HOLLYWOOD, FL—For the first time, new guidelines for the treatment of ductal carcinoma in situ (DCIS) call for a determination of hormone status.
“The treatment of ductal carcinoma in situ has, of course, evolved over the last decade so that most women are now able to be treated with breast-conserving surgery,” noted Stephen E. Edge, MD, Chair of the Department of Breast and Soft Tissue Surgery at Roswell Park Cancer Institute.
“The change that we have made this year in this guideline, however, is to recommend that estrogen and progesterone receptors be evaluated in women with ductal carcinoma in situ. Prior to this time there had not been any evidence to support a measurement of estrogen receptor in women with DCIS.”
In presenting the guideline here at the 9th conference on Clinical Practice Guidelines and Outcomes Data in Oncology of the National Comprehensive Cancer Network, Dr. Edge said the rationale for the new treatment algorithm was based on the results of the National Surgical Adjuvant Breast and Bowel Project Protocol B24 results, a landmark trial that looked at the value of tamoxifen in women treated by lumpectomy with radiation therapy.
In that trial, 804 women were randomized to receive either tamoxifen or placebo after treatment with lumpectomy to a negative surgical margin followed by full breast radiation therapy.
“Overall, tamoxifen reduces the risk of ipsilateral ductal carcinoma in situ recurrence, as well as invasive recurrences and reduces the rate of a contralateral breast cancer, both DCIS and invasive cancer,” Dr. Edge said.
“When investigators analyzed the information on the basis of estrogen-receptor expression, 482 of the women who were tested had a positive estrogen receptor and 146 had negative estrogen receptors.”
“The benefit of tamoxifen was mostly limited to those individuals who had estrogen-receptor positive DCIS,” he said.
There was about a 59% reduction in the relative risk of recurrence, which was highly significant, he added. For women who had estrogen-receptor negative disease, there was about a 20% reduction in the relative risk of recurrence, but that did not reach statistical significance.
Dr. Edge noted that if the tissue was sampled at the local hospital, there appeared to be a greater likelihood of a negative estrogen-receptor finding than if the analysis was performed at a central testing facility.
“The NSABP researchers pointed out that the number of events in estrogen-receptor negative women was too small to rule out a small benefit,” said Dr. Edge, who is also Professor of Surgery at State University of New York at Buffalo.
Impact on Therapy?
“How does this impact on our therapy, and how have we revised the guideline?,” he asked.
“The guideline committee felt that these data demonstrated that hormone-receptor status would provide stronger support for the use of tamoxifen, an area where there is often a difficult and time-consuming discussion with patients about the relatively low benefits and substantial toxicities of tamoxifen.”
“The guideline for tamoxifen use, in addition to suggesting that the estrogen receptor be determined, was revised to read that patients should be considered for tamoxifen especially for those with estrogen-receptor positive DCIS.”
“The benefit of tamoxifen for estrogen-receptor negative disease is uncertain. There is certainly a need for further data and testing of other agents and participation in clinical trials,” Dr. Edge said.
Len Lichtenfeld, MD, Acting Deputy Chief Medical Officer for the American Cancer Society, noted that several years ago there were few considerations for treatment options after surgery to remove DCIS, and that the NCCN guidelines show that there are options to consider other than just surgery.
“The treatment algorithm allows doctors to follow the pathway and determine if there are other things that can be done for the patient to enhance their survival,” he said.
Dr. Edge also described two other areas in the guidelines where changes have been made in treating women with DCIS. The guideline committee, he said, decided to refine recommendations for standards for pathologic analysis of specimens.
“To date we have not recommended pathology standards in our guideline at all,” he said. “The use of breast-conserving surgery is of course predicated on achieving a negative margin. Patients who have a positive margin at excision should undergo further surgery, either a repeat excision usually directed to the direction of the positive margin by the original pathology or in some cases by mastectomy.”
“The guidelines have now been revised to stipulate specific issues regarding margin evaluation.”
It is well known that achieving a negative margin has an impact on outcome, Dr. Edge said, noting a series of studies that demonstrate that women who have a negative margin have a lower risk of local failure than women who have a positive margin.
Dr. Edge noted that the new NCCN guideline added a footnote stipulating that the margins be oriented by the surgeon on the surgical specimen, that the pathologist describe both the gross and microscopic margin and report the distance, orientation, and type of tumor in relation to the closest margin.
Sentinel Node Biopsy
The new guidelines also consider the use of sentinel lymph node biopsy with neoadjuvant chemotherapy.
“Sentinel node biopsy has now been accepted across the United States by most authorities as a standard option for axillary staging in breast cancer,” he said.
“Most authorities feel that as a high level of accuracy that there is a low risk of axillary failure when axillary node dissection is omitted for women with negative lymph nodes and that sentinel node biopsy has minimal morbidity when compared with full axillary lymph node dissection.”
He said that new studies suggest that sentinel lymph node biopsy appears to be accurate when used with neoadjuvant chemotherapy with larger tumors.
“Therefore, we have revised the guideline for the use of sentinel node biopsy,” Dr. Edge said.
“We have recommended at this time that core biopsy of the breast and fine needle aspiration or biopsy of clinically positive axillary lymph nodes be considered, but we have now suggested that we use what we consider sentinel lymph node biopsy for women undergoing neoadjuvant chemotherapy if the lymph nodes are clinically negative.”
“And then following chemotherapy that the patient who is either undergoing mastectomy or breast-conserving surgery have axillary lymph node dissection omitted if the sentinel lymph node biopsy was negative prior to the initiation of chemotherapy,” he continued.
“This does represent a change in our practice and in our guidelines—one which engendered a fair amount of discussion in our guideline committee and one which we think will significantly affect practice.”
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