What is the optimal local and systemic therapy for DCIS? Do all DCIS patients need radiation therapy? What is the optimal endocrine therapy for DCIS?

OVERVIEW: The widespread use of screening mammography has resulted in an increasing fraction of breast cancer patients presenting with early-stage disease, including ductal carcinoma in situ. One of the most controversial current management issues for DCIS involves the role of lumpectomy without radiation therapy. The criteria for this approach is not well-defined. Since DCIS patients are at increased risk for a second breast cancer, current clinical trials are addressing the role of endocrine intervention. A particularly salient issue — in view of the recently reported ATAC trial results — is whether aromatase inhibitors can replace tamoxifen in postmenopausal women.

NSABP PROPOSED TRIAL COMPARING ANASTROZOLE TO TAMOXIFEN IN DCIS

The driving force of current research is to move away from the concept that DCIS is simply a surgical problem — and that if you obtain 10 mm margins, the patient is cured and no adjuvant therapy is needed. It’s not really important to argue about whether there’s a set of patients who don’t need radiation therapy.

Even if we take out the index DCIS, the risk for these women to have another tumor in either breast in the future is at least as high or higher than the risk for women in the NSABP P-1 prevention trial. Chemoprevention in DCIS is an important issue, and we need to find out how to do this best.

Nobody believed when we started with tamoxifen that it would be a "home run" and end all inquiry. As enormously successful as the Prevention Trial was in reducing the incidence of cancer by 50%, everybody understands that there must be a more effective or safer drug.

The ATAC trial is answering the question about anastrozole in invasive breast cancer. We need to ask the same question in non-invasive disease. We are focusing on anastrozole, because there are the two studies in advanced disease that show that it’s equal or superior to tamoxifen.

—Richard Margolese, MD

TREATMENT OF DCIS PATIENTS WITH POSITIVE SENTINEL NODES

This is an extremely challenging issue. There clearly are patients with DCIS diagnosed by core biopsy techniques who have invasive cancer in their final specimens. Once they have invasive cancer, I don’t consider them in the DCIS pool. So the first step when a "DCIS patient" has a positive node by H & E is to go back and ask the pathologist to make extra sections and look very hard for invasive carcinoma. Moffitt has looked retrospectively at DCIS patients with IHC-positive nodes and found no surv i val impact, but that study didn’t have much statistical powe r. We have no reliable data to guide us in that situation, which is the reason I don’t do IHC in routine practice.

—Monica Morrow, MD

NATURAL HISTORY

In premenopausal women, DCIS is over-diagnosed. It is likely that only one in five, if undetected, would prog ress to become inva s i ve b reast cancer. But having detected it, we then have to treat it. One of the most dishonest things about promoting mammographic screening for women under the age of 50 is the idea of, "Come for screening. We’ll save your life and save your breast." Because DCIS is often outside one quadrant, the breast is not saved. So you have this extraordinary paradox that women think DCIS is early breast cancer. Yet, in the U.K. and the U.S.A., about 40% of premenopausal women with DCIS end up having a mastectomy. W h e reas, if it was left to appear as an inva s i ve breast cancer, the treatment would be a lumpectomy. No one can explain that mismatch.

—Michael Baum, ChM, FRCS

SELECTION OF DCIS PATIENTS FOR RADIATION THERAPY

I have a reputation for not wanting to give radiation to any DCIS patient, but that’s not true. We recommend it to many, but not all, patients. It’s relatively expensive and it’s a bit inconvenient. Patients have to come five days a week for at least five weeks. In some patients, we see significant radiation fibrosis, although much less in the last five or six years.

Also, if you give radiation therapy for DCIS and you get an invasive recurrence, radiation can’t be given again. If you don’t give radiation and there is an invasive recurrence, you can excise and irradiate. Another consideration is that if you end up having to do a skin-sparing mastectomy for an invasive recurrence, it’s a lot more difficult after radiation because of secondary vascular changes.

— Melvin Silverstein, MD

NSABP TRIALS B-17 AND B-24: RADIATION THERAPY AND TAMOXIFEN FOR DCIS

Our randomized trials demonstrate that, no matter what the margin difference or histologic subtype, there is a clear benefit from the use of radiation therapy. There is also a clear-cut benefit from tamoxifen for both tumor recurrence and reduction in risk for contralateral breast cancers. DCIS patients are at high-risk for contralateral breast cancers, and tamoxifen reduces that risk by more than 50%. The quest to identify patients who can avoid radiation therapy is very reasonable. The problem is that even an excellent observational series is potentially fraught with methodologic bias that can produce flawed results or conclusions. This isn’t a surgeon’s disease. It is a woman’s disease. And if you have a woman in front of you who has the information available today, I feel that offering radiation therapy increases her chance of being in that zero group.

—Lawrence Wickerham, MD

NSABP B-17: PHASE III RANDOMIZED STUDY OF POSTOPERATIVE RADIOTHERAPY FOLLOWING SEGMENTAL MASTECTOMY AND AXILLARY DISSECTION IN PATIENTS WITH NONINVASIVE INTRADUCTAL ADENOCARCINOMA OF THE BREAST CLOSED PROTOCOL

Fisher B et al. Lumpectomy compared with lumpectomy and radiation therapy for the treatment of intraductal breast cancer. N Engl J Med 1993; 328:1581-1586. Abstract

NSABP B-24: PHASE III RANDOMIZED TRIAL OF ADJUVANT TAMOXIFEN VS PLACEBO FOLLOWING BREAST IRRADIATION IN PATIENTS WHO HAVE UNDERGONE LUMPECTOMY FOR NONINVASIVE INTRADUCTAL CARCINOMA (DCIS) OF THE BREAST CLOSED PROTOCOL

Fisher B et al. Tamoxifen in treatment of intraductal breast cancer: National Surgical Adjuvant Breast and Bowel Project B-24 randomised controlled trial. Lancet 1999;353(9169):1993-2000. Abstract

NSABP trials of patients receiving lumpectomy for DCIS. Cumulative incidence of all invasive and noninvasive events in the ipsilateral and contralateral breast in NSABP B-17 and B-24 studies. Note the stepwise improvements in outcome with the addition of XRT and tamoxifen to lumpectomy for DCIS. Modified from Lancet 1999;353(9169):1993-2000. Abstract

PROPOSED IBIS 2 TRIAL: INTERNATIONAL BREAST INTERVENTION STUDY 2

RTOG-9804; RTOG-DEV-1026: PHASE III RANDOMIZED STUDY OF TAMOXIFEN WITH OR WITHOUT RADIOTHERAPY IN WOMEN WITH DUCTAL CARCINOMA IN SITU (DCIS) OF THE BREAST OPEN PROTOCOL

STUDY CONTACT Barbara L. Smith, Chair, Phone: 617-724-4800 Beryl McCormick, Chair, Phone: 212-639-6828 Radiation Therapy Oncology Group

PROPOSED NSABP DCIS TRIAL: TAMOXIFEN VERSUS ARIMIDEX IN POSTMENOPAUSAL PATIENTS WITH DUCTAL CARCINOMA IN SITU

Margolese R. Rationale for proposed National Surgical Adjuvant Breast and Bowel Project (NSABP): DCIS Trial. Tamoxifen versus Arimidex® (anastrozole) in postmenopausal patients with ductal carcinoma in situ. Poster, 2001 Miami Breast Cancer Conference. Full-Text

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