Editorial

Ductal Carcinoma In Situ: How Much is Too Much?

Keerthi Gogineni, MD, MSHP

The increase in screening mammography over the last 4 decades has brought with it a dramatic increase in the incidence of
ductal carcinoma in situ (DCIS). In 2014, 63,000 women were diagnosed with DCIS in the United States, and they
accounted for 27% of breast cancer diagnoses.1,2
In this issue of Cancer, Shiyanbola et al3 report on the use of surgery and radiotherapy for the management of
416,232 women diagnosed with DCIS between 1998 and 2011. Using data from the National Cancer Data Base
(NCDB), the authors identify changing trends in treatment patterns and describe how care varies according to age, geogra-
phy, and ancestry/ethnicity. Using the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER)
database, a previously published study4 evaluated treatment trends for DCIS among 121,080 patients. SEER registries
represent almost 30% of new cancer diagnoses each year, and the NCDB represents approximately 70% of newly diag-
nosed cancer cases nationwide.5 Nearly a quarter of NCDB’s cancer cases are breast cancer cases, and just under 20% of
these cases are DCIS.6
Current standards of care for DCIS entail surgical resection followed by consideration of adjuvant radiotherapy to
reduce the recurrence risk for DCIS and invasive disease. Depending on the risk factors, adjuvant radiotherapy can consid-
erably reduce recurrence after breast conservation; however, it does not affect survival. Some women are offered adjuvant
endocrine therapy to reduce recurrence and as chemoprevention for the contralateral breast.
Shiyanbola et al’s findings3 affirm that most women with DCIS are treated with breast conservation (68%) in lieu of
mastectomy (32%). Of those who underwent breast conservation (n 5 284,923), two-thirds proceeded to undergo adju-
vant radiation. In this analysis, the authors demonstrate that the use of adjuvant radiation plateaued by 2007 at 71%.
Because of the absence of a survival benefit with adjuvant radiotherapy, this may reflect a shift toward the omission of radi-
ation for lower risk DCIS. The authors report that women living in the Midwest were more likely to undergo adjuvant
radiotherapy than women in the Northeast, whereas women in the West were less likely to undergo radiation; however,
we do not know whether the plateau in the use of adjuvant radiotherapy by 2007 varied by geography. It would be a con-
cern if this trend were taking place because of differential access to radiation treatment facilities depending on the area of
residence rather than intentional omission for low-risk lesions. A prior analysis of SEER data showed that the distance
from a radiotherapy facility did affect the likelihood of receiving radiation, but that analysis did not assess whether longer
distances were more likely in particular regions of the country.7 Notably, African and Hispanic women were less likely to
undergo adjuvant radiotherapy than their European counterparts.
In contrast to the possibility that the trend in adjuvant radiotherapy represents appropriate risk-adjusted de-escala-
tion of therapy, contralateral mastectomy rates have steadily risen.
Rates of contralateral mastectomy in the setting of DCIS reached 30% in 2010-2011 versus 9% in 1998-1999.
Importantly, the authors assert that mastectomy rates began to rise after 2005; however, readers should be careful to note
that the rates reported in Table 2 of the article include both unilateral mastectomy and contralateral mastectomy, and the
changing trend after 2005 was likely driven by contralateral mastectomy. Worni et al’s analysis of SEER data4 also demon-
strates a disturbing rise in contralateral mastectomy but reassuringly reveals that mastectomy performed for the treatment
of DCIS declined from 27% in 1996-2000 to 20% in 2006-2010. The annual trend for mastectomy reported by Worni
et al does flatten and slightly rise after 2006. Rates of contralateral mastectomy procedures in the NCDB database, most of
which were presumably prophylactic, rose steadily throughout the time period analyzed (this was consistent with the
SEER analysis). This trend toward more aggressive surgery despite the overwhelmingly positive prognosis of DCIS begs a

Corresponding author: Keerthi Gogineni, MD, MSHP, Winship Cancer Institute, Emory University School of Medicine, 1365C Clifton Road, Suite 4009, Atlanta,
Georgia 30322; Fax: (404) 778-5530; keerthi.gogineni@emory.edu
Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia.

See referenced original article on pages 2810-8, this issue.

DOI: 10.1002/cncr.30107, Received: April 22, 2016; Accepted: April 25, 2016, Published online May 31, 2016 in Wiley Online Library (wileyonlinelibrary.com)

2780 Cancer September 15, 2016


closer examination of provider and patient decision mak-
ing, especially in the era of routine screening mammog-
raphy. Unfortunately, these findings echo concerns that
the treatment of DCIS often fails to be proportionate to
the biological risk.
Although the authors describe the characteristics of
women diagnosed with DCIS between the years of 1998
and 2011, they do not describe the characteristics of the
DCIS diagnosed. Narod et al’s SEER analysis of 108,196
women8 reinforced DCIS as a biologically diverse entity in
which certain features (high grade, large size, comedo ne-
crosis, and estrogen receptor–negative status) and patient
characteristics (black race and an age at diagnosis less than
35 years) predict higher risk.8 Worni et al’s SEER analysis4
showed that 35% of those who underwent mastectomy
had tumors  15 mm, and 32% of those who underwent
mastectomy had either low- or intermediate-grade tumors;
this suggests that mastectomy was pursued over breast con-
servation even when the lesion was lower risk. Shiyanbola
et al3 did adjust for size and grade in their multivariate
logistic regression analysis of the likelihood of receiving
specific treatment modalities according to age group, year
of diagnosis, ancestry/ethnic group, and geographic region.
One cannot assess whether mastectomy was indicated on
account of multifocal DCIS because focality is not a vari-
able that is available in the NCDB or SEER.
Could mastectomy rates be attributed to other high-
risk features such as a younger age at diagnosis or a higher
incidence of estrogen-negative DCIS? Mastectomy rates
overall did decrease the older a woman was at the age of
diagnosis. It is possible that younger women are more
inclined to undergo mastectomy and contralateral mastec-
tomy because of higher rates of BRCA mutations, but
because of the relatively low frequency of carriers, this is
unlikely to entirely explain the age-related trend.
Most DCIS is estrogen receptor– and progesterone
receptor–positive.9 The hormone receptor status of DCIS
is frequently missing in SEER and NCDB, so it is not pos-
sible to describe changes over time in the pattern of hor-
mone receptors. Information on the use of adjuvant
endocrine therapy is often incomplete, and because of the
absence of a survival benefit with the use of adjuvant en-
docrine therapy in the treatment of DCIS, one cannot
extrapolate that the use of endocrine therapy is a reliable
proxy for the hormone receptor status. Regardless, a
higher incidence of estrogen/progesterone-negative DCIS
is also unlikely to be driving mastectomy rates.
Shiyanbola et al3 report that the odds of undergoing
breast conservation are highest in the Northeast. Notably,
the odds of mastectomy are highest in the West, where the
Cancer September 15, 2016
Ductal Carcinoma In Situ Trends/Gogineni
odds of adjuvant radiotherapy after breast conservation
are also the lowest. Contralateral mastectomy rates are
also highest in the West. Together, these findings warrant
further investigation into this geographic variation in pat-
terns of care.
Although the authors cautiously suggest that the role
of contralateral mastectomy in DCIS is debatable, there is
no evidence to support the use of contralateral mastectomy
in the management of DCIS absent a known genetic pre-
disposition for a second primary breast cancer. Despite
excellent prognosis, women with DCIS report fears of re-
currence similar to those of women with invasive breast
cancer. Prior survey work has demonstrated that in nearly
500 patients who had a diagnosis of early-stage invasive dis-
ease or DCIS, one-third of respondents with DCIS were as
likely as women with invasive disease to believe that they
could develop distant metastases and die of breast cancer.10
Although women may opt to pursue prophylactic mastec-
tomy because of personal preference or cosmesis goals, we
must ensure that the decision is not being made because of
a misunderstanding of the biology of DCIS or an overesti-
mation of the risk of a second primary.
Overall, the odds of postmastectomy reconstruction
did increase with time among all 3 racial/ethnic groups;
reassuringly, this likely reflects increased access and health
insurance coverage for this procedure. The odds of recon-
struction remained highest in the Northeast and highest
for women of non-Hispanic European descent.
The natural history of DCIS remains a black box
because prospective data on the role of active surveillance
in survival have been lacking.11 The limited data available
require cautious interpretation; up to 30% of women
went on to develop invasive disease among those cases in
which the pathology review of the biopsy reclassified be-
nign disease as DCIS. Moreover, core biopsy is imperfect
and may miss invasive disease that is uncovered only with
surgical excision. The randomized phase 3 LORIS (Low-
Risk DCIS) trial is underway in the United Kingdom,
and the LORD (Management of Low-Risk DCIS) study
of the European Organization for Research and Treat-
ment of Cancer should shed light on whether a surveil-
lance approach after core biopsy for low- and
intermediate-risk DCIS is acceptable.12
There is a growing consensus that a nomenclature
appropriately reflecting the biological characteristics of
DCIS could limit aggressive surgical treatment and
reverse the trend of unnecessary prophylactic surgery by
reducing the psychological burden associated with a diag-
nosis of carcinoma. Our colleagues in endocrinology and
pathology have taken a formidable first step in
2781
Editorial
reclassifying an indolent variant of thyroid carcinoma.13
This study adds to the growing body of evidence showing
that we have more work to do to align patient preferences
for treatment with risk. Hopefully that as data emerge
from studies such as LORIS, we can maximize the benefit
and minimize the harm of screening mammography to
develop more judicious recommendations for the treat-
ment of DCIS that enable patients with low-risk lesions to
undergo less invasive treatment.
FUNDING SUPPORT
No specific funding was disclosed.
CONFLICT OF INTEREST DISCLOSURES
The author made no disclosures.
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