Treatment of DCIS Called ‘Dilemma of the ’90s’

FLORENCE, Italy—Although breast-conserving surgery coupled with radiotherapy has been advocated as the treatment of choice for ductal carcinoma in situ (DCIS) , management remains controversial.

The chief dilemmas, as outlined by Melvin Silverstein, MD, at the First European Breast Cancer Conference, are whether some women with this heterogeneous disease might be better served by mastectomy than local excision and whether others who do undergo local excision might be able to forego radiotherapy. Dr. Silverstein is director of the Breast Center and professor of surgery at the University of Southern California.

Two decades ago, DCIS represented fewer than 1% of all new cases of breast cancer, but today it accounts for 13% of cases. Dr. Silverstein noted that the widespread use of mammography has changed DCIS from an unusual disease that was diagnosed clinically to a common disease that is almost always subclinical and nonpalpable.

In addition, he commented, DCIS has evolved from a disease that was defined strictly in architectural terms to one that is now better defined biologically.

Describing a series of nearly 800 DCIS patients that he and his colleagues treated at The Breast Center at Van Nuys (California), Dr. Silver-stein said that nearly half of local recurrences were invasive and that 93% of all local recurrences occurred at or near the primary lesion. This underscores the difficulty of achieving complete excision of a nonpalpable, nonvisualizable lesion, he commented.

Nonetheless, because DCIS is most commonly unicentric, albeit with skips, complete excision is a real possibility, Dr. Silverstein said. He noted his increasing preference for radial incisions, which take advantage of the segmental distribution of the disease.

“The first excision is your best chance at complete excision,” Dr. Silverstein said. He recommends either stereotactic core biopsy or Mammotome biopsy (which incorporates vacuum to facilitate removal of larger samples) to first determine the diagnosis. If the surgeon knows the lesion is malignant, he or she can then be more aggressive in the amount of breast tissue removed.

Dr. Silverstein added, however, that “breast surgeons are thinking not only as oncologists but also as plastic surgeons. In the DCIS business, it’s a constant battle between margins vs cosmesis—you’re trying to completely excise the lesion but nevertheless retain a usable, functional breast that will make the patient happy.”

Identification of those factors linked to a high likelihood of local recurrence is the critical prerequisite for selecting potential mastectomy candidates. “In our experience, the higher the grade, the more likely the lesion is to recur and the quicker it recurs,” he stressed. Tumor size and margin width are also significant prognostic features.

In the Van Nuys series, the DCIS patients most at risk of recurrence (those with nuclear grade III tumors with any comedo necrosis, size greater than 40 mm, and margins less than 1 mm) had high rates of local recurrence at 5 years—60% with radiotherapy and 100% without—suggesting that mastectomy may be a better option in these patients.

The anatomic distribution of the tumor and the adequacy of surgical incision go hand in hand, he said. “If you have a very large lesion that can’t be completely excised, you’re going to get local recurrence,” he noted. “Only recently have we begun to appreciate that the surrounding tissue may look morphologically normal under the microscope but may already harbor the genetic changes that are necessary to become DCIS or even invasive cancer.”

The Van Nuys experience also revealed that only 2 of 364 patients who underwent axillary node dissection were node-positive in the absence of invasive disease in the breast. “So I would say that axillary node dissection is absolutely unnecessary for patients with DCIS,” Dr. Silverstein contended. However, he advised performing sentinel node biopsy for patients with DCIS large enough to warrant mastectomy.

Challenging NSABP B-17

Dr. Silverstein challenged the NSABP B-17 study’s conclusion that local excision plus radiotherapy is always more appropriate than local excision alone. “The problem is that they didn’t do an adequate subgroup analysis, and there very well may be some patients you can treat with excision alone,” he said. Radiation therapy may benefit some subgroups by only a small amount, he added, “and we need to know who they are.”

Although postoperative radiotherapy delayed the onset of local recurrence in the Van Nuys series, Dr. Silverstein emphasized that, after 10 years, the curves started to converge.

For those with wide excisions, there was no significant difference in local recurrence rates with or without radiotherapy. Margins were carefully measured in this series, he said, either by direct measurement or by ocular micrometry.

“There’s a dramatic advantage for radiation therapy when we leave DCIS behind,” Dr. Silverstein said, “but there’s almost no benefit from radiation therapy for patients with margins of 10 mm or more.”

More recently, Dr. Silverstein said, the NSABP B-24 study has found that tamoxifen (Nolvadex) affords approximately a 5% benefit when added to local excision and radiotherapy. “This probably will lead the NSABP to recommend that most patients with DCIS get breast-conserving surgery, radiation therapy, and tamoxifen,” he predicted.

Dr. Silverstein’s concern about the idea of “radiation therapy (and now possibly tamoxifen) for everybody” stems from the potential side effects of radiation therapy, such as radiation fibrosis, difficulty in interpreting postradiation mammog-raphy, etc, not to mention the cost and time involved in radiation therapy.

“If you give irradiation to patients with DCIS, it prevents you from using radiation therapy in patients who later develop invasive breast cancer, and it also makes state-of-the-art skin-sparing mastectomy more difficult,” he added.

And, he reminded the audience, “no study has shown any difference in long-term outcome in terms of survival, no matter what treatment you use.”