More on Mammogram Over-Diagnosis

Surgeon/scientist Orac has written a wonderful in-depth analysis of Bayer and Welch’s recent NEJM article on 30 years of mammography screening. I strongly recommend you read Orac’s post, entitled “Cracks  Spin vs Science on Mammography”,  if you are interested in exploring this topic further.

The post, like most of what Orac writes, is incredibly informative but very long (I thought I was verbose, but he beats me every time), so allow me to summarize the points I took home from reading it –

• The NEJM study’s finding of over-diagnosis is in line with prior studies, strengthening it as a real possibility, but does not excluding the possibility that both studies have as yet unidentified biases that lead to the finding of over-diagnosis.

• The study used SEER data, which is not perfect, and made some assumptions that could have over-estimated the rate of over-diagnosis, again not perfect and possibly over-estimating, but not eliminating, mammogram’s rate of over-diagnosis.
• Using the rates of breast cancer in women under 40 as a surrogate for breast cancer mortality rates in un-screened women over age 40 may not be appropriate, as the biology of breast cancers in younger women is likely to be very different than those in women over 40. Unfortunately, there is not a better comparison group that could have been used instead.
• The study ignores the possibility that stage creep could account for the lack of decline in later stage breast cancers of time. This is a phenomenon  in which previously so-called early cancers are more likely now to be classified as later stage due to better detection of tumor cells in axillary nodes using sentinal node biopsy. This is a concept of which I had not been aware.

One study suggested that the stage migration rate was as high as one in four; i.e., 40% of patients having “positive” axillary lymph nodes with SLN biopsy compared to 30% having positive nodes using axillary dissection. Another studyreported similar results. How this would affect Welch’s analysis is hard to tell, and correcting for it is probably not possible using the SEER database, particularly given that the extent of “up-staging” is not fully known yet. Be that as it may, an increase in the apparent incidence of patients with positive lymph nodes would increase the apparent incidence of advanced disease and decrease any decline in the incidence of advanced disease. How large this effect is, I don’t know, but it would suggest that the rate of over-diagnosis is lower than what Welch estimates. How much lower, or whether stage migration is even a significant factor, I don’t know, but I wish that Welch had at least mentioned it.

• Could mammogram be victim of the so-called  “the decline effect”?

Basically, this is a term for a phenomenon in which initial results from experiments or studies of a scientific question are highly impressive, but, over time, become less so as the same investigators and other investigators try to replicate the results, usually as a means of building on them.

Orac also takes on the extremists on both sides of the issue – those that would use the study as fodder to paint mammograms as evil – or as he puts it,  “The cranks have had a chance to discover the study” – as well as those in the medical profession who refuse to accept any criticism of mammography – one actually calling it “malicious nonsense”.

…the Bleyer and Welch study is simply more evidence that the balance of risks and harms from mammography is far more complex than perhaps we have appreciated before. It’s very hard for people, even physicians, to accept that not all cancers need to be treated, and the simplicity of messaging needed to promote a public health initiative like mammography can sometimes lead advocacy groups astray from a strictly scientific standpoint.

It has weaknesses and might well overestimate the rate of overdiagnosis, but overdiagnosis is a real phenomenon….As I said, it’s hard for many physicians to accept that not all cancer necessarily needs treatment. Certainly this is likely to be true for ductal carcinoma in situ (DCIS), which consists of cancerous cells that have not yet invaded through the basement membrane of the ducts. Unfortunately, this is the predominant form of breast cancer that is detected by mammography.  Indeed, the authors even point out that their method didn’t allow them to disentangle the incidence of DCIS from that of invasive breast cancer, thanks to the way that the SEER database is setup. The problem, of course, is that we don’t know how to predict which cancers will progress and which cancers will not.

Finally, for all the confusion this study causes, there is one spot of good news, and that’s the observation that much of the decline in breast cancer mortality over the last 20 years—yes, contrary to what you might have heard, breast cancer mortality has actually been steadily decreasing—is likely due to improvements in treatment.

Finally, he reminds us that, for all its limitations, mammograms are not going anywhere anytime soon.

…right now reports of the death of mammography are very premature. To me, what is most important in breast cancer screening right now is to develop reliable predictive tests that tell us which mammographically detected breast cancers an be safely observed and which ones are likely to threaten women’s lives. We are currently at a point where imaging technology has outpaced our understanding of breast cancer biology, or, as Dr. Welch put it, “Our ability to detect things is far ahead of our wisdom of knowing what they really mean.” Until our understanding of biology catches up, the dilemma of overdiagnosis will continue to complicate decisions based on breast cancer screening.

Thanks, Orac. I always learn from reading your posts.