Kopans: JAMA Oncology paper misinterprets DCIS data

By Dr. Daniel Kopans, AuntMinnie.com contributing writer

August 24, 2015 -- Just how deadly is ductal carcinoma in situ (DCIS)? A paper by Narod et al1 published on August 20 in JAMA Oncology -- and an editorial accompanying it by Dr. Laura Esserman -- suggests that the best way to deal with DCIS is simply to ignore it, rather than treating it aggressively. But such conclusions represent a dangerous misinterpretation of the actual data on DCIS.

There are numerous fundamentally important problems with the Narod paper. In addition, although the Esserman analysis only suggests that the results are the same regardless of the therapy used to treat DCIS, the paper has been reported by some of the media as if DCIS was innocuous and "overtreated."

The paper actually shows that even though the risk of dying from DCIS is less than for invasive lesions (which we have known for decades), the death rate of women with DCIS is higher than for women who do not have DCIS. This has been misreported as saying that women with DCIS do not die at a higher rate, when the paper suggests that the rate of death for women treated for DCIS is almost twice that of the population.

Dr. Daniel Kopans
Dr. Daniel Kopans from Massachusetts General Hospital.

The authors state that the importance of the paper is as follows: "Women with ductal carcinoma in situ (DCIS), or stage 0 breast cancer, often experience a second primary breast cancer (DCIS or invasive), and some ultimately die of breast cancer."

The paper has also been misinterpreted as suggesting that women with DCIS do not need any treatment. We still have no idea which DCIS lesions, if left alone, will progress to become invasive and become lethal. All the patients in this analysis were treated, so no one can make any legitimate claim that there is no need for treatment.

The Esserman analysis suggests that they could not find any difference in survival between the various forms of therapy, which is not surprising. Most treatment to the breast for breast cancer (nonsystemic) is undertaken to prevent recurrences in the breast. Most treatment of the breast has little influence (there may be some) on overall survival for any type of breast cancer.

What saves lives is early treatment (before metastatic spread has occurred) and systemic treatment to try to destroy any microscopic cancer that has made its way to other organs. Lumpectomy and radiation are, essentially, the same as mastectomy for invasive cancers, and the authors are suggesting that the same is true for DCIS.

The most important point about this paper and its suggestion that there is no need to treat DCIS is that all of the women whose records were evaluated were treated. The authors can suggest that they could not find any differences based on the method of treatment, but they cannot conclude that there is no need for some form of treatment.

There are also other issues that need to be addressed that appear to have been overlooked by any peer review.

The women appear to have had one of three therapeutic interventions. One group had a "lumpectomy" (19,762 women) without radiation, which, in the absence of patient data, was likely excision to "clear margins" and likely involved mostly small, low-grade lesions.

A second group had a lumpectomy plus radiation (42,250 women), and the third group had mastectomies (25,527 women). The women in the latter two categories likely had larger, higher-grade lesions.

The immediate concern with the data is that there was likely a great deal of selection bias associated with the choice of therapy. This was not a random allocation, so the groups are not comparable. It is almost certain that the types of lesions in the women in the three groups were not evenly distributed.

Another worrisome finding is that the numbers in the three groups only add up to 87,539, whereas the authors claim to have evaluated 108,196 women. What happened to the other 20,657? Of the total women, 20% appear not to have been included in the analysis. How were they treated and what were their results?

There are legitimate disagreements as to how to treat DCIS lesions. Every time physicians have tried to reduce the amount of treatment, cancer recurrence rates increase in the breast, and many lesions return as invasive (more dangerous) cancers, as indicated in a paper by Wong et al.2

The Wong et al paper also brings up another worrisome finding in the Narod paper. Narod et al found that the 10-year recurrence rate for women who underwent lumpectomy alone, based on national data, was only 3%. Yet Wong et al, performing lumpectomy alone with wide margins of 1 cm or more for low- and intermediate-grade (i.e., favorable) lesions, showed a recurrence rate of 4% at only five years of follow-up. There appears to be something fundamentally wrong with the Narod data.

There was a commentary in the Washington Post that also, incorrectly, stated that removing all of the DCIS over the years has not reduced the incidence of invasive breast cancer, which you would expect if DCIS is the precursor to invasive cancer. In fact, the incidence of invasive cancer has declined in the U.S.,3,4 and this is likely due to the removal of DCIS lesions over the years so that they did not progress to become invasive cancers.

References

  1. Narod SA, Iqbal J, Giannakeas V, Sopik V, Sun P. Breast cancer mortality after a diagnosis of ductal carcinoma in situ. JAMA Oncol. August 20, 2015. doi: 10.1001/jamaoncol.2015.2510.
  2. Wong JS, Kaelin CM, Troyan SL, et al. Prospective study of wide excision alone for ductal carcinoma in situ of the breast. J Clin Oncol. 2006;24(7):1031-1036.
  3. Kopans DB. Arguments against mammography screening continue to be based on faulty science. Oncologist. 2014;19(2):107-112.
  4. Helvie MA, Chang JT, Hendrick RE, Banerjee M. Reduction in late-stage breast cancer incidence in the mammography era: Implications for overdiagnosis of invasive cancer. Cancer. 2014;120(17):2649-2656.

Dr. Kopans is a professor of radiology at Harvard Medical School and a senior radiologist in the department of radiology, breast imaging division, at Massachusetts General Hospital.

The comments and observations expressed herein are those of the author and do not necessarily reflect the opinions of AuntMinnie.com.


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