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Breast Cancer
Michael Douek his is the first article of a series on skin cancer. Each year, over 42,000
Department of Surgery,
Royal Free and University College Medical
T breast cancer. Each article will
cover an important aspect in the diag-
new cases are newly diagnosed and
12,400 women die from breast cancer.
School, London, UK.
nosis or treatment of breast cancer Men can also get breast cancer but it
Michael Douek is a Senior Lecturer and
Consultant Surgeon at University College focusing on recent advances and cur- is rare (300 cases each year in the UK).
London Hospitals focusing on breast cancer rent updates. This article is on breast There have been significant
surgery (including intra-operative radiother-
apy, sentinel node biopsy and reconstruc- screening which is now provided as a improvements in earlier detection and
tion) with a particular interest in pre-operative surgical planning routine service in several countries. in treatment of breast cancer. Largely
using breast MRI. His translational research program evaluates
novel imaging modalities to improve breast conserving surgery
The next few issues will cover breast as a result of advances in treatment, in
for cancer. He is a regular speaker at national and international imaging, surgical management, the UK breast cancer death rates have
conferences, published several papers in this area and made con- endocrine treatment, chemotherapy fallen by a fifth over the last ten years.
tributions in the health media.
and radiotherapy. Modern treatment is delivered by a
Michael graduated from the University of Dundee (Scotland) and Breast cancer is an enigmatic dis- multidisciplinary team including sur-
trained in surgery in London, Oxford and Cambridge. He obtained
his MD from the University of London in 2000. In 2003, he was ease with an unpredictable natural geons, oncologists, histopathologists,
awarded a prestigious Health Foundation Clinician Scientist grant history. In the UK, it is the second most radiologists, breast care nurses and
by the UK Academy of Medical Sciences, fully funding his joint
academic and clinical post in breast surgery.
common cancer after non-melanoma many other allied clinical staff.
Screening for Breast Cancer
Following recommendations by the Forrest report in 1986,
Mr Neill R Patani,1 the National Health Service Breast Screening Program
BSc(Hons) MBBS(Hons) MRCS(Eng.) (NHSBSP) was introduced to the United Kingdom in 1988,
Senior House Officer in Surgery
Michael Douek,1 but full national coverage was only achieved in the mid-
University College London, UK. 1990s [1]. Approximately one-and-a-half million women,
Correspondence and reprint requests: aged 50-70 years, are now screened each year in the United
Mr Michael Douek, Kingdom. National screening programs have been introduced
Senior Lecturer and Honorary Consultant Surgeon,
Department of Surgery, The Medical School Building in many countries, which have formed the International
74 Huntley Street, London, WC1E 6AU Breast Cancer Screening Network (IBSN), a voluntary
Tel: 0207 679 6461, Fax: 0207 679 6462, Email: m.douek@ucl.ac.uk
consortium of 27 countries with active population-based
screening programs. In other countries, mammography may
Key words: Breast, Screening, Mammography, Morbidity, be undertaken outside a national screening program and thus
Mortality, MRI, Review. cannot be reliably audited.
Introduction Screening Modalities
The purpose of screening is to detect breast cancers before they The main screening modality is mammography (Figure 1)
become palpable and, through early treatment, reduce and it has a sensitivity of about 76% for the detection of
mortality. Screening mammography has been demonstrated to breast cancer. ‘Missed’ and interval cancers are well
reduce mortality in women over the age of 50 years, but recognised and may lead to litigation. However, the most
screening from the age of 40 years is still controversial. common source of malpractice claims are those of delayed
diagnosis secondary to interpretive error by the radiologist
[2]. In terms of cost per health-benefit for a population,
mammography is a relatively expensive intervention since it
requires the support of a large multidisciplinary specialist
team. There is a potential harmful effect from the ionising
radiation used in mammography, however the exposure has
been decreasing since its introduction. Estimates of increased
breast cancer risk are relatively small and dependent upon
the mathematical model used.
In view of the drawbacks of mammography, other imaging
modalities have been evaluated for screening. Ultrasound has
been shown to improve the detection of cancers when used
Figure 1: Screening mammograms of a 64 year old lady found to as an adjunct to mammography in women with dense
have bilateral breast cancer (2 large circles) and a further area of breasts. However, increases in sensitivity are associated with
benign microcalcification in the left breast (small circle).
further false positives, reduced specificity and operator
26 Volume 1 Issue 5 • February/March 2007
Edinburgh Trial (1978), Canadian Trial (1980), Stockholm Trial
(1981) and Goteborg Trial (1982).
Despite methodological criticisms of all the screening trials,
meta-analyses from Sweden estimate the reduction in breast
cancer mortality to be 21% [10]. In a recent systematic review
of the seven trials involving approximately half a million
women, a significant reduction in breast cancer mortality was
only observed in a subgroup of trials considered to be sub-
optimal. The authors concluded that screening is likely to
reduce the relative risk of breast cancer mortality by 15-20%,
with an absolute risk reduction of 0.05%. It has been estimated
that for every 2000 women screened for 10 years, one woman
Figure 2: Breast MRI (MIP- maximum intensity projection) of will have her life prolonged [11].
same patient as in figure 1. Both breast cancers are seen. The
right breast cancer is seen to have a rich blood supply.
Breast cancer deaths as a proportion of all female deaths are
higher for women in their forties and approximately one-third
of the life years lost to breast cancer are from this group.
dependence [3]. It has an important role to play in the However, mammographic screening in women below 50 years
investigation of symptomatic women and the evaluation of of age was not found to be beneficial in adequately randomised
screen-detected lesions. The role of ultrasound as a primary trials [11] and is relatively more expensive in view of the lower
screening tool has been assessed in younger women with incidence of breast cancer in this age group. Routine screening
increased breast density, but this is not supported by mammography in this age group is thus controversial and is not
randomised controlled trials [4]. advocated in the UK.
Contrast-enhanced MRI (Figure 2) is a very sensitive test
when compared to mammography but has a lower specificity Potential harm of mammographic screening
and has not been demonstrated to reduce breast cancer Almost one-third of women experience pain at their first
mortality. The greatest clinical utility of breast MRI is in mammogram [12] and this is a major factor in declining further
women at high-risk and those with genetic predisposition. screening invitations [13]. There are also negative psychological
This was demonstrated in several studies including MARIBS, and social consequences of screening. Significant and persistent
a prospective randomised controlled trial [5]. MRI is also distress is associated with screen detected abnormalities,
useful for imaging younger patients with dense breasts [6]. including those which are subsequently confirmed to be benign
However, false-positive findings are well recognised and may [14]. The duration of the period of uncertainty is variable and
require further diagnostic intervention. The National Institute may have an impact on compliance with screening [15]. Recall
for Health and Clinical Excellence (NICE) has recently rates after the first mammogram range from 8-14% and false
published an update on the management of familial breast positives often require invasive tests to exclude carcinoma. In
cancer, recommending the use of breast MRI for screening the US, after ten screening mammograms the cumulative risk of
women with increased susceptibility for breast cancer, a false-positive was found to be almost 50%, with as many as
according to their estimated 10 year risk [7]. one in five women requiring a biopsy [16].
Clinical breast examination has been suggested as an
alternative for developing countries, where the expense of
mammography precludes it as a national screening tool. In 'Mammographic screening reduces
the Health Insurance Plan of New York Trial, which reported breast cancer mortality but does have
a 30% reduction in breast cancer mortality, approximately potential for harm. Women should be
two-thirds of cancers in the screened group were detectable
by clinical breast examination. The Canadian National Breast
adequately informed in order to make
Screening Study 2 (CNBSS2) found no difference in breast their own decision on whether to be
cancer mortality at 13 years when the combination of screened or not.
mammography, clinical breast examination and breast-self
examination was compared with clinical and breast-self
examination alone, [8]. Clinical breast examination alone has As with other screening programmes, the detection of sub-
not been evaluated in randomised trials of breast cancer and clinical pathology may lead to over-diagnosis and the
overall mortality. inflation of incidence figures [17]. Subsequent intervention
Two large population-based studies comparing breast self for benign pathology could be regarded as harmful. Breast
examination as a screening tool with no intervention, have biopsy, lumpectomy, breast-conserving surgery, mastectomy
found no statistically significant difference in breast cancer and the use of radiotherapy have all been found to be greater
mortality [9]. Furthermore, almost twice as many benign in the screened groups compared to controls. In the Canadian
biopsies were performed in the screening group, suggesting the and Malmo Trials, the relative risk of lumpectomy or
potential for increased morbidity. mastectomy was 31% greater in the screened women [11].
This could not be attributed to the greater number of tumours
The evidence for mammographic screening detected by the initial or ‘prevalence’ screen as it was also
Screening mammography has been evaluated in several large observed in the subsequent ‘incidence’ screens.
randomised trials with long follow up. These include the New All breast cancers do not share the same natural history;
York Trial (1963), Malmo Trial (1976, 1978), Two-County Trial the prognosis for women with screen detected cancers is
(Kopparberg 1977, Two-County 1977, Ostergotland 1978), know to be very good [18]. Screening has increased the
Volume 1 Issue 5 • February/March 2007 27
identification of lesions which are clinically undetectable,
radiologically and histologically cancerous but biologically Website recommendations:
benign or ‘non-progressive’ [19]; In particular ductal http://www.cancerscreening.nhs.uk/breastscreen/
carcinoma in-situ (DCIS), which accounted for between one- http://appliedresearch.cancer.gov/ibsn/
quarter and one-third of all screen detected cancers in the http://www.nice.org.uk/guidance/cg41/?c=91496
USA between 1991 and 1998 [20]. The natural history of DCIS http://www.informus.ucl.ac.uk/
is elusive and the five year survival of over 99% suggests that
only a proportion of these progress to invasive carcinoma.
The surgical, radiological and medical treatment of DCIS and
other proliferative breast lesions has the potential to increase References
morbidity and mortality. In England and Wales between 1990 1. Forrest APM. Breast Cancer Screening: Report to the Health Ministers of England,
Wales, Scotland and Northern Ireland. London: HMSO.
and 2001, mastectomy for DCIS in women aged 50-64 years
2. Mavroforou A, Mavrophoros D, Michalodimitrakis E. Screening mammography,
(the screened population) increased by over 400%, whereas public perceptions, and medical liability. European Journal of Radiology
mastectomy for invasive breast carcinoma increased by 20% 2006;57:428-35.
[21]. It is noteworthy that the increased treatment of DCIS has 3. Kolb TM, Lichy J, Newhouse JH. Occult cancer in women with dense breasts:
detection with screening US-diagnostic yield and tumour characteristics. Radiology
not reduced the incidence of early stage invasive breast 1998;207(1):191-9.
cancer, which has in fact continued to increase over the same 4. Irwig L, Houssami N, van Vliet C. New technologies in screening for breast cancer:
period. Similarly in the Netherlands, the introduction of a systematic review of their accuracy. British Journal of Cancer 2004;90:2118-22.
screening in the early 1990’s was associated with an increase 5. Leach MO, Boggis CR, Dixon AK et al. Screening with magnetic resonance
imaging and mammography of a UK population at high familial risk of breast
in the number of women who underwent mastectomy by cancer: a prospective multicentre cohort study (MARIBS). Lancet
2005;365(9473):1769-78.
84% [22].
6. Warner E, Plewes DB, Shumak RS et al. Comparison of breast magnetic resonance
With regard to adjuvant therapy, in the Malmo Trial the imaging, mammography and ultrasound for surveillance of women at high risk for
relative risk of receiving radiotherapy was increased by 24% hereditary breast cancer. Journal of Clinical Oncology 2001; 19(15): 3524-3531.20.
May DS, Lee NC, Richardson LC, Giustozzi AG, Bobo JK. Mammography and
in the screened group [11]. Whilst most of this increase breast cancer detection by race and Hispanic ethnicity: results from a national
represents the treatment of newly diagnosed breast cancer, program (United States). Cancer Causes Control 2000;11(8):697-705.
some represents treatment of proliferative lesions including 7. National Institute for Health and Clinical Excellence (NICE). Familial breast
cancer: the classification and care of women at risk of familial breast cancer in
DCIS. primary, secondary and tertiary care (partial update of CG14) 2006; Reference
CG041.
Conclusion 8. Miller AB, To T, Baines CJ, Wall C. Canadian National Breast Screening Study-2:
13-year results of a randomized trial in women aged 50-59 years. Journal of the
Mammographic screening reduces breast cancer mortality in National Cancer Institute 2000;92:1490-99.
women over 50 years, but between 40-50 years, its use is still 9. Kosters JP, Gotzsche PC. Regular self-examination or clinical examination for
controversial. In the last two decades, breast cancer mortality early detection of breast cancer. In: The Cochrane Database of Systematic
Reviews, 2, 2003. Oxford: Update Software.
has significantly decreased in both screened and unscreened
10. Nystrom L, Andersson I, Bjurstam N et al. Long-term effects of mammography
women. Significant differences remain in national screening screening: updated overview of the Swedish randomised trials. Lancet
policy and consensus over several fundamental issues (e.g: 2002;359(9310):909-19.
screening interval, starting age, screening protocol etc.) have 11. Gotzsche PC, Nielsen M. Screening for breast cancer with mammography.
Cochrane Database of Systematic Reviews 2006. Issue 4. Art. No.: CD001877.
still not been reached. DOI: 10.1002/14651858.CD001877.pub2.
Many women tend to overestimate the benefits of 12. Miller D, Martin I, Herbison P. Interventions for relieving the pain and discomfort
mammographic screening and are not aware of the major of screening mammography. In: The Cochrane Database of Systematic Reviews, 4,
2002. Oxford: Update Software.
harms or controversies which exist [23]. It has been
13. Elwood M, McNoe B, Smith T, Bandaranayake M. Once is enough – why some
estimated that for every 2000 women screened for 10 years, women do not continue to participate in a breast screening programme. The New
Zealand Medical Journal 1998;111:180-3.
200 will experience psychological distress from false
14. Bulow B von. Psykologiske folger af screening for brystkraeft blandt raske kvinder.
positives, 10 women will be treated unnecessarily for a breast
Ugeskrift for Laeger 2000;162:1053-9.
cancer which would otherwise not have been apparent and
15. Brett J, Austoker J. Women who are recalled for further investigation for breast
only one will benefit from a longer life [11]. Mammography screening: psychological consequences 3 years after recall and factors affecting re-
attendance. Journal of Public Health Medicine 2001;23(4):292-300.
increases the absolute number of patients who undergo
16. Elmore JG, Barton MB, Moceri VM, Polk S, Arena PJ, Fletcher SW. Ten-year risk
benign breast biopsy, breast conserving surgery, mastectomy of false positive screening mammograms and clinical breast examinations. The
and radiotherapy. It is thus important that women are advised New England Journal of Medicine 1998;338(16):1089-96.
of the benefits as well as the risks of screening mammography 17. Miller AB. The costs and benefits of breast cancer screening. American Journal of
Preventative Medicine 1993;9:175-80.
so that they can make an informed decision on whether to
18. Moody-Ayers SY, Wells CK, Feinstein AR. “Benign” tumours and “early detection”
take part in national screening programs. in mammography-screened patients of a natural cohort with breast cancer.
For women at high risk, breast MRI can be used for Archives of Internal Medicine 2000;160:1109-15.
screening (alone or in conjunction with mammography) 19. Olsen O, Gotzsche PC. Cochrane review on screening for breast cancer with
mammography. Lancet 2001;358:1340-42.
although there is no evidence that it reduces mortality.
20. May DS, Lee NC, Richardson LC, Giustozzi AG, Bobo JK. Mammography and
Modern screening modalities can lead to an improvement breast cancer detection by race and Hispanic ethnicity: results from a national
in the detection of early abnormalities which may be regarded program (United States). Cancer Causes Control 2000;11(8):697-705.
as precursors of invasive cancer. However, this can cause 21. Douek M, Baum M. Mass breast screening: is there a hidden cost? The British
Journal of Surgery 2003; 90 suppl 1, June: (Abstract Breast 14).
harm by leading to false positives and unnecessary
22. Gotzsche PC. Trends in breast-conserving surgery in the Southeast Netherlands:
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reduce over-diagnosis and interventions which cause 2435-40. European Journal of Cancer 2002;38:1288.
morbidity and do not reduce mortality. 23. Barrat A, Cockburn J, Furnival C, McBride A, Mallon I. Perceived sensitivity of
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Conflicts of interests: none declared. Health 1999; 53: 716-20.
28 Volume 1 Issue 5 • February/March 2007
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