For many women diagnosed with breast cancer, the well-publicized side effects of radiation and chemotherapy treatments inspire dread so deep that they are almost as feared as cancer itself. And although radiation therapy is generally recommended after lumpectomy, patients with one of the most common and curable forms of breast cancer may be undergoing radiation therapy unnecessarily, according to a USC study to be published in the May 13 New England Journal of Medicine (NEJM).
The study examines ductal carcinoma in situ (DCIS), a noninvasive breast cancer. Its treatment has been the subject of heated debate. Until recently, DCIS was a relatively uncommon disease, representing only about 1 percent of all newly diagnosed cases of breast cancer.
During the past decade, as mammography has become more widely used and technically improved, the number of new cases has increased dramatically.
Today DCIS represents as much as 40 percent of cases diagnosed by mammography, and estimates suggest that approximately 40,000 new cases of DCIS will be diagnosed this year in the U.S. Close to 70 percent of these patients opt for breast preserving lumpectomy over mastectomy. But opinion is currently divided on whether radiation therapy is necessary for all DCIS patients who choose lumpectomy.
In the NEJM article, Melvin J. Silverstein, M.D., medical director of the Harold E. and Henrietta C. Lee Breast Center at the USC/Norris Hospital, and colleagues found that radiation therapy does not appear to benefit patients where the margin width – the distance between the boundary of the lesion and the edge of the excised specimen – is 10 millimeters or more.
“These findings will have important ramifications for thousands of women with the disease,” says Silverstein. “The data suggest that radiation therapy may not be the best option for some subgroups of patients with DCIS who choose to preserve their breast.”
The USC data, the result of an analysis of 469 patients choosing breast preservation, suggest that eradication of the cancer can be achieved when margin widths are sufficient.
“The fact that there were only three recurrences among 133 patients with 10 mm or greater margins makes it unlikely that radiation therapy could have any significant impact on this subgroup,” said Silverstein.
When the margin widths are less than 10 mm, radiation therapy should remain a treatment option. The benefit of radiation therapy increases as the margin width decreases – so that patients in whom the margin width is less than 1 mm show the most significant benefit from postoperative radiation therapy. In fact, there is a 40 percent recurrence for the smallest margins – even with radiation.
Part of the controversy over treatment for DCIS stems from the fact that only one major study has been published. This is protocol B-17, conducted by the National Surgical Adjuvant Breast & Bowel Project (NSABP), which strongly advocates excision plus radiation therapy for all patients who elect to preserve their breast. This is a recommendation that Silverstein and colleagues on the study consider too broad at this time.
“In defense of the NSABP, its trial was designed more than 14 years ago,” says Silverstein. “At that time researchers were asking a single broad question: Does radiation therapy benefit patients with ductal carcinoma in situ treated with breast preservation? The answer to that question is clearly, yes. However, the NSABP study was not designed to answer the more sophisticated questions we ask today of exactly which subgroups might benefit from radiotherapy and by how much. If the benefit in a given subgroup is small, the advantage gained by radiation therapy will probably be more than offset by its cost and side effects.”
Silverstein said radiotherapy is costly (often in excess of $15,000) and, in a very few cases, is accompanied by occasional side effects. Radiation fibrosis is the most common side effect, particularly with some of the older outmoded radiotherapy techniques common during the 1980s.
This complication changes the texture of the breast, makes mammographic follow-up more difficult, and may result in delayed diagnosis if there is a recurrence. Moreover, radiation therapy makes skin-sparing mastectomy more difficult, if required later. Doctors must weigh the benefits of radiation therapy, in terms of decrease in local recurrence, against the side effects, complications, inconvenience, and costs of radiation therapy. Silverstein argues that for many women the benefits are not worth the drawbacks.
In an attempt to achieve sufficiently wide margins, closely integrated teamwork is key says Silverstein. To achieve this, breast cancer surgery is best performed by an integrated, experienced team of surgeon, pathologist and radiologist – with long-term follow-up by a team consisting of radiologist, surgical and medical oncologist.
More than 90 percent of DCIS is found by mammography. It’s neither palpable nor visible in the operating room. In other words, the surgeon can’t feel it or see it. “The initial excision offers the best chance to remove the cancer with adequate margins while achieving the best possible cosmetic result. That’s why pathology beyond the normal scope is also crucial. At USC we use multiple guide wires in surgeries to localize all DCIS lesions,” says Silverstein. “It’s very difficult to remove a DCIS and achieve an adequate margin using a single wire, which is the current standard throughout the U.S.”
“Surgeons walk a thin line when they attempt to completely remove a DCIS. The balance between adequate margins and a reasonable cosmetic look is a difficult one to balance,” said Silverstein. “Community breast oncologists have access to these surgical methods. For now, the best treatment option lies with specialty breast centers. I urge patients considering radiation therapy for DCIS to seek a second opinion”
“The current state of the art requires radiation therapy for all with DCIS who elect breast preservation,” concludes Silverstein. “This paper may change such thinking – in that it allows clinicians to identify patients for whom there will be little or no benefit from radiation therapy.”