Margin Width the Key to Control of Ductal Carcinoma In Situ of the Breast
Atlanta, May 15, 1999 -- Patients with one of the most common and curable forms of breast cancer may be undergoing radiation therapy unnecessarily, according to study findings revealed at the 1999 American Society of Clinical Oncology (ASCO) meeting by Melvin J. Silverstein, MD, medical directory of the Harold E. and Henrietta C. Lee Breast Center at the USC/Norris Comprehensive Cancer Center.
Silverstein, a surgical oncologist, and colleagues examined ductal carcinoma in situ (DCIS), a noninvasive breast cancer that has been the subject of a recent heated debate over treatment. Until 1980, DCIS was a relatively uncommon disease, representing only about 1 percent of all newly diagnosed cases of breast cancer. During the past two decades -- as mammography has become more widely used and technically better -- the number of new cases has increased dramatically.
Today DCIS represents as much as 40 percent of new breast cancer cases diagnosed by mammography, and estimates suggest that approximately 40,000 new cases of DCIS will be diagnosed this year in the U.S. Seventy to 80 percent of these patients are eligible for breast preserving lumpectomy rather than mastectomy. But opinion is currently divided on whether radiation therapy is necessary for all DCIS patients who choose lumpectomy.
Silverstein et al 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.
"Wide margin width makes complete excision more likely," says Silverstein. "Since DCIS is a noninvasive cancer that does not spread (metastasize), complete excision should cure the patient. These findings will have important ramifications for thousands of women with the disease. These data suggest that radiation therapy may not be the best option for some subgroups of patients with DCIS who choose to preserve their breast."
Treatment failure after breast conservation for DCIS was measured by local recurrence of noninvasive disease or progression to invasive breast cancer. Using a Cox regression analysis with backward elimination, the researchers looked at 10 factors which might contribute to local recurrence: age, tumor size, margin width, histologic and biologic classification, nuclear grade, necrosis, HER2 overexpression, p53 mutation, and palpability.
These data, the result of an analysis of 480 nonrandomized patients choosing breast preservation, suggest that eradication of the cancer can be achieved when margin widths are sufficiently wide. For the purposes of the study tumors were divided into three groups by margin width (determined by direct measurement or ocular micrometry); close or involved (less than 1 mm); intermediate (1 to less than 10 mm) and wide (10 mm or more).
"The fact that there were only three recurrences among 138 patients with 10 mm or greater margins makes it unlikely that radiation therapy could have any significant impact on this subgroup," says 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 the intermediate margin width subgroup (1 to less than 10 mm) there was an 8 percent reduction in local recurrence rate when postoperative radiation therapy was used, but the trend was not statistically significant, according to Silverstein. In patients with margin widths less than 1 mm, there was a statistically significant 27% reduction in local recurrence.
Part of the controversy over treatment for DCIS stems from the fact that to date only one prospective randomized 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 with DCIS who elect to preserve their breast. This is a recommendation that Dr. Silverstein and colleagues on the study consider it too broad at this time. "It is like treating every patient with an infection with antibiotics -- it simply isn't necessary," says Silverstein.
"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 and discriminating 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."
According to Silverstein, radiotherapy is expensive (at times in excess of $15,000) and, in some cases, is accompanied by 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 followup more difficult, and may result in delayed diagnosis if there is a recurrence. Additionally, radiation therapy makes skin-sparing mastectomy more difficult or sometimes impossible, 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 small or nonexistent benefits are not worth the drawbacks and urges all patients with DCIS considering radiation therapy to seek a second opinion.
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. At USC we use multiple guide wires in surgeries to localize all DCIS lesions followed by complete and sequential tissue processing," 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."
"The balance between adequate margins and a good cosmetic result is a difficult one to achieve," says Silverstein. "Although most of these technologies are available in the community they are not often well integrated. For now, the best treatment options lie with specialized multidisciplinary breast centers. They have all the resources -- in terms of skilled radiologists, surgeons, and pathologists, working as an integrated team."
"The current paradigm requires radiation therapy for all patients 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."