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Vol. 33, 2011
Advance Access publication:
June 22, 2011
Breast Cancer Screening: A 35-Year Perspective
Suzanne W. Fletcher*
* Correspondence to Dr. Suzanne W. Fletcher, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim
Health Care Institute, 133 Brookline Avenue, 6th Floor, Boston, MA 02215 (e-mail: firstname.lastname@example.org).
Accepted for publication January 31, 2011.
Screening for breast cancer has been evaluated by 9 randomized trials over 5 decades and recommended by
major guideline groups for more than 3 decades. Successes and lessons for cancer screening from this history
include development of scientific methods to evaluate screening, by the Canadian Task Force on the Periodic
Health Examination and the U.S. Preventive Services Task Force; the importance of randomized trials in the past,
and the increasing need to develop new methods to evaluate cancer screening in the future; the challenge of
assessing new technologies that are replacing originally evaluated screening tests; the need to measure false-
positive screening test results and the difficulty in reducing their frequency; the unexpected emergence of over-
diagnosis due to cancer screening; the difficulty in stratifying individuals according to breast cancer risk; women’s
fear of breast cancer and the public outrage over changing guidelines for breast cancer screening; the need for
population scientists to better communicate with the public if evidence-based recommendations are to be heeded
by clinicians, patients, and insurers; new developments in the primary prevention of cancers; and the interaction
between improved treatment and screening, which, over time, and together with primary prevention, may decrease
the need for cancer screening.
breast neoplasms; early detection of cancer
Abbreviation: USPSTF, U.S. Preventive Services Task Force.
My introduction to breast cancer began in 1962, during
the first week of medical school. Special grand rounds were
held for new students. Awoman with breast cancer (onewho
I now know had a tumor that was estrogen-receptor positive)
had been diagnosed many years before; she had been treated
sequentially with mastectomy, ovariectomy, adrenalectomy,
and pituitectomy. When first diagnosed, she wondered
whether she would live to see her son’s bar mitzvah; at
the rounds, she looked forward to his impending wedding.
The presentation taught students stages of breast cancer and
treatments. There was not a word about screening.
A year later, in 1963, the Health Insurance Plan of New
York, the first randomized trial of cancer screening, began
to evaluate mammography and clinical breast examination.
The trial, first results of which were reported in 1971 (1), set
the standard for conducting the 8 succeeding randomized
trials of breast cancer screening over the next 45 years.
Altogether, randomized trials of breast cancer screening
have involved more than 650,000 women. Screening for
no other cancer has received such intense study; even so,
no other cancer screening has produced such heated con-
troversy. Multiple reviews and conclusions have been pub-
lished, and interest has been strong not only in the medical
literature but also among the lay public.
This paper is not another review. Rather, I focus on the
larger lessons that research on breast cancer screening has
uncovered. Over the years, the scientific controversy has
spurred discoveryand new thinking as investigators explored
multiple ways of analyzing the accumulating data. This pro-
cess hasled tomanyof the lessonsI discuss. My professional
career serendipitously has spanned the period from pre–
breast cancer screening to the present time—giving me
a front-row seat to observe and a chance to participate (Table
1). Most of the lessons that emerged apply to not only breast
cancer but other cancers as well. Along the way, I suggest
some next steps that are needed. Finally, I consider possible
long-term future directions for cancer screening.
165Epidemiol Rev 2011;33:165–175
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THE CANADIAN TASK FORCE ON THE PERIODIC
The Canadian Task Force on the Periodic Health
Examination (now the Canadian Task Force on Preventive
Health Care) was established in 1976 (2), 5 years after
the first published results of the Health Insurance Plan of
New York trial. Formed at the request of the Conference
of Deputy Ministers of Health of Canada, the Task Force
evaluated the periodic health examination and made rec-
ommendations for office-based preventive practices. Its
report was to, not from, government. The 10 Task Force
members all came from academic settings, primarily clini-
cal departments. Several members were experts in clinical
epidemiology, epidemiology, and/or biostatistics.
From the perspective of 35 years, the importance of the
Task Force’s work lay not so much in its specific recommen-
dations as the approach it hammered out to evaluate evi-
dence about office-based preventive services. In doing so,
it examined previous recommendations and considerations,
particularly those of Frame and Carlson (3–6) and Sackett
and Holland (7). Most importantly, the Task Force based its
recommendations on evidence in the medical literature.
Fifty-seven of the 78 health conditions the Task Force
considered in depth involved screening (10 for cancer).
The Task Force defined screening as an activity in asymp-
tomatic persons ‘‘making use of procedures by which un-
selected general populations are classified into 2 groups: one
with a high probability of being affected by killing or dis-
abling conditions, unhealthy states or unhealthy behaviors,
and the other with a low probability’’ (8, p. 13). Screening
procedures included history-taking, physical examination,
laboratory testing, and procedures such as radiography.
The Task Force recommended replacing the untargeted
complete ‘‘annual examination’’ with a highly targeted ex-
amination aimed at preventing specific conditions, packaged
according to the age and sex of the patient. This approach
has now become the standard for preventive services, not
only in Canada and the United States but in many other
countries as well.
In deciding what conditions to target, the Task Force
formalized several important methodological contributions
to screening. First, when considering the evidence for
screening for a given condition, Task Force members
searched the health literature for answers to 3 questions,
an approach that still constitutes the bedrock for evaluating
screening (Table 2): 1) How great is the burden of suffering
caused by the condition being sought? 2) How good is the
test used to detect the condition during screening? and 3)
How effective is the resulting treatment or preventive
The second major contribution was the Task Force’s
approach to evidence. It recognized that evidence about
effectivenessof preventionvaried in terms of scientificrigor.
Evidence from a well-designed and conducted randomized
trial was given more weight in final recommendations
than evidence from a cohort study, which in turn was stron-
ger than the opinion of a clinical expert. The Task Force
formally incorporated the strength of evidence into its
recommendations by developing a grading system, from I
(evidence from at least one well-conducted randomized
trial) to III (expert testimony).
The third major contribution was to assign an overall
grade to the recommendation for screening each condition
considered. Grades ranged from A (good evidence that the
condition be specifically considered in a periodic health
examination) to C (not enough good evidence to recom-
mend whether to include or exclude the condition in a
periodic health examination) to E (good evidence to recom-
mend that the condition be excluded from the periodic
health examination). The graded recommendation was to
incorporate all the information uncovered about the 3 ques-
tions of effectiveness, burden, and test quality; however,
in practice, recommendations were dominated by strength
of the evidence about effectiveness of treatment or pre-
vention after screening. Table 3 shows the distribution of
recommendation grades. In several cases, the Task Force
indicated that screening should receive high priority for
THE U.S. PREVENTIVE SERVICES TASK FORCE
The U.S. Preventive Services Task Force (USPSTF), an
independent panel of experts in primary care, prevention,
and research methods, was begun in 1984. Supported since
1998 by the Agency for Healthcare Quality and Research,
it is charged by law to review the scientific evidence
and make recommendations for clinical preventive services
(9). Interaction with the Canadian Task Force has included
Table 1.Author’s Activities on Groups Evaluating Breast Cancer Screening
1976–1979 Canadian Task Force on the Periodic Health Examination (member)
1984–1988U.S. Preventive Services Task Force (member)
1993National Cancer Institute International Workshop on Screening
for Breast Cancer (chair)
1997 National Institutes of Health Consensus-Development Conference on
Breast Cancer Screening for Women Ages 40–49 (presenter)
2002International Agency for Research on Cancer Working Group on the
Evaluation of Cancer-Preventive Strategies: Breast Cancer Screening (member)
2002 Institute of Medicine Committee on Technologies for the Early Detection of Breast Cancer (member)
Epidemiol Rev 2011;33:165–175
by guest on October 29, 2015
40. Barton MB, Morley DS, Moore S, et al. Decreasing women’s
anxieties after abnormal mammograms: a controlled trial.
J Natl Cancer Inst. 2004;96(7):529–538.
41. Altekruse SF, Kosary CL, Krapcho M, et al, eds. SEER
cancer statistics review, 1975–2007. Bethesda, MD:
National Cancer Institute; 2010. (http://seer.cancer.gov/csr/
1975_2007/). (Accessed November 18, 2010).
42. Biesheuvel C, Barratt A, Howard K, et al. Effects of study
methods and biases on estimates of invasive breast cancer
overdetection with mammography screening: a systematic
review. Lancet Oncol. 2007;8(12):1129–1138.
43. Zackrisson S, Andersson I, Janzon L, et al. Rate of
over-diagnosis of breast cancer 15 years after end of Malmo ¨
mammographic screening trial: follow-up study. BMJ.
44. Welch HG, Schwartz LM, Woloshin S. Ramifications of
screening for breast cancer: 1 in 4 cancers detected by
mammography are pseudocancers [letter]. BMJ. 2006;
45. Allegra CJ, Aberle DR, Ganschow P, et al. National Institutes
of Health State-of-the-Science Conference statement:
Diagnosis and management of ductal carcinoma in situ,
September 22–24, 2009. J Natl Cancer Inst. 2010;102(3):
46. Draisma G, Etzioni R, Tsodikov A, et al. Lead time and
overdiagnosis in prostate-specific antigen screening:
importance of methods and context. J Natl Cancer Inst.
47. Barry MJ, Mulley AJ. Why are a high overdiagnosis
probability and a long lead time for prostate cancer
screening so important? J Natl Cancer Inst. 2009;101(6):
48. Institute of Medicine and National Research Council. Saving
Women’ s Lives: Strategies for Improving Breast Cancer
Detection and Diagnosis. Washington, DC: National Academy
49. Kerlikowske K. Evidence-based breast cancer prevention:
the importance of individual risk. Ann Intern Med. 2009;
50. National Cancer Institute. Breast cancer risk assessment
tool: an interactive tool to help estimate a woman’s risk of
developing breast cancer. Bethesda, MD: National Cancer
Institute, National Institutes of Health; 2008. (http://www.
cancer.gov/bcrisktool/). (Accessed November 18, 2010).
51. Elmore JG, Fletcher SW. The risk of cancer risk prediction:
"What is my risk of getting breast cancer?" J Natl Cancer Inst.
52. Wacholder S, Hartge P, Prentice R, et al. Performance of
common genetic variants in breast-cancer risk models.
N Engl J Med. 2010;362(1):986–993.
53. Rose G. Sickindividuals andsick populations. Int J Epidemiol.
54. Wald NJ, Hackshaw AK, Frost CD. When can a risk factor
be used as a worthwhile screening test? BMJ. 1999;319(7224):
55. Mandelblatt JS, Cronin KA, Bailey S, et al. Effects of
mammography screening under different screening schedules:
model estimates of potential benefits and harms. Ann Intern
56. Fletcher SW, Spitzer WO. Approach of the Canadian Task
Force to the periodic health examination. Ann Intern Med.
1980;92(2 pt 1):253–254.
57. U.S. Department of Health and Human Services, Public
Health Service, Office of Disease Prevention and Health
Promotion. Clinician’s Handbook of Preventive Services: Put
Prevention Into Practice. Washington, DC: US Government
Printing Office; 1994.
58. Fletcher SW. Whither scientific deliberation in health policy
recommendations? Alice in the Wonderland of breast-cancer
screening. N Engl J Med. 1997;336(16):1180–1183.
59. Mathews J. Bad science in the Senate. Washington Post.
February 10, 1997:A19.
60. Yalom M. A History of the Breast. New York, NY: Ballantine
61. Fletcher SW, Black W, Harris R, et al. Report of The
International Workshop on Screening for Breast Cancer. J Natl
Cancer Inst. 1993;85(20):1644–1656.
62. Kolata G. Studies say mammograms fail to help many women.
New York Times. February 26, 1993:A1.
63. Rimer BK, Briss PA, Zeller PK, et al. Informed decision
making: what is its role in cancer screening? Cancer. 2004;
preferences of women in their 40s before their first screening
mammogram. Arch Intern Med. 2005;165(12):1370–1374.
65. Fletcher SW, Elmore JG. Clinical practice. Mammographic
screening for breast cancer. N Engl J Med. 2003;348(17):
66. Nekhlyudov L, Braddock CH III. An approach to enhance
communication about screening mammography in primary
care. J Womens Health (Larchmt). 2009;18(9):1403–1412.
67. O’Connor AM, Bennett CL, Stacey D, et al. Decision aids
for people facing health treatment or screening decisions.
Cochrane Database Syst Rev. 2009(3):CD001431.
68. Kolata G. Stand on mammograms greeted by outrage. New
York Times. January 28, 1997:C1, C8.
69. Rabin RC. New guidelines on breast cancer draw opposition.
New York Times. November 17, 2009:D5.
70. Woolf SH. The 2009 breast cancer screening recommen-
dations of the US Preventive Services Task Force. JAMA.
71. Biggs ML, Schwartz SM. Cancer of the testis. In: Ries LAG,
Young JL, Keel GE, et al, eds. SEER Survival Monograph:
Cancer Survival Among Adults: U.S. SEER Program,
1988–2001, Patient and Tumor Characteristics. Chapter 12.
Bethesda, MD: National Cancer Institute, SEER Program;
2007. (NIH publication no. 07-6215).
72. U.S. Preventive Services Task Force. Screening for testicular
cancer: U.S. Preventive Services Task Force reaffirmation
recommendation statement. Ann Intern Med. 2011;154(7):
73. Berry DA, Cronin KA, Plevritis SK, et al. Effect of
screening and adjuvant therapy on mortality from breast
cancer. N Engl J Med. 2005;353(17):1784–1792.
74. Kalager M, Zelen M, Langmark F, et al. Effect of screening
mammography on breast-cancer mortality in Norway.
N Engl J Med. 2010;363(13):1203–1210.
75. Moss SM, Cuckle H, Evans A, et al. Effect of mammo-
graphic screening from age 40 years on breast cancer mortality
at 10 years’ follow-up: a randomised controlled trial. Lancet.
76. Elmore JG, Reisch LM, Barton MB, et al. Efficacy of breast
cancer screening in the community according to risk level.
J Natl Cancer Inst. 2005;97(14):1035–1043.
77. Welch HG. Screening mammography—a long run for
a short slide? N Engl J Med. 2010;363(13):1276–1278.
78. U.S. Preventive Services Task Force. Screening for breast
cancer: U.S. Preventive Services Task Force recommendation
statement. Ann Intern Med. 2009;151(10):716–726.
Breast Cancer Screening: A 35-Year Perspective175
Epidemiol Rev 2011;33:165–175
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