Download full-text PDF

Overdiagnosis and overtreatment of breast cancer: Rates of ductal carcinoma in situ: a US perspective

Article (PDF Available) inBreast cancer research: BCR 7(6):271-5 · February 2005with30 Reads
DOI: 10.1186/bcr1346 · Source: PubMed
Abstract
The incidence of breast ductal carcinoma in situ (DCIS) in the USA exceeds that of other countries. This cannot be explained entirely by the frequency of mammographic screening in the USA and may result from differences in the interpretation of mammograms and/or the frequency with which biopsies are obtained. Although the percentage of DCIS patients treated with mastectomy has decreased, the absolute number is unchanged and the use of lumpectomy with whole-breast radiotherapy has increased in inverse proportion to the decrease in mastectomy. Treatment of DCIS with tamoxifen is still limited.
Figures
271
DCIS = ductal carcinoma in situ; NCCN = National Comprehensive Cancer Network; SEER = Surveillance, Epidemiology, and End Results.
Available online http://breast-cancer-research.com/content/7/6/271
Abstract
The incidence of breast ductal carcinoma in situ (DCIS) in the
USA exceeds that of other countries. This cannot be explained
entirely by the frequency of mammographic screening in the USA
and may result from differences in the interpretation of
mammograms and/or the frequency with which biopsies are
obtained. Although the percentage of DCIS patients treated with
mastectomy has decreased, the absolute number is unchanged
and the use of lumpectomy with whole-breast radiotherapy has
increased in inverse proportion to the decrease in mastectomy.
Treatment of DCIS with tamoxifen is still limited.
Introduction
The incidence of breast ductal carcinoma in situ (DCIS) has
increased steadily in all countries as the use of screening
mammography has increased [1]. In the USA the incidence of
DCIS remained below 5 per 100,000 and DCIS constituted
2.8 to 3.8% of breast cancers diagnosed between 1973 and
1984 [2]. It now exceeds 30 per 100,000 and constitutes
18.6% [3]. During this time the percentage of American
women aged 50 years and over who reported having a recent
mammogram increased from 27% in 1987 to 69% in 1998
[4]. Cancers detected by screening are more likely to be
DCIS, ranging from 18 to 33% in various studies [5].
DCIS with comedo histology is one of the subtypes most
likely to recur with an invasive histology [6]. From 1992 to
1999, when the overall incidence of DCIS in the USA
increased by 73%, there was no increase in the incidence of
comedo histology [7,8]. Several explanations have been
suggested for this, the most plausible being that DCIS found
in women undergoing screening mammography is more likely
to be the non-comedo variety [7].
Although the correlation between increased DCIS with
increased use of mammography seems to be universal, the
frequency of DCIS is still higher in the USA than in other
countries with similar mammography use (Table 1). The
incidence of carcinoma in situ (ductal plus lobular) had
increased in the USA, England and Switzerland by 1990
[8-10]. However, DCIS incidence in the USA was about
thrice that in England and Switzerland. For the early dates,
mammography rates might account for the difference in the
incidence of DCIS between America and Europe. That is less
true today.
Mammographic screening in the USA and the
UK today
Recommendations for screening in the USA and UK are quite
different. In the USA there is no national policy, but most
organizations, such as the American Cancer Society,
recommend mammograms every 1 or 2 years for women
more than 50 years old and many recommend initiating yearly
mammograms at the age of 40 years [11]. In the UK, it is
national policy to obtain mammograms every 3 years for
women aged 50 to 64 years but none for those less than
50 years old [12]. Today the reported rates of mammographic
screening in the two countries are similar for women aged 50
to 64 years. According to the 2002 National Health Interview
Survey, 78.6% of American women in this age group had a
mammogram within the previous 2 years. Similarly, 74.5% of
British women aged 53 to 64 years had been screened at
least once in the 3 years before 2004 [12]. For women less
than 50 years old, 33% of American women received a
mammogram in 1998 compared with only 2% in the UK in
2004. After the age of 65 years, the frequency of screening
declined abruptly in the UK before 2004, whereas one-third
of all mammograms were performed on American women in
this age group [12,13]. Although the ratio of DCIS/breast
cancer detected by screening mammography is highest in
women aged 40 to 49 years, the highest frequency of DCIS
per 1,000 mammograms is in the women aged 70 to
84 years [5]. Finally, there may be differences in the
socioeconomic status of the screened population in the two
Review
Overdiagnosis and overtreatment of breast cancer
Rates of ductal carcinoma
in situ
: a US perspective
Anjali S Kumar, Vinona Bhatia and I Craig Henderson
University of California, 1600 Divisadero Street, San Francisco, CA 94115, USA
Corresponding author: I Craig Henderson, chenderson@keryx.com
Published: 11 November 2005 Breast Cancer Research 2005, 7:271-275 (DOI 10.1186/bcr1346)
This article is online at http://breast-cancer-research.com/content/7/6/271
© 2005 BioMed Central Ltd
272
Breast Cancer Research December 2005 Vol 7 No 6 Kumar et al.
countries because mammograms are free in the UK but not in
the USA. Thus differences in screening patterns could
account for some of the international differences in DCIS
incidence.
Mammographic interpretation in the USA
versus other countries
There is considerable difference in the interpretation and
management of abnormal mammograms in different
countries. In a comparison of procedures and outcomes after
1.6 million mammograms in the USA and 3.9 million in the UK
between 1996 and 1999, it was found that recall rates per
100 mammograms were 13.4 in the USA versus 7.1 in the
UK, open biopsies 1.1 versus 0.7, and open negative
biopsies 0.8 versus 0.4. Despite these roughly doubled rates
in the USA, there were no differences in the overall cancer
detection rate [14]. Perhaps the greater use of open biopsy
results in a higher frequency of DCIS because it is often
diagnosed incidentally without radiographic findings.
A study that compared variability in mammographic
interpretation in 32 reports from community-based screening
programs in the USA and eight other countries found that
8.4% of mammograms were judged abnormal in North
America versus 5.6% in other countries (P = 0.018) [15].
Abnormal mammograms exceeded 5% in all of the North
American programs but in only 10 of the 24 programs
elsewhere. DCIS constituted more than 20% of the cancers
diagnosed in 4 of the 8 North American programs but in only
4 of the 24 programs elsewhere. There was a significant
correlation between the frequency of abnormal mammograms
and the percentage of cancers that were DCIS. Factors
affecting differences in outcome were the inclusion of
younger women with dense breasts, litigation avoidance, and
incentives to minimize the number of abnormal mammograms.
In the USA, the Agency for Health Care Policy and Research
suggests that at most 10% of mammograms should be
abnormal and 25 to 40% of biopsies should be positive. In
the Europe Against Cancer Program the ‘acceptable’ rate
and the ‘desirable levels’ of abnormal mammograms are less
than 7% and less than 5%, respectively, and the
corresponding levels for positive biopsies are more than 34%
and more than 50%.
Treatment of DCIS
For most of the twentieth century, treatment for DCIS was
mastectomy (Fig. 1). Even with the demonstration that
lumpectomy and radiotherapy were equally effective for
invasive cancer, reluctance to apply this principle to the
treatment of DCIS resulted in a very slow decline in
mastectomy rates among DCIS patients after 1979. In 2002,
26% of DCIS patients were still treated with mastectomy.
During the 1990s, the incidence of DCIS rose while
mastectomy rates decreased. As a result the age-adjusted
incidence of mastectomy did not change: 7.8 per 100,000
women in 1992 and 1999 [7]. Those most likely to undergo
mastectomy were younger patients and those with tumors
more than 1 cm in size or with comedo histology [7]. As
mastectomy rates have declined, there has been a gradual
increase lumpectomy rates to 71% in 2002.
In the USA most professional organizations have few, if any,
specific recommendations about the management of DCIS,
but the National Comprehensive Cancer Network (NCCN)
guidelines outlined in Fig. 2 are referred to by many of these
groups. Mastectomy is recommended in the presence of
diffuse, multifocal DCIS, or when all disease cannot be
removed with clear surgical margins after an excisional
biopsy. It is likely that many of the 26% of patients treated
with mastectomy do not meet these criteria. Axillary lymph
node dissection is discouraged unless areas of microinvasion
are found on pathology review, and this is reflected in the
steady decrease in lymphadenectomy since 1988 (Fig. 1). In
2002 only 11% of patients had a formal node dissection, and
10% had a sentinel node biopsy.
Radiotherapy is recommended for most patients treated with
excision, and in practice there has been a steady increase in
the use of radiotherapy since the early 1980s. The increased
use of radiotherapy antedated the 1993 report from the first
randomized trial evaluating radiotherapy for DCIS [16]. In
2002, more than 40% of all patients with DCIS received
Table 1
Changes in age-adjusted incident rates of DCIS and/or CIS
between 1980–2002
USA [8] England [9] Switzerland [10]
Year DCIS
a
CIS
b
DCIS
c
CIS
c
1980 4.0
1980–82 2.4 4.8
1983 5.0
1983–85 1.8 3.6
1984 7.8
1986–88 3.2 5.2
1989–91 7.3 10.6
1992 23.8 6.5
1992–94 7.9 10.4
1995 28.8 6.8
1998 38.0 9.4
1999 10.5
2001 37.8 11.6
2002 12.0
a
Adjusted to US population in 2000;
b
adjusted to European standard
population;
c
adjusted to population in US 1970 census. CIS,
carcinoma in situ; DCIS, ductal carcinoma in situ.
273
radiotherapy. The largest cancer registry in the USA, SEER
(Surveillance, Epidemiology, and End Results) did not link
radiotherapy to a specific surgical procedure, but it is likely
that most of the patients given radiotherapy had lumpectomy
rather than mastectomy. From this we estimate that 64% of
patients treated with lumpectomy also had radiotherapy.
Excision without radiotherapy is offered to patients with small
tumors and low-grade, non-comedo histology, but it is not
formally ‘recommended’ in the NCCN criteria, which define
‘small’ as ‘0.5 cm or less’. Some American DCIS specialists
feel comfortable using excision alone with lesions 2.5 cm in
size or smaller regardless of tumor grade if the margins are
more than 10 mm [17]. In practice, about 36% of patients
with DCIS seem to be treated with lumpectomy alone (Fig. 1).
Excision alone without radiotherapy is more likely to be
employed for those aged more than 50 years [7].
In a survey, North America radiotherapists (n = 1,137) were
more likely than European radiotherapists (n = 702) to
recommend radiotherapy for DCIS, but the differences were
greater among community than academic radiotherapists
[18]. For example, when asked about treatment of a grade I to
II, less than 2.5 cm DCIS lesion with a margin more than
10 mm, 53% of the academic and 28% of the community
radiotherapists in North American indicated that they would
not use radiotherapy, whereas 55% of the academic and
60% of the community radiotherapists in Europe
recommended no radiotherapy for this lesion.
Although the first randomized clinical trial that demonstrated
a beneficial effect from tamoxifen for DCIS appeared in 1999
[19], there is still considerable reluctance to employ this
treatment routinely. The NCCN recommends that physicians
‘consider’ tamoxifen for DCIS regardless of the primary
treatment or tumor characteristics (Fig. 2). There are no data
available from SEER on the use of tamoxifen for DCIS, but its
use in this setting has been reported from several cancer
centers. In a retrospective evaluation of 277 DCIS patients at
MD Anderson Cancer Center between 1999 and 2002, 60%
were offered tamoxifen; 54% of those offered accepted the
recommendation [20]. There was no change in the frequency
with which tamoxifen was offered between 1999 and 2002.
The most common reason that physicians did not recommend
tamoxifen was that the patient’s primary treatment was
mastectomy. The most common reason that patients declined
tamoxifen was fear of the side effects. Of those given
tamoxifen, 21% discontinued the medication because of side
Available online http://breast-cancer-research.com/content/7/6/271
Figure 1
Treatment of DCIS in the USA, 1973 to 2002. Source: SEER (Surveillance, Epidemiology, and End Results). These data were compiled at the
Northern California Cancer Center from Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) SEER*Stat
Database: Incidence – SEER 9 Regs Public-Use, Nov 2004 Sub (1973-2002), National Cancer Institute, DCCPS, Surveillance Research
Program, Cancer Statistics Branch, released April 2005, based on the November 2004 submission, which is a sum of data from population-based
cancer registries at nine distinct geographic sites collected for the period 1 January 1973 to 31 December 2002. The query was limited to women
with non-invasive in situ breast cancer, excluding lobular carcinoma in situ. Rates were age-adjusted with US census data from 2000. Patients with
any evidence of microinvasive disease would be considered by SEER to have invasive breast cancer and thus were excluded from the study. For
this time interval 45,597 cases met this definition, 189 cases in 1973 and 3,335 in 2002. The distribution of patients by type of surgery or use of
radiotherapy is based on the patients for whom there is a specific indication that the therapy was given or not given. The denominator for analyses
of other therapies is based on the total number of patients diagnosed. The number of patients included in the calculation for ‘lumpectomy’ includes
those who had a single surgical procedure and those who had an initial surgical procedure plus a re-excision. A few patients in the latter category
might have been counted twice if the two procedures were performed in different years. XRT, radiotherapy.
274
effects or complications. Thus, only 27% of this sample
completed a 5-year course of tamoxifen when it was offered.
In the international survey of radiotherapists described above,
North Americans were more likely to recommend tamoxifen
as well as radiotherapy [18]. For example, 74% of academic
and 76% of community-based radiotherapists in North
America recommended tamoxifen for a DCIS of less than
2.5 cm with grade 3 histology and margins of 1 to 3 mm
compared with 39% of academic 49% of community-based
radiotherapists in Europe who made this recommendation.
On both sides of the Atlantic, radiotherapists were more likely
to recommend tamoxifen for tumors of higher grade or
narrower margins.
Is DCIS overdiagnosed and overtreated in the
USA?
DCIS is diagnosed more frequently and treated more
aggressively in the USA than elsewhere. It is plausible that
differences in the incidence of DCIS in countries where
routine screening mammography is well established are
related as much to frequency of biopsies for suspicious
lesions as to the frequency of mammography.
The question of whether DCIS is diagnosed too frequently or
treated too aggressively in America depends on whether
these practices result in better outcomes. The outcome of
greatest interest, of course, is breast cancer mortality, but
because the reported incidence of death from breast cancer
in patients diagnosed with DCIS is somewhat less than 2%,
it will be difficult to detect differences between large
populations in which there are multiple variables in addition
to the method of diagnosis and treatment that might account
for any observed small differences. This problem is evident in
the comparison of mortality in patients diagnosed with DCIS
during two periods in the USA [2]. Among women in SEER
who were diagnosed with DCIS from 1978 to 1983,
mortality from breast cancer was 1.5 at 5 years and 3.4 at
10 years. For the interval 1984 to 1989 these rates were 0.7
and 1.9, respectively. In the later period, the use of
mammography increased rapidly and mastectomy for DCIS
decreased. Was mammography improving the prognosis of
patients with DCIS because of ‘earlier’ detection, or were
more cases of DCIS with low malignant potential being
diagnosed, thus exaggerating the apparent survival benefit?
This cannot be determined. On a more positive note,
outcomes that affect quality of life, such as the use of breast-
conserving surgery without axillary lymph node dissection,
are clearly improving.
Conclusion
Although one might conclude that the aggressiveness of
treatment decreased in the 1980s in the USA as a result of
decreased mastectomy rates, the opposite can be said of the
period after 1991, first with increasing use of radiotherapy
and now tamoxifen. There is reason to believe that physicians
are becoming more selective in their use of therapies.
Comedo DCIS has remained relatively constant in the face of
an overall increase in DCIS, and as of 1999, 33% of patients
with comedo carcinomas did not receive radiotherapy [7].
However, the survey of radiotherapists suggests that, at least
among American academic physicians, radiotherapy is limited
more and more to this group of patients [18]. Tamoxifen for
DCIS has not been as widely and quickly embraced as
radiotherapy was a decade ago. It is plausible that as more
information is generated on the natural history of DCIS,
practice patterns in the USA will once again change. It is less
certain that the incidence of DCIS will decrease.
Breast Cancer Research December 2005 Vol 7 No 6 Kumar et al.
Figure 2
Recommended management guidelines for DCIS developed by and subscribed to by American breast cancer specialists. The scheme shown here
is based primarily on guidelines developed by the National Comprehensive Cancer Network (NCCN), a coalition of 19 academic cancer centers in
the USA. The American College of Surgeons Commission on Cancer, the American Society of Clinical Oncologists, and the American Society for
Therapeutic Radiation Oncologists do not at present endorse any specific guidelines for the management of DCIS but refer to those of the NCCN
(Clinical Practice Guidelines in Oncology, Breast Cancer, V.2.2005: Ductal Carcinoma in Situ, DCIS-1 to 3) in their literature (or where information
is provided on the Internet, link to the NCCN site [21]). ALND, axillary lymph node dissection; ER, estrogen receptor; XRT, radiotherapy.
275
Competing interests
ICH has received reimbursements, fees, funding or salary
from AstraZeneca in the past five years.
References
1. Recht A, Rutgers EJ, Fentiman IS, Kurtz JM, Mansel RE, Sloane
JP: The fourth EORTC DCIS Consensus meeting (Chateau
Marquette, Heemskerk, The Netherlands, 23–24 January
1998) – conference report. Eur J Cancer 1998, 34:1664-1669.
2. Ernster VL, Barclay J, Kerlikowske K, Wilkie H, Ballard-Barbash R:
Mortality among women with ductal carcinoma in situ of the
breast in the population-based surveillance, epidemiology
and end results program. Arch Intern Med 2000, 160:953-958.
3. Ries LAG, Eisner MP, Kosary CL, Hankey BF, Miller BA, Clegg L,
Mariotto A, Feuer EJ, Edwards BK (eds): SEER Cancer Statistics
Review, 1975–2002. Bethesda, MD: National Cancer Institute;
http://seer.cancer.gov/csr/1975_2002/, based on November
2004 SEER data submission, posted to the SEER web site 2005.
4. Committee on Technologies for the Early Detection of Breast
Cancer, Nass SJ, Henderson IC, Lashof JC (eds): Mammography
and Beyond: Developing Technologies for the Early Detection of
Breast Cancer. National Cancer Policy Board, Institute of Medi-
cine, Division of Earth and Life Studies, National Research
Council: Washington DC; 2001.
5. Ernster VL, Ballard-Barbash R, Barlow WE, Zheng Y, Weaver DL,
Cutter G, Yankaskas BC, Rosenberg R, Carney PA, Kerlikowske
K, et al.: Detection of ductal carcinoma in situ in women
undergoing screening mammography. J Natl Cancer Inst
2002, 94:1546-1554.
6. Fisher ER, Dignam J, Tan-Chiu E, Costantino J, Fisher B, Paik S,
Wolmark N: Pathologic findings from the National Surgical
Adjuvant Breast Project (NSABP) eight-year update of Proto-
col B-17: intraductal carcinoma. Cancer 1999, 86:429-438.
7. Baxter NN, Virnig BA, Durham SB, Tuttle TM: Trends in the treat-
ment of ductal carcinoma in situ of the breast. J Natl Cancer
Inst 2004, 96:443-448.
8. Li CI, Daling JR, Malone KE: Age-specific incidence rates of in
situ breast carcinomas by histologic type, 1980 to 2001.
Cancer Epidemiol Biomarkers Prev 2005, 14:1008-1011.
9. N Cooper, M Gautrey, M Quinn: Cancer Trends in England and
Wales, Incidence Data to 2002. National Cancer Intelligence
Centre, Office for National Statistics; 2005. [http://www.statistics.
gov.uk/statbase/Expodata/Spreadsheets/D8981.xls]
10. Levi F, Te VC, Randimbison L, La Vecchia C: Trends of in situ
carcinoma of the breast in Vaud, Switzerland. Eur J Cancer
1997, 33:903-906.
11. US Preventive Services Task Force: Screening for breast
cancer: recommendations and rationale. Ann Intern Med 2002,
137:344-346.
12. Breast Screening Programme, England: 2003–2004
[http://www.dh.gov.uk/PublicationsAndStatistics/Statistics/
StatisticalWorkAreas/StatisticalHealthCare/
StatisticalHealthCareArticle/fs/en?CONTENT_ID=4104034&chk
=mjJ%2Bof]
13. Center for Disease Control: National Center for Health Statistics,
United States 2004. [http://www.cdc.gov/nchs/fastats/lifexpec.htm]
14. Smith-Bindman R, Chu PW, Miglioretti DL, Sickles EA, Blanks R,
Ballard-Barbash R, Bobo JK, Lee NC, Wallis MG, Patnick J, et al.:
Comparison of screening mammography in the United States
and the United Kingdom. JAMA 2003, 290:2129-2137.
15. Elmore JG, Nakano CY, Koepsell TD, Desnick LM, D’Orsi CJ, Ran-
sohoff DF: International variation in screening mammography
interpretations in community-based programs. J Natl Cancer
Inst 2003, 95:1384-1393.
16. Fisher B, Costantino J, Redmond C, Fisher E, Margolese R, Dim-
itrov N, Wolmark N, Wickerham L, Deutsch M, Ore L, et al.:
Lumpectomy compared with lumpectomy and radiation
therapy for the treatment of intraductal breast cancer. N Eng J
Med 1993, 328:1581-1586.
17. Silverstein MJ, Lagios MD, Groshen S, Waisman JR, Lewinsky
BS, Martino S, Gamagami P, Colburn WJ: The influence of
margin width on local control of ductal carcinoma in situ of
the breast. N Engl J Med 1999, 340:1455-1461.
18. Ceilley E, Jagsi R, Goldberg S, Kachnic L, Powell S, Taghian A:
The management of ductal carcinoma in situ in North America
and Europe. Results of a survey. Cancer 2004, 101:1958-
1967.
19. Fisher B, Dignam J, Wolmark N, Wickerham DL, Fisher ER,
Mamounas E, Smith R, Begovic M, Dimitrov NV, Margolese RG, et
al.: Tamoxifen in treatment of intraductal breast cancer:
National Surgical Adjuvant Breast and Bowel Project B-24
randomised controlled trial. Lancet 1999, 353:1993-2000.
20. Yen TW, Hunt KK, Mirza NQ, Thomas ES, Singletary SE, Babiera
GV, Meric-Bernstam F, Buchholz TA, Feig BW, Ross MI, et al.:
Physician recommendations regarding tamoxifen and patient
utilization of tamoxifen after surgery for ductal carcinoma in
situ. Cancer 2004, 100:942-949.
21. NCCN Clinical Practice Guidelines in Oncology – v.2.2005 –
Breast Cancer [http://www.nccn.org/professionals/physician_gls/
PDF/breast.pdf]
Available online http://breast-cancer-research.com/content/7/6/271
This article is part of a review series on
Overdiagnosis and overtreatment of breast cancer,
edited by Nick E Day, Stephen Duffy and Eugenio Paci.
Other articles in the series can be found online at
http://breast-cancer-research.com/articles/
review-series.asp?series=BCR_Overdiagnosis
Article
April 2001 · European Journal of Surgical Oncology · Impact Factor: 3.01
    To evaluate the diagnostic and therapeutic procedures which were followed in a European Organization for Research and Treatment of Cancer (EORTC) randomized clinical trial investigating the role of radiotherapy in breast-conserving treatment (BCT) for ductal carcinoma in situ (DCIS) of the breast. The medical files of 824 of the 1010 randomized patients (82%) were reviewed during site visits... [Show full abstract]
    Article
    August 2003 · The Lancet · Impact Factor: 45.22
      As a consequence of mammographic breast screening programmes, ductal carcinoma in situ is diagnosed with increasing frequency. Mastectomy for localised ductal carcinoma in situ is thought to be an over-treatment by many physicians, but there is much controversy as to whether complete local excision alone is sufficient. We aimed to assess the effectiveness of adjuvant radiotherapy and... [Show full abstract]
      Article
      March 2000 · The Lancet · Impact Factor: 45.22
        Ductal carcinoma in situ (DCIS) of the breast is a disorder that has become more common since it may manifest as microcalcifications that can be detected by screening mammography. Since selected women with invasive cancer can be treated safely with breast conservation therapy it is paradoxical that total mastectomy has remained the standard treatment for DCIS. We did a randomised phase III... [Show full abstract]
        Article
        March 2003 · Breast Cancer Research and Treatment · Impact Factor: 3.94
          To assess how women with ductal carcinoma in situ (DCIS) perceive their risks of recurrence, dying from breast cancer, and psychological distress compared to women with early stage invasive breast cancer (EIBC). Eligible patients included those with DCIS or EIBC (T1 or T2, N0) referred to one cancer center between November 1998 and June 1999. Participants completed a self-administered survey... [Show full abstract]
          Discover more