2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

Ductal Carcinoma In Situ: Challenges,
Opportunities, and Uncharted Waters
By Abigail W. Hoffman, MD, Catherine Ibarra-Drendall, PhD, Virginia Espina, MS,
Lance Liotta, MD, PhD, and Victoria Seewaldt, MD
Overview: Ductal carcinoma in situ (DCIS) is a heterogeneous
group of diseases that differ in biology and clinical
behavior. Until 1980, DCIS represented less than 1% of all
breast cancer cases. With the increased utilization of mammography,
DCIS now accounts for 15% to 25% of newly
diagnosed breast cancer cases in the United States. Although
our ability to detect DCIS has radically improved, our understanding
of the pathophysiology and factors involved in its
progression to invasive carcinoma is still poorly defined. In
many patients, DCIS will never progress to invasive breast
cancer and these women are overtreated. In contrast, some
DCIS cases are clinically aggressive and the women may be
undertreated. We are able to define some of the predictors of
aggressive DCIS compared with DCIS of low malignant poten-
DUCTAL CARCINOMA in situ is defined as a breast
lesion in which neoplastic mammary epithelial cells
are confined to the mammary ductal-lobular system without
invasion into the surrounding stroma. DCIS accounts for
approximately 15% to 25% of all female breast cancers. The
primary clinical goal in the management of DCIS is to
prevent the development of invasive breast cancer. In order
to individualize treatment of DCIS, there is a need for
biomarkers to prospectively identify DCIS with aggressive
biologic potential.
DCIS is highly variable in its clinical presentation, pathology,
genetic/epigenetic alterations, and biologic potential. 1,2
Although DCIS is a heterogeneous disease, until recently,
treatment of DCIS was relatively uniform. There is emerging
evidence that DCIS has a wide range of biologic phenotypes;
however, we lack biomarkers to definitively identify
DCIS that will progress to invasive disease. As a result,
there is considerable debate regarding how best to manage
patients with DCIS. The current primary management
options for women with DCIS include lumpectomy plus
radiation therapy; total mastectomy, with or without sentinel
node biopsy, with or without reconstruction; or lumpectomy
alone followed by clinical observation. Mastectomy is
an effective therapy for most patients; however, for many
women it represents overtreatment, particularly those with
minimal lesions identified by mammography. Randomized
clinical trials comparing breast-conserving surgery and radiation
versus breast-conserving surgery alone show that
radiation therapy reduces local recurrence by approximately
50%. 3,4 Conversely, it is possible that a subgroup of patients
with DCIS may not benefit from radiation following breastconserving
surgery.
Women with biologically aggressive DCIS are at high risk
of local-regional recurrence or progression to invasive breast
cancer and are logically best served by mastectomy. However,
it is also clear that there are women with DCIS at a low
risk for local-regional recurrence and/or progression who
might be adequately treated by breast-conserving surgery
alone, without radiation therapy. Emerging evidence suggests
that there are also women whose DCIS is at such low
risk for recurrence or progression to invasive breast cancer
40
tial. However, our ability to risk-stratify DCIS is still in its
infancy. Clinical risk factors that predict aggressive disease
and increased risk of local recurrence include young age at
diagnosis, large lesion size, high nuclear grade, comedo
necrosis, and involved margins. Treatment factors such as
wider surgical margins and radiation therapy reduce the risk
of local recurrence. DCIS represents a key intermediate in the
stepwise progression to malignancy, but not all aggressive
breast cancers appear to have a DCIS intermediate, notably
within triple-negative breast cancer. Ongoing studies of the
genetic and epigenetic alterations in precancerous breast
lesions (atypia and DCIS) as well as the breast microenvironment
are important for developing effective early detection
and individualized targeted prevention.
that they might be observed following a diagnostic biopsy
and undergo “watchful waiting.” 5 However, at this time, we
cannot accurately predict the course of each patient’s DCIS.
Herein, we review our current understanding of 1) clinical
risk factors that predict local recurrence in patients with
DCIS treated with breast-conserving therapy, 2) evidence
for invasive breast cancers that potentially emerge from
intraepithelial neoplasia of lower grade than DCIS, and
3) molecular studies that aim to improve our understanding
of the biologic potential and diversity of DCIS lesions.
Clinical, Treatment, and Pathologic Risk
Factors That Predict Local Recurrence and
Invasion in Women with DCIS
Diagnosis and Prognosis
Until 1980, DCIS represented less than 1% of all breast
cancer cases. With the increased utilization of mammography
during the 1980s, DCIS now accounts for 15% to 25% of
newly diagnosed breast cancer cases in the United States. 6
Currently over 90% of DCIS is diagnosed by mammographic
examination alone; however, mammograms detect calcifications
and frequently do not identify the neoplasm size
accurately. 7 Precise preoperative evaluation is required to
determine the size and extent of the disease to optimize
surgical management. The recommended work-up and staging
of DCIS includes a history and physical examination,
bilateral diagnostic mammography, pathology review, and
tumor estrogen receptor (ER) determination. Breast Magnetic
Resonance Imaging (MRI) is increasingly being used
to evaluate DCIS; however, the exact use of breast MRI in
the preoperative management of DCIS remains a matter of
debate. 8
With a follow-up period of 25 years, it is estimated that
14% to 60% of women with untreated DCIS will develop
From Duke University, Durham, NC; George Mason University, Manassas, VA.
Authors’ disclosures of potential conflicts of interest are found at the end of this article.
Address reprint requests to Victoria Seewaldt, MD, Duke University, Box 2628, Room
221A MSRB, Durham, NC 27710; email: seewa001@mc.duke.edu.
© 2012 by American Society of Clinical Oncology.
1092-9118/10/1-10