Journal of the National Cancer Institute Monographs, No. 41, 2010 113
© The Author 2010. Published by Oxford University Press. All rights reserved.
For Permissions, please e-mail: email@example.com.
Ductal carcinoma in situ (DCIS) is a 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. The epidemiology of DCIS is
intertwined with that of invasive breast cancer. This article sum-
marizes information on the incidence and prevalence of DCIS and
its specific pathological subtypes, and on how incidence and preva-
lence are influenced by mode of detection, population characteris-
tics, and other risk factors. This review does not address issues of
DCIS incidence in women with a history of DCIS or breast cancer,
or predictors of second primaries or recurrence of DCIS.
Studies were sought from a wide variety of sources, including
MEDLINE via PubMed, Scirus, and Cochrane databases; websites
of the Sloane Project and of the International Breast Cancer
Screening Network; and manual searches of reference lists from
systematic reviews and consensus conferences. We include articles
published from 1965 through January 31, 2009.
We searched MESH headings, titles, and abstracts for the
terms Ductal Carcinoma In Situ, DCIS, noninfiltrating intraductal
carcinoma, carcinoma in situ, intraductal carcinoma, localized
breast cancer, and stage 0 breast cancer. We did not exclude stud-
ies by level of evidence. We reviewed abstracts to confirm eligible
target populations of female adults. We excluded studies of inva-
sive breast cancer only, non-breast cancers, and animal or in vitro
experiments and analysis of results from other publications, letters,
comments, and case reports. We abstracted 92 publications. This
article includes a highly abbreviated reference list.
The incidence of DCIS rose from 1.87 per 100 000 women from
1973–1975 to 32.5 per 100 000 in 2005 (1). This increase was
observed in all age categories with the greatest rise among those
older than 50 years of age. The increase in DCIS has not been
uniform across histological types. Comedo histology is associated
with a particularly high risk of recurrence and has been stable over
recent years, whereas low-grade DCIS, generally considered to be
less likely to recur or develop into invasive breast cancer, has
accounted for the majority of the recent increase (2) (Figure 1).
Demographic Variation in DCIS Incidence
The incidence of DCIS, like invasive breast cancer, is strongly
related to age. DCIS is extremely uncommon before age 35–39.
After that, the incidence rises steadily to a peak of 96.7 per 100 000
at ages 65–69 and then declines slowly until age 79 and steeply after
that. In contrast, invasive breast cancer peaks at age 75–79 with
incidence of 453.1 per 100 000 women (Figure 2). At no age is
DCIS more common than invasive breast cancer. Between the ages
of 40 and 64, between 21% and 22.8% of all breast cancers are
DCIS. Before age 40 and after age 64, the proportion of breast
cancers that are DCIS drops to as low as 9%. The change in inci-
dence of DCIS over time increases in all age groups but are the
greatest among women older than 50 years.
Ductal Carcinoma In Situ: Risk Factors and Impact of Screening
Beth A. Virnig, Shi-Yi Wang, Tatyana Shamilyan, Robert L. Kane, Todd M. Tuttle
Correspondence to: Beth A. Virnig, PhD, MPH, Division of Health Policy and Management, School of Public Health, University of Minnesota, A365 Mayo
(MMC 729), 420 Delaware St SE, Minneapolis, MN 55455 (e-mail: firstname.lastname@example.org).
Background The National Institutes of Health Office of Medical Applications of Research commissioned a structured litera-
ture review on the incidence of ductal carcinoma in situ (DCIS) as a background paper for the State of the
Science Conference on Diagnosis and Management of DCIS.
Methods Published studies were abstracted from MEDLINE and other sources. We include articles published through
January 31, 2009; 92 publications were abstracted.
Results DCIS incidence rose from 1.87 per 100 000 in 1973–1975 to 32.5 per 100 000 in 2005. Increases in incidence were
greatest in tumors without comedo necrosis. Incidence increased in all ages but more in women older than
50 years. Increased use of mammography explains some but not all of the increased incidence. Risk factors for
incident DCIS include older age and positive family history. Whereas tamoxifen prevents both invasive breast
cancer and DCIS, raloxifene is associated with decreased invasive breast cancer but not decreased DCIS.
Conclusions Scientific questions deserving further investigation include the relationship between mammography use and
DCIS incidence and the role of chemoprevention for reducing the incidence of DCIS and invasive breast
J Natl Cancer Inst Monogr 2010;41:113–116
by guest on August 24, 2015
114 Journal of the National Cancer Institute Monographs, No. 41, 2010
The age-adjusted incidence of DCIS was the highest among
Caucasian women followed by African American and Asian-Pacific
Islanders (3). Hispanic women had the lowest age-adjusted inci-
dence of DCIS. The lower rates of DCIS for African American,
Asian, and Hispanic women are coupled with lower rates of inva-
sive cancer. Thus, the evidence does not suggest that lower rates of
DCIS in nonwhites should be viewed as indicating a failure to
diagnose breast cancer early but could be related to lower underlying
risk of breast cancer.
Other DCIS Risk Factors
Several well-designed studies found that women who were older at
the time of first birth or had no children had a higher risk of devel-
oping DCIS than women who were younger. Similarly, studies
generally found that women who had more children had lower risk
of DCIS than women who had more (4,5).
The effect of oral contraceptive use and DCIS was examined in
five studies (6–10). No study found an association between ever use
of oral contraceptive (6–9) or past use (9) and DCIS incidence.
Neither of the studies evaluating duration of oral contraceptive use
found an association with DCIS incidence (8,9).
The association between hormone replacement therapy (HRT)
and DCIS was examined in both observational and randomized
studies. The five observational studies using varying definitions of
use were generally unable to distinguish between estrogen plus
progestin and estrogen alone. A large prospective cohort study
from the United Kingdom found a 56% increased risk of DCIS in
current users of HRT compared with never users (11). Other
US-based studies found that the increased risk of DCIS with HRT
varied with duration of use. Current users of HRT for less than
5 years compared with never users had statistically significantly
less risk of DCIS than nonusers (pooled relative risk [RR] = 0.78),
whereas current users of HRT for more than 5 years had greater
risk of DCIS compared with never users (pooled RR = 1.41)
(12,13). Two randomized trials of HRT using estrogen plus pro-
gestin failed to show any association between HRT and DCIS.
The Women’s Health Initiative found no increased risk of DCIS
associated with HRT (14). The Million Women Study cohort,
failed to comment on whether they observed any increase in DCIS
associated with HRT use.
Although a variety of definitions were used, studies consistently
found that increased breast density was associated with increased
risk of DCIS. For example, women with a mean breast density of
more than 45 cm2 also had greater odds of DCIS than women with
a low breast density of less than 15 cm2 (odds ratio [OR] 2.59, 95%
CI = 1.39 to 4.82) (15).
The association between body composition and body mass
index is mixed and not widely studied. For example, the Iowa
Women’s Health study did not find decreased risk of DCIS to be
Figure 2. Incidence of DCIS and invasive breast cancer by age (2002–
Figure 1. Trends in age-adjusted comedo and
non-comedo DCIS and invasive breast cancer
per 100 000 women (1,2).
19871988 1989199019911992 1993 19941995 19961997 19981999 2000 2001
Non Comedo DCIS Comedo DCIS Invasive breast cancer
by guest on August 24, 2015
Journal of the National Cancer Institute Monographs, No. 41, 2010 115
associated with body mass index. In contrast, Kerlikowske found
that heavily obese (body mass index ≥35.0 kg/m2) postmenopausal
women not taking HRT had increased odds ratio of DCIS (OR =
1.46) relative to normal weight women after adjustment for race,
ethnicity, age, mammography use, and registry (16).
Several studies reported that women with a family history of
breast cancer or a first-degree relative with breast cancer had simi-
larly increased odds ratio of DCIS compared with women without
a positive family history (pooled OR = 1.97, 95% CI = 1.10 to 3.52)
(eg, 5,6,8,17). Likewise, rates of DCIS have been found to be
higher among carriers of the BRCA1/2 gene mutation and among
those with estimated risk of breast cancer more than 25% (18). A
US-based cohort of similarly high-risk women found the cumula-
tive crude incidence of DCIS over 7 years to be 9.1% (95% CI =
2.3 to 30) (19).
Few studies have examined the association between DCIS inci-
dence and behavioral risk factors such as alcohol consumption,
smoking, aspirin and nonsteroidal anti-inflammatory drugs, physical
activity, dietary beta carotene intake.
Mammography and DCIS
The strongest evidence about the association between DCIS inci-
dence and use of screening mammography are from eight population-
based trials of mammography screening (20–27). Although all
trials found that mammographic screening was more likely to lead
to the diagnosis of invasive breast cancer than that of DCIS, no trial
found more than 20% of screen-detected breast cancers to be
DCIS. All but the National Breast Cancer Screening trials found
mammography to result in significant reductions in breast cancer
mortality (20,21). An analysis combining the Gothenburg Trial and
the Two-County Trial (28) compared the number of cases of DCIS
and invasive cancer in the screened population relative to the con-
trol. The authors estimated that 15% of DCIS cases in the Swedish
Two-County Trial and 18% of DCIS in the Gothenburg Trial
represent overdiagnosis and concluded that overdiagnosed DCIS
did not present a major clinical or public health problem.
The conclusions from the randomized trials are supported by a
number of population-based studies from the United States and
around the world. Namely, although mammography results in
increased detection of DCIS, the number of invasive cancers
always outnumbers DCIS cases. The effect of screening programs
on incidence of DCIS per 1000 screening mammograms was stud-
ied using data from the Breast Cancer Surveillance Consortium
and the National Breast and Cervical Cancer Early Detection
Program (29,30). In all age groups and overall, the incidence of
DCIS among screened women (0.78 per 10 000 women) was
greater than the incidence of DCIS among women who were not
screened (0.13 per 10 000 women). The incidence of DCIS
increased over time, even when the rate of mammography was
There is considerable evidence that the detection of DCIS is
greatest at baseline screening. An average annual incidence of
DCIS per 1000 screening mammograms was greater after the first
screening for women 50–59 and 70–84 years of age than for subse-
quent screens (29). Both screening and population-based studies
point to increased detection on baseline screening and decreased
rates of DCIS detection on follow-up screens. Though the differ-
ences are not large, they do suggest that the greatest increase in
incidence will be observed when a population undergoes initial
screening and that the increases in incidence based on this initial
screen will over estimate population impact for a population
undergoing routine screening.
Chemoprevention and Detection of DCIS
Several trials have assessed the value of tamoxifen or raloxifene for
preventing DCIS, although the trials, in reality, were designed to
assess the value of the agents for preventing breast cancer rather
than DCIS. The largest, the National Surgical Adjuvant Breast and
Bowel Project P-1 study (31) found statistically significant reduc-
tions in both DCIS and invasive breast cancer associated with
tamoxifen use among high-risk women. In the International Breast
Cancer Intervention Study, more than 7000 high-risk women
between the ages of 35 and 70 from the United Kingdom, Australia,
and New Zealand were randomized to tamoxifen, 20 mg/day for
5 years, or placebo (32). The tamoxifen group experienced a 69%
reduced incidence of DCIS at 50 months (RR = 0.31, 95% CI =
0.12 to 0.82), but the protective effect was not apparent by 4 years
after treatment stopped (study month 96), suggesting that the value
of tamoxifen for preventing DCIS may not be maintained after
treatment ceases. Although, the value of treatment for preventing
invasive disease was maintained (33).
The Study of Tamoxifen and Raloxifene trial randomized over
19 000 women to one of two therapies for preventing breast cancer.
Women in the tamoxifen group had half the incidence of in situ
breast cancer (lobular carcinoma in situ or DCIS) than women in the
raloxifene group (57 vs 81 in situ cancers). The study found that both
treatments reduced incidence of invasive breast cancer by half (34).
The Continuing Outcomes Relevant to Evista/Multiple
Outcomes of Raloxifene Evaluation randomized double-blind trial
examined the impact of raloxifene for preventing invasive breast
cancer among postmenopausal women with osteoporosis. The
study found statistically reduced incidence of invasive breast cancer
associated with raloxifene (HR = 0.50) but a nonsignificant
increase in the incidence of DCIS among the treated women
(HR = 1.78) (35).
There is ample evidence that the incidence of DCIS is increasing
and that the increases are largely due to increased use of screening
mammography. Several population-based trials along with other
population-based registries also support the conclusion that mam-
mography is more effective at identifying invasive breast cancer
than DCIS. We were unable to find any study that reported both
DCIS and invasive breast cancer that reported detecting more
DCIS than invasive breast cancer. Thus, although the increase
in DCIS is likely due to screening, the benefits of screening out-
weigh the increased detection of DCIS.
There is remarkable similarity in risk factors between DCIS
and invasive breast cancer with two notable exceptions—first, the
age pattern of DCIS and invasive breast cancer are somewhat dif-
ferent. DCIS peaks at a younger age than does invasive cancer.
Second, there is no evidence that HRT is associated with increases
in DCIS incidence as it is with invasive breast cancer. Other risk
by guest on August 24, 2015
116 Journal of the National Cancer Institute Monographs, No. 41, 2010
factors including breast density, family history, and history of
benign breast disease are similar between invasive cancer and
Trials of tamoxifen and raloxifene for breast cancer prevention
point to both drugs being effective for preventing invasive breast
cancer but tamoxifen being more effective for preventing DCIS.
Understanding this effect and how best to prevent all forms of
breast cancer deserves further attention.
1. Ries LaG, Melbert D, Krapcho M, et al. SEER Cancer Statistics Review,
1975–2005.Bethesda, MD: National Cancer Institute; 2008. http://seer.
cancer.gov/csr/1975_2005/. Accessed March 28, 2010.
2. Li CI, Daling JR, Malone KE. Age-specific incidence rates of in situ breast
carcinomas by histologic type, 1980 to 2001. Cancer Epidemiol Biomarkers
3. Innos K, Horn-Ross PL. Recent trends and racial/ethnic differences in the
incidence and treatment of ductal carcinoma in situ of the breast in
California women. Cancer. 2003;97(4):1099–1106.
4. Wohlfahrt J, Rank F, Kroman N, et al. A comparison of reproductive risk
factors for CIS lesions and invasive breast cancer. Int J Cancer. 2004;108(5):
5. Kerlikowske K, Barclay J, Grady D, et al. Comparison of risk factors for
ductal carcinoma in situ and invasive breast cancer. J Natl Cancer Inst.
6. Trentham-Dietz A, Newcomb PA, Storer BE, et al. Risk factors for carci-
noma in situ of the breast. Cancer Epidemiol Biomarkers Prev. 2000;9(7):
7. Vamre TB, Stalsberg H, Thomas DB. Extra-tumoral breast tissue in
breast cancer patients: variations with steroid contraceptive use. Int
J Cancer. 2006;118(11):2827–2831.
8. Claus EB, Stowe M, Carter D. Breast carcinoma in situ: risk factors and
screening patterns. J Natl Cancer Inst. 2001;93(23):1811–1817.
9. Bohlke K, Cramer DW, Trichopoulos D, et al. Insulin-like growth factor-I
in relation to premenopausal ductal carcinoma in situ of the breast.
10. Claus EB, Stowe M, Carter D. Oral contraceptives and the risk of ductal
breast carcinoma in situ. Breast Cancer Res Treat. 2003;81(2):129–136.
11. Reeves GK, Beral V, Green J, et al. Hormonal therapy for menopause and
breast-cancer risk by histological type: a cohort study and meta-analysis.
Lancet Oncol. 2006;7(11):910–918.
12. Gapstur SM, Morrow M, Sellers TA. Hormone replacement therapy and
risk of breast cancer with a favorable histology: results of the Iowa
Women’s Health Study. JAMA. 1999;281(22):2091–2097.
13. Kerlikowske K, Miglioretti DL, Ballard-Barbash R, et al. Prognostic char-
acteristics of breast cancer among postmenopausal hormone users in a
screened population. J Clin Oncol. 2003;21(23):4314–4321.
14. Chlebowski RT, Hendrix SL, Langer RD, et al. Influence of estrogen plus
progestin on breast cancer and mammography in healthy postmenopausal
women: the Women’s Health Initiative Randomized Trial. JAMA.
15. Gill JK, Maskarinec G, Pagano I, et al. The association of mammographic
density with ductal carcinoma in situ of the breast: the Multiethnic
Cohort. Breast Cancer Res. 2006;8(3):R30.
16. Kerlikowske K, Walker R, Miglioretti DL, et al. Obesity, mammography
use and accuracy, and advanced breast cancer risk. J Natl Cancer Inst.
17. Trentham-Dietz A, Newcomb PA, Storer BE, et al. Risk factors for carci-
noma in situ of the breast. Cancer Epidemiol Biomarkers Prev. 2000;9(7):
18. Brekelmans CT, Seynaeve C, Bartels CC, et al. Effectiveness of breast
cancer surveillance in BRCA1/2 gene mutation carriers and women with
high familial risk. J Clin Oncol. 2001;19(4):924–930.
19. Komenaka IK, Ditkoff BA, Joseph KA, et al. The development of interval
breast malignancies in patients with BRCA mutations. Cancer. 2004;
20. Miller AB, To T, Baines CJ, et al. Canadian National Breast Screening
Study-2: 13-year results of a randomized trial in women aged 50–59 years.
J Natl Cancer Inst. 2000;92(18):1490–1499.
21. Miller AB, To T, Baines CJ, et al. The Canadian National Breast
Screening Study-1: breast cancer mortality after 11 to 16 years of follow-
up. A randomized screening trial of mammography in women age 40 to 49
years. Ann Intern Med. 2002;137(5, pt 1):305–312.
22. Bjurstam N, Bjorneld L, Warwick J, et al. The Gothenburg Breast
Screening Trial. Cancer. 2003;97(10):2387–2396.
23. Shapiro S. Periodic screening for breast cancer: the HIP Randomized
Controlled Trial. Health Insurance Plan. J Natl Cancer Inst Monogr.
24. Nystrom L, Andersson I, Bjurstam N, et al. Long-term effects of mam-
mography screening: updated overview of the Swedish randomised trials.
25. Tabar L, Vitak B, Chen HH, et al. The Swedish Two-County Trial
twenty years later. Updated mortality results and new insights from long-
term follow-up. Radiol Clin North Am. 2000;38(4):625–651.
26. Roberts MM, Alexander FE, Anderson TJ, et al. The Edinburgh randomised
trial of screening for breast cancer: description of method. Br J Cancer.
27. Frisell J, Lidbrink E, Hellstrom L, et al. Followup after 11 years—update
of mortality results in the Stockholm mammographic screening trial.
Breast Cancer Res Treat. 1997;45(3):263–270.
28. Duffy SW, Agbaje O, Tabar L, et al. Overdiagnosis and overtreatment of
breast cancer: estimates of overdiagnosis from two trials of mammo-
graphic screening for breast cancer. Breast Cancer Res. 2005;7(6):258–265.
29. Ernster VL, Ballard-Barbash R, Barlow WE, et al. Detection of ductal
carcinoma in situ in women undergoing screening mammography. J Natl
Cancer Inst. 2002;94(20):1546–1554.
30. Smith-Bindman R, Chu PW, Miglioretti DL, et al. Comparison of screen-
ing mammography in the United States and the United Kingdom. JAMA.
31. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention
of breast cancer: report of the National Surgical Adjuvant Breast and
Bowel Project P-1 Study. J Natl Cancer Inst. 1998;90(18):1371–1388.
32. Cuzick J, Forbes J, Edwards R, et al. First results from the International
Breast Cancer Intervention Study (IBIS-I): a randomised prevention trial.
33. Cuzick J, Forbes JF, Sestak I, et al. Long-term results of tamoxifen pro-
phylaxis for breast cancer—96-month follow-up of the randomized IBIS-I
trial. J Natl Cancer Inst. 2007;99(4):272–282.
34. Vogel VG, Costantino JP, Wickerham DL, et al. Effects of tamoxifen vs
raloxifene on the risk of developing invasive breast cancer and other dis-
ease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR)
P-2 trial. JAMA. 2006;295(23):2727–2741.
35. Martino S, Cauley JA, Barrett-Connor E, et al. Continuing outcomes
relevant to Evista: breast cancer incidence in postmenopausal osteoporotic
women in a randomized trial of raloxifene. J Natl Cancer Inst. 2004;96(23):
Agency for Healthcare Research and Quality, U.S. Department of Health and
Human Services (290-02-10064-I).
The following is a summary of a report requested by the National Institutes of
Health Office of Medical Applications of Research as a background paper for
the State of the Science Conference on Diagnosis and Management of Ductal
Carcinoma In Situ (DCIS), a noninvasive form of breast cancer. The report is
available at http://www.ahrq.gov//clinic/epcix.htm.
Affiliations of authors: Division of Health Policy and Management, School
of Public Health (BAV, S-YW, TS, RLK), Masonic Cancer Center (BAV, TMT)
and Department of Surgery, School of Medicine, University of Minnesota,
Minneapolis, MN (TMT).
by guest on August 24, 2015