the idea of self-limiting breast cancers since the early 1990s, when the introduction of breast screening programs showed a sharp and sustained increase in the incidence of the disease in the United States. He is convinced some invasive breast cancers do regress; they have become known as LMPs or cancers of "limited malignant potential."
"I would say a very good guess would be about one out of three women have cancers detected today that would not have progressed otherwise," said Remington, a professor of population health sciences at the University of Wisconsin. Remington was not involved in this study.
He notes some other types of cancers - prostate and recently lung - have been shown to spontaneously regress in some patients.
In the case of prostate cancer, some physicians urge an approach known as watchful waiting, where patients are monitored to see if their disease is progressing; only then is it treated. That approach is not currently an option with breast cancer.
"The hope is that we'll get more research to find out if breast cancer can regress on its own," said CBS' The Early Show contributor Dr. Holly Phillips.
Zahl's findings are likely to spark heated debate. In fact, he acknowledged several journals refused to publish the study before it was accepted by Archives of Internal Medicine, a journal published by the American Medical Association.
But an editorial in the journal stressed that the findings are consistent with several observations about breast cancer that have troubled investigators for years.
And the editorial's authors, Dr. Robert Kaplan of the UCLA School of Public Health and Dr. Franz Porzsolt of Germany's Clinical Economics University of Ulm, said the hypothesis of breast cancer regression, while counterintuitive, is "difficult to rule out."
"We know from autopsy studies that a significant number of women die (from other causes) without knowing that they had breast cancer," they noted.
Dr. Steven Narod, a leading breast cancer researcher at Toronto's Sunnybrook Health Sciences Centre, agreed the findings are persuasive.
"I do agree with them that the best explanation of the findings is that about 10 to 20 per cent of the breast cancers . . . disappeared on their own," he said.
"I'm still a bit skeptical and there's alternative explanations, but I think this one is worth paying attention to."
In what Narod described as an "elegant" study design, Zahl and his colleagues used the introduction of a breast cancer screening program in Norway to explore the question.
They compared breast cancer rates among nearly 120,000 women who had three rounds of mammography between 1996 and 2001 to those among nearly 110,000 women of the same age range (50 to 64) in the five-year period preceding the start of the breast cancer screening program. Those women, known as the controls, had one mammogram.
In statistical terms, the two groups of women were identical. Their educational profile was closely matched, they had roughly the same average family income and the same average number of children. So the rates of cancers in the two groups should have been equal.
In fact, the women who hadn't been regularly screened had 22 percent fewer breast cancers.
The authors explore a number of arguments about why that might be. They noted for instance that use of hormone replacement therapy in the part of Norway where the women lived increased substantially between 1996 and 2001, the period when the screened women were undergoing regular mammograms. HRT use is linked to increased risk of breast cancer.
Women who opt to get regular mammograms may also do so because they have a higher risk of breast cancer, because of their family history, says Phillips.
But the authors conclude none of the potential other explanations could account for such a large difference between the two groups.
"All the caveats that could be explored have been explored in terms of accounting for the things that people would call ... weaknesses" of the study, agreed Dr. Cornelia Baines, a professor in the University of Toronto's school of public health and co-principal investigator of a landmark study into mammography, the Canadian National Breast Screening Study.
Baines, who has been diagnosed with breast cancer which was earlier missed in a mammogram, said the findings are important.
But she added that even if Zahl and his co-authors are correct, there's no way currently to put the findings into application.
"The incontrovertible truth is that once you've screened a woman and you find an abnormality, you have to biopsy," she said.
"If you biopsy, you have to follow through with surgery if the biopsy reveals malignant tissue. You can't stop that. You can't say: `Well, I've been screened and there is a chance that this is over diagnosis.' You can't do that."
Finding ways to answer the questions raised by the study will be difficult, experts said. And Remington noted even if doctors could differentiate, women and-or their health-care professionals might still opt for treatment to play it safe.
He suggested, though, studying women whose cancers regress on their own could teach scientists how to trigger the same response in women whose cancers aren't self-limiting, and maybe even to prevent breast cancer from developing.
And in the meantime, Baines said, this study may serve as an important reminder to women and the medical community.
"What is important and it seems to me it's been ignored for a long, long time is that ... screening doesn't only have upsides. It has downsides," she said.
"And if women want to accept the downsides and proceed with screening, then that's great. But I personally believe that they should only make that choice when they are fully informed. And a lot of them have not been fully informed about the over diagnosis scenario."