400
Chapter 11
tamoxifen in the treatment of DCIS showed a nonsignificant
reduction in all breast events with the addition of tamoxifen
and a RR reduction of 22% after 53 months of follow-up.
414
The NSABP trial on the use of tamoxifen and radio-
therapy in DCIS showed benefit, mainly due to reduction in
ipsilateral recurrent invasive carcinoma.
415
The 7-year risk
of local recurrence in the treated breast after lumpectomy
with radiation was reduced from 11.1% without tamoxifen
to 7.7% with tamoxifen (
p
=
0.02). The risk of all (ipsilateral
and contralateral) breast cancer events was reduced from
16.9% to 10.0% (
p
=
0.0003). DCIS patients received radio-
therapy and were then randomized to tamoxifen (20mg/day)
or placebo. After just over 6 years of follow-up, a significant
reduction in all new breast cancer events was reported in the
tamoxifen group compared with the placebo group. In a re-
cent published follow-up study on the NSABP B24 trial with
a median follow-up of 14.5 years,
416
it was reported that ad-
juvant tamoxifen significantly reduced the ipsilateral, as well
as contralateral, risk of DCIS recurrence and/or progression
to invasive breast carcinoma by about 50% in patients treated
with lumpectomy and radiation, and that the benefit was re-
stricted to patients with ER-positive DCIS (defined as those
with an Allred score of 3 or more). Using this cutoff, 76% of
DCIS were ER positive. Results for PR were comparatively
less predictive of benefit. Thus, patients with ER-positive
DCIS treated with tamoxifen (vs. placebo) showed signifi-
cant decreases in subsequent breast cancer at 10 years (HR,
0.49;
p
< 0.001) and follow-up (HR, 0.60;
p
=
0.003), which
remained significant in multivariate analysis (HR, 0.64;
p
=
0.003). Results were similar, but less significant, when sub-
sequent ipsilateral and contralateral breast carcinomas were
considered. Thus, it is likely that SERM therapy will be rou-
tinely established in the treatment of appropriately selected
ER-positive breast carcinoma patients. Based on data from
the NSABP STAR trial, raloxifen offers less protection than
tamoxifen for postmenopausal women.
417
Summary of Treatment Recommendations
Patient survival, the appropriate endpoint for most malignant
neoplasms, is the measure by which various therapy regimens
are assessed. However, survival is of almost no utility in DCIS
since the breast cancer–specific survival in DCIS exceeds
95%, regardless of treatment.
418
The
low mortality
due to
DCIS itself is reflected in the 2009 NIH Consensus Statement
recommending elimination of the “anxiety-producing term
‘carcinoma’ from the description of DCIS.”
419
Recurrence of
disease in either the
in situ
or the invasive form, particularly
in the ipsilateral, but also in the contralateral, breast is the
most commonly assessed data endpoint. In general, approxi-
mately one-half of local recurrences in DCIS cases are inva-
sive carcinoma. Thus, the primary goal of treatment of DCIS
is to reduce the risk of local recurrence.
The relatively
high morbidity
of at least some forms of the
disease can be assessed by the wide variety of treatment rec-
ommendations that are available to any patient with DCIS.
In current practice, DCIS is most commonly diagnosed as a
result of the detection of a mammographic abnormality on
Concurrent Proliferative Lesions
and Breast Conservation
Adepoju et al.
413
studied the relationship of concurrent
atypical duct and lobular hyperplasia and of LCIS to the
risk of breast recurrence in women with DCIS treated by
breast conservation therapy. Approximately 9.3% of the pa-
tients also had microinvasive ductal carcinoma, and about
70% received radiotherapy in addition to surgical excision.
Follow-up ranged from 0.3 to 29 years (median, 8.6 years).
Eighty patients had concurrent significant proliferative le-
sions consisting of atypical duct hyperplasia (
n
:54) or atypi-
cal lobular hyperplasia (ALH) or LCIS (
n
:10). During the
course of follow-up, 43 patients (14%) had breast recur-
rences, 90% of which were detected by mammography.
The risk of local failure was significantly lower in women
who had radiotherapy (8.4%) than in those not irradiated
(29.5%), and the median time was significantly longer in ra-
diated patients (10 vs. 4.9 years). The presence of concurrent
atypical duct or lobular hyperplasia or of LCIS did not have
a significant effect on recurrence in the breast with DCIS.
However, these lesions were associated with a substantially
higher frequency of contralateral carcinoma, which oc-
curred 4.4 times more often in women who had atypical
duct hyperplasia associated with DCIS. The 15-year cumu-
lative risk of developing contralateral carcinoma was 19%
when atypical duct hyperplasia was present in the ipsilateral
breast, and 4.1% when atypical hyperplasia was absent (
p
<
0.01). An equally large differential was found for ALH and
LCIS coexisting with DCIS (15-year cumulative risk, 22.7%
vs. 6.5%), but the difference was not statistically significant.
Meta-analysis of Treatment
A meta-analysis of published reports compared recurrence
rates for patients with DCIS after treatment with one of
three modalities.
348
The summary recurrence rates were
1.4% (95% CI, 0.7 to 2.1), 8.9% (95% CI, 6.8 to 11.0), and
22.5% (95% CI, 16.9 to 28.2), respectively, for mastectomy,
lumpectomy with radiotherapy, and lumpectomy alone.
The proportions of invasive recurrence in each group were
76%, 50%, and 43%. The nearly threefold higher rate of re-
currence after lumpectomy without radiotherapy compared
with women who were radiated is especially striking in view
of the likelihood that excision alone was most often recom-
mended for patients with low grade, relatively small lesions
with negative margins. The authors observed that “patients
with risk factors of presence of necrosis, high-grade cyto-
logic features or comedo subtype were found to derive the
greatest improvement in local control” from the addition of
radiotherapy to conservation surgery.
Selective Estrogen Receptor Modulator in DCIS
The role of Selective EstrogenReceptorModulators (SERMs),
specifically tamoxifen, in managing DCIS has been inves-
tigated in the UK/ANZ DCIS trial and also in the NSABP
B24 trial. The UK/ANZ Trial comparing radiotherapy and
