In the May, 1997, issue of Oncology News International , the updated
eight-year results of NSABP protocol B-17 were reported as presented by
Dr. Bernard Fisher in Paris. B-17 randomized patients with ductal carcinoma in
situ (DCIS) into two groups: One group received excision only, the other
excision plus postoperative radiation therapy.
The NSABP concluded that all subsets regardless of grade, size, or margin
status were benefited by irradiation, and they recommended that all breast
conservation patients with DCIS receive postoperative irradiation. However,
although this was a prospective randomized trial, the pathologic features
cited by the author to reach these conclusions were analyzed retrospectively.
Many of the significant prognostic features of DCIS that we have documented
in our own studies (size, margin width, nuclear grade)[2,3] were not tabulated
prospectively by the NSABP and were not available at the time of original
analysis. In fact, at the time of retrospective analysis, 27% of the
entire B-17 study population was unavailable for pathologic evaluation.
In the original study, all tissue was not submitted and sequentially
processed. There were no guidelines regarding size measurement, specimen
radiography, or mammographic-pathologic correlation. Margins were defined
as free (clear) when tumor was not transected. In other words, in some
cases, only a few fat cells separated DCIS from the inked margin.
In 40% of cases, no tumor size was provided by the initial pathologist,
and, therefore, size could not be determined prospectively nor accurately
Possible differences in outcome (local recurrence) were also obscured
by the pathologic definitions, which created minimally divergent comparison
groups such as DCIS with one third or fewer of ducts exhibiting comedo
necrosis versus one third or more, and which pooled nuclear grade (NG)
I and II lesions with or without necrosis versus NG III DCIS.
Our database, including more than 440 conservatively treated DCIS patients[3,5-7],
has led us to a diametrically opposite conclusion. Our DCIS cases were
fully evaluated prospectively for grade, size, and margin status, and we
have defined those features to accentuate, not diminish, the differences
in the subgroups.
We found that irradiation provided no significant benefit in local control
for low-grade DCIS (NG I with or without necrosis) and for all DCIS regardless
of grade if the margins were greater than 10 mm or the re-excision was
negative for residual DCIS (see figures).
Irradiation did provide a mean 13% benefit reduction in local recurrence
rate in subsets of DCIS characterized by narrower margins, larger size,
and/or higher grade (Van Nuys Prognostic Index scores 5,6,7). [See reference
3 for a description of the Van Nuys Prognostic Index.]
Like all other studies of irradiation for DCIS except B-17, half of
the local recurrences were invasive regardless of radiation therapy. Longer
follow-up shows that the differences in recurrence rates between irradiated
and nonirradiated groups has begun to diminish, a feature suggested by
prior studies of irradiation for DCIS.  Finally, in our patient population,
invasive recurrences in the irradiated group were three times as large
as in the nonirradiated group (35 mm versus 11 mm).
For patients most at risk of recurrence, those with NG III DCIS with
any comedo necrosis, size greater than 40 mm, and margins less than 1 mm
(Van Nuys Prognostic Index scores 8,9), radiation therapy made a major
impact, reducing local recurrences from 100% at four years to 60% at six
years, but clearly this is a pyrrhic achievement unacceptable in clinical
Ours was not a randomized trial, but our methods of patient selection
and clinical judgment are a more realistical reflection of actual clinical
practice; moreover, we could not control the grade or the size of the DCIS,
and patients frequently self-selected their mode of therapy regardless
of recommendations. Our study does not compare treatments but, rather,
prognostic factors over which we have no control.
We conclude that the morphologic heterogeneity of DCIS reflects a similar
biologic heterogeneity and that therapies should be tailored to fit the
actual risks of local recurrence. Although our methods must be validated,
we have every expectation that they will be in programs now developing
in other centers.
1. Fisher ER, Costantino J, Fisher B, et al: Pathologic finding from
the National Surgical Adjuvant Breast Project protocol B-17: Intraductal
carcinoma (duct carcinoma in situ). Cancer 75:1310-1319, 1995.
2. Lagios MD, Margolin FR, Westdahl PR, et al: Mammographically detected
duct carcinoma in situ: Frequency of local recurrence following tylectomy
and prognostic effect of nuclear grade on local recurrence. Cancer 63:619-624,
3. Silverstein MJ, Lagios MD, Craig PH, et al: A prognostic index for
ductal carcinoma in situ of the breast. Cancer 77:2267-2274, 1996.
4. Fisher B, Costantino J, Redmond C, et al: Lumpectomy compared with
lumpectomy and radiation therapy for the treatment of intraductal breast
cancer. N Engl J Med 328:1581-1586, 1993.
5. Silverstein MJ, Lagios MD, Waisman JR, et al: Outcome after local
recurrence for patients with ductal carcinoma in situ of the breast. Proc
Am Soc Clin Oncol 16:129A, 1997.
6. Silverstein MJ, Lagios MD: Use of predictors of recurrence to plan
therapy for DCIS of the breast. Oncology 11:393-410, 1997.
7. Lagios MD, Silverstein MJ: Ductal carcinoma in situ. The success
of breast conservation therapy: A shared experience of two single institutional
nonrandomized prospective studies. Surg Oncol Clinics North Am 6:385-392,
8. Solin L, Kurt J, Fourquet A, et al: Fifteen-year results of breast-conserving
surgery and definitive breast irradiation for the treatment of ductal carcinoma
in situ (intraductal carcinoma) of the breast. J Clin Oncol 14:754-763,