2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

Ductal Carcinoma In Situ, and the Influence
of the Mode of Detection, Population
Characteristics, and Other Risk Factors
By Beth A. Virnig, PhD, MPH, Shi-Yi Wang, MD, MS, and Todd M. Tuttle, MD, MS
Overview: Approximately 25% of breast cancers in the United
States are diagnosed as ductal carcinoma in situ (DCIS). Rates
of DCIS have risen from 5.8 per 100,000 women in the 1970s to
32.5 per 100,000 in 2004. This pattern is generally attributed to
increased use of screening mammography. DCIS is a major
risk factor for invasive breast cancer, and considerable controversy
remains about whether DCIS should be considered a
direct precursor of invasive breast cancer. There is, however,
a general consensus that DCIS represents an intermediate
step between normal breast tissue and invasive breast cancer.
Although the majority of major risk factors are similar for DCIS
and invasive breast cancer, prognostic factors including estrogen
and progesterone receptor status and HER2 positivity
DUCTAL CARCINOMA in situ (DCIS) is noninvasive
breast cancer that encompasses a wide spectrum of
diseases ranging from low-grade lesions that are not life
threatening to high-grade lesions that may harbor foci of
invasive breast cancer. DCIS is typically classified according
to architectural pattern (solid, cribriform, papillary, and
micropapillary), tumor grade (high, intermediate, and low),
and the presence or absence of comedo necrosis. Approximately
25% of breast cancers diagnosed in the United States
are DCIS. 1
The fundamental question underlying treatment and detection
of DCIS is whether it should be considered a direct
precursor of invasive breast cancer. There is general consensus
that DCIS represents an intermediate step between
normal breast tissue and invasive breast cancer. However,
because of general treatment patterns and the recognition
that even a biopsy may remove an important portion of the
tumor, the natural history of untreated DCIS is unknown
and likely is unknowable. This article provides updates on a
report requested by the National Institutes of Health Office
of Medical Applications of Research, which is available at
www.ahrq.gov//clinic/epcix.htm and summarized by Virnig. 2
The report addresses key questions about the incidence of
DCIS and the associated risk factors, the effect of magnetic
resonance imaging (MRI) and sentinel lymph node biopsy
(SLNB) on patient outcomes, and the effect of tumor and
patient characteristics, surgery, radiation, and systemic
treatment on outcomes.
The incidence of DCIS has increased dramatically since
the early 1970s from 5.8 per 100,000 in 1975 to 32.5 per
100,000 in 2004. Yet, the rate of DCIS is considerably less
than the invasive breast cancer incidence, estimated to be
124.3 per 100,000 in 2004. 1 The incidence of the most
aggressive subtype of DCIS—comedo—has not increased as
rapidly as the less aggressive noncomedo form. It is not clear
whether these patterns reflect screening picking up more
noncomedo tumors or pathologists using the comedo classification
less often.
The increased risk of invasive breast cancer associated
with hormone replacement therapy (HRT) with estrogen
plus progestin is well established. The reported association
between HRT and DCIS is inconsistent across studies. 3-5
are less well studied but look to have similar value in both
cases. The use of postdiagnostic MRI, sentinel lymph node
biopsy, surgery, radiation, and endocrine therapy are all
evolving as evidence from randomized and observational
studies continues to accumulate. Treatment of DCIS requires
a balance between risk of overtreatment and undertreatment.
Ongoing studies are focusing on whether partial-breast irradiation
is as effective as whole-breast irradiation and whether
treatment with endocrine therapies can reduce the likelihood
of either invasive breast cancer or DCIS recurrence. In general,
treatment decisions should take into account the likelihood
that an apparent case of DCIS could harbor foci of
invasive disease.
The strongest evidence that the increased incidence of
DCIS can be attributed to the use of screening mammography
comes from eight population-based trials of mammography
screening. Mammographic screening consistently was
more likely to lead to the diagnosis of invasive breast cancer
than of DCIS—all trials reported that less than 20% of
screen-detected breast cancers were DCIS. There is considerable
evidence that the detection of DCIS is greatest at
baseline screening. For example, the breast cancer surveillance
consortium reported DCIS incidence of 150 per 1,000
screening mammograms on first screening and incidence of
0.83 per 1,000 for subsequent screening mammograms. 6
Although several trials have assessed the value of tamoxifen
or raloxifene for preventing DCIS, the trials, in reality,
were designed to assess the value of the agents for preventing
invasive breast cancer, with DCIS as a secondary outcome.
Two large, controlled trials showed that tamoxifen
had a protective role on the development of DCIS (and
invasive breast cancer), though the magnitude of effects
varied somewhat. 7,8 The Study of Tamoxifen and Raloxifene
(STAR) trial found 40% higher incidence of DCIS for women
treated with raloxifene than with tamoxifen. The study also
found both treatments decreased the risk of invasive breast
cancer by half. The women randomly assigned to raloxifene
had 36% fewer uterine cancers and 29% fewer blood clots
than the women assigned to tamoxifen. 9
The Continuing Outcomes Relevant to Evista (CORE)/
Multiple Outcomes of Raloxifene Evaluation (MORE) study
found significantly reduced incidence of invasive breast
cancer associated with raloxifene (hazard ratio [HR] � 0.41),
but a nonsignificant increase in the incidence of DCIS
among the treated women (HR � 1.78). 10 The inconsistent
effect of raloxifene and tamoxifen on DCIS and invasive
From the University of Minnesota School of Public Health and University of Minnesota
Medical School, Minneapolis, MN.
Authors’ disclosures of potential conflicts of interest are found at the end of this article.
Address reprint requests to Beth A. Virnig, PhD, MPH, University of Minnesota School of
Public Health, 420 Delaware Street SE, MMC 729, Minneapolis, MN 55455; email:
virni001@umn.edu.
© 2012 by American Society of Clinical Oncology.
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