Management of diagnoses such as ductal carcinoma in situ is todays breast cancer battleground, Bernard Fisher, M.D., scientific director of the National Surgical Adjuvant Breast and Bowel Project, told an audience at the 22nd Annual San Antonio Breast Cancer Symposium.
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The real question is, "Should DCIS be treated as cancer or just by excision and observation?" asked Monica Morrow, M.D., director of the Lynn Sage Comprehensive Breast Program at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago. Several studies have helped to fill the previous void in DCIS research and to answer that question, but current treatment protocols continue to lead to the possibility of recurrence in some women or overtreatment in others.
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A New Standard Treatment?
Until the past decade, mastectomy was accepted as standard treatment for DCIS, with a low recurrence rate of 1% to 2%. But studies since the 1980s have shown that the less radical approach of breast-conserving surgery together with radiation is a possible alternative for patients with DCIS.
Morrow showed the results of an 8-year follow-up of an NSABP study (NSABP B-17) that found that women with localized, mammographically detected DCIS who had lumpectomy plus radiation had a decrease in incidence of invasive carcinoma as well as a decrease in incidence of recurrence of noninvasive carcinoma compared with women who had lumpectomy alone. This led the NSABP to recommend radiation therapy as standard practice for all DCIS patients following breast-conserving surgery.
"Does this study tell us that all women with DCIS will benefit from radiation, or can we identify subsets in which radiation can be eliminated?" asked Morrow. The study found that in patients with DCIS, only the degree of comedo necrosis (the necrotic cells that fill the duct in the so-called "comedo" form of DCIS) is an important predictor for recurrence following lumpectomy.
Moderate to marked comedo necrosis was found to be a predictor of disease recurrence in both irradiated and nonirradiated patients. Larger tumor size and smaller margin width of normal tissue surrounding the excised lesion, as were previously thought, were not found to be factors that were statistically correlated with a higher risk of subsequent tumors.
In this issue of the Journal, Frederic Waldman, M.D., and colleagues from the UCSF Cancer Center looked at the links between DCIS tumors and their subsequent recurrences on a molecular level (see article, p. 313). Using a technique called comparative genomic hybridization, they analyzed DCIS tumors and recurrences from 18 women. They found a high degree of concordance in the genetic changes in 17 of 18 tumor pairs analyzed suggesting that the recurrence arose from residual disease. "We conclude that most DCIS recurrences result from growth of persistent neoplastic cells, which may remain indolent for long periods," they wrote. "These data explain the importance of wide surgical margins and/or radiation therapy during treatment of these noninvasive neoplasias."
Adding Tamoxifen
The NSABP also designed the B-24 study, which introduced tamoxifen to the lumpectomy-radiotherapy DCIS treatment protocol. The results of this study, published in the June 12, 1999, Lancet, examined whether a regimen of lumpectomy, radiation therapy, and tamoxifen was more beneficial than lumpectomy and radiation therapy alone. The rate of recurrence in this trial of the lumpectomy plus radiation group was the same rate of recurrence seen in the B-17 lumpectomy plus radiation group, bolstering confidence in that statistic and allowing for indirect comparisons between trial results.
The resulting recurrence rates from the trial were 25% with lumpectomy, 13% with lumpectomy plus radiation therapy, and 8% with lumpectomy plus radiotherapy plus tamoxifen for 5 years.
"Clearly, tamoxifen does have an effect on the rate of recurrence," said Morrow. As with the NSABP B-17 trial, however, more information is needed to specify which groups of women could be treated with surgery and radiotherapy alone, without tamoxifen.
Others continue to question the benefit derived from both postoperative tamoxifen and postoperative radiation therapy for specific subsets of women with DCIS. In a retrospective analysis, Melvin Silverstein, M.D., and his colleagues at the University of Southern California School of Medicine, Los Angeles, found that radiation therapy was not associated with a lower recurrence rate among DCIS patients whose excised lesions include a margin of normal tissue around them that is 10 millimeters or larger.
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Radiation: Yes or No?
Although these conclusions were based on a retrospective case series and not a randomized clinical trial, they raise the question whether radiation therapy is necessary for all women with DCIS who have breast-conserving surgery. Silversteins team points out that their patients with margin widths of 10 millimeters or more who had neither postoperative radiation nor tamoxifen had a rate of recurrence similar to the low rates seen by women in both the NSABP radiation group and the NSABP radiation-plus-tamoxifen group. They concluded that additional postoperative therapy, including both radiation therapy and tamoxifen, is unlikely to benefit women with margins greater or equal to 10 millimeters.
One source of agreement among presenters was that the intensity of treatment should be in accordance with risk, and that patients should be well informed of their options and risks. It is the amount of risk that each DCIS patient carries that remains unknown and is the goal of future research.
Recent studies are broad steps toward delineating a gold standard of treatment for DCIS patients. But, Morrow said, "We need to continue to look toward our colleagues in the laboratory to give us better markers for the ultimate risk of breast cancer death."
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