Breast Cancer Screening for Breast CancerPDF

					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:
intervention. Quality assurance initiatives must seek to               Comment on article by Ernst and collegues European Journal of Cancer 2001; 37:
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
                                                                       mammographic screening: women’s views on test accuracy and financial
                                                                       compensation for missed cancers. Journal of Epidemiology and Community
Conflicts of interests: none declared.                                 Health 1999; 53: 716-20.



28                                                                                                        Volume 1 Issue 5 • February/March 2007

				
DOCUMENT INFO