Professional Documents
Culture Documents
719
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Surgery
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Figure 2. UK/US, 195099: decrease in breast-cancer mortality at ages
2069 (mean of annual death rates per 100 000 women in component
5-year age-groups).
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Pathological reporting
Provision of appropriate adjuvant therapy depends on
accurate staging of disease. Such staging is influenced not
only by adequate initial surgery, but also by completeness of
subsequent histopathological reporting. In 1993, 45% of
pathologists reporting on breast-cancer specimens had a
special interest in the disease.32 This issue is becoming
increasingly relevant as clinicians become more aware of the
importance of hormone-receptor status (for both oestrogen
and progesterone), as well as special stains such as c-ERBB2.
In a review covering years 198488, Richards and colleagues
found a report of non-specific morphology in 26% of
cases.27 On further analysis, this proportion was 17% for
teaching hospitals, 20% for non-teaching hospitals seeing
more than 50 new cases per year, and 38% for those seeing
fewer than 50 new cases. A similar study looking at care
provided in 1992 found that reporting of tumour grade and
of excision margins improved with caseload of the unit
involved.29 Dey and co-workers similarly found that caseload
was the major determinant of completeness of reporting,
noting no significant difference between teaching and nonteaching hospitals of equivalent size.33 The 1987/1993
Scottish audit found pathological reports in 87% of 1987
case-notes and 90% of those from 1993, with wide variation
between Health Boards (66100%).24 Information on
tumour size and grade improved over the study period,
THE LANCET Oncology Vol 2 December 2001
Radiotherapy
Recent work has suggested that postoperative radiotherapy
of the breast can affect survival as well as local recurrence.37
It should be offered to virtually all patients who undergo
breast-conserving surgery for invasive disease, as well as a
proportion of those undergoing mastectomy. In a 1993
postal survey of UK oncologists, only 70% reported an
agreed local policy for provision of radiotherapy.32 Two UK
audits of treatment provided in the 1990s reported that the
overall proportions for patients undergoing breastconserving surgery who were not subsequently referred for
radiotherapy were 10% and 25%, respectively.38,39 Significant
association between caseload and likelihood of referral for
radiotherapy was observed: 32% referral from surgeons with
the lowest caseload compared with 86% from those having
the highest caseload (p < 0.0001 for trend).38 Basnett and
colleagues found that referral for radiotherapy was more
likely in teaching than in non-teaching hospitals,28 and the
Yorkshire group noted wide variation in referral between
different districts within the county, unrelated to variations
in use of breast-conserving surgery.23 The Scottish Audit
noted an increase in rates of referral for radiotherapy after
breast-conserving surgery from 55% in 1987 to 75% in 1993,
but they found no variation by surgical caseload.24 The
actuarial rate of local recurrence for the 1987 patients was
6% for those who had received radiotherapy and 25% for
those who had not, with overall rates ranging from zero to
20% when analysed by Health Board of initial referral.
Studies in the USA have found age and stage of disease, in
addition to type of institution, lack of local facilities, and
urban location, to be significant determinants of provision
of radiotherapy after breast-conserving surgery,12,16,40 as well
as noting broader regional variations.41
721
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Adjuvant systemic therapy
Adjuvant systemic therapy can be in the form of endocrine
manipulation or chemotherapy. Previous surveys have
revealed wide variation in provision of systemic treatment,20
with apparently greater use in teaching than in non-teaching
hospitals.28 Sainsbury and colleagues review of management
of breast cancer throughout Yorkshire showed that patients
under the care of a surgeon with a special interest in breast
cancer were more likely to receive both endocrine-based
therapy and chemotherapy.23 Along with consultant
caseload, use of chemotherapy was the characteristic most
closely associated with survival.42 These findings may well
relate to the increased likelihood of involvement of an
oncologist by specialist breast surgeons, because referral to
an oncologist influences the ultimate provision of adjuvant
therapy.43 Unfortunately, the UK has fewer cancer specialists
per head of population than any other European country.44
The advent of the multidisciplinary team, with regular
discussions between surgeons, oncologists, radiologists, and
pathologists, should reduce the variability of provision of
adjuvant systemic therapy. However, in a postal survey of
UK oncologists in 1993, only 20% of those who replied were
involved in multidisciplinary discussion before surgery;32 the
proportion is likely to have changed since that time.
Furthermore, only 56% reported an agreed policy for
provision of adjuvant systemic therapy, with great variation
noted between different policies.
For patients receiving inadequate adjuvant therapy, the
inadequacy seems to apply over a range of modalities. A
199596 audit in the South Thames region showed that
patients who received radiotherapy after breast-conserving
surgery had a greater chance of being prescribed tamoxifen
than those who did not (95% versus 25%).38 In 1987,
Twelves and co-workers reviewed breast-cancer
management for the whole of Scotland in a single year to
limit the effect of changes in practice over time.45 They found
that the treating health board was an independent predictor
of use of adjuvant systemic therapy, supporting the notion
that the problem is as much one of service organisation as of
differences between individuals.46
Survival
Gillis and Holes review of breast-cancer management in the
west of Scotland for the years 198088 compared survival for
patients treated by specialist and non-specialist surgeons.30 At
5 years, overall survival was 67% and 58%, respectively, and
that at 10 years 49% compared with 41%. The study period
predates the introduction of mammographic screening, and
differences were observed across all patients and disease
subgroups; the largest difference was 19%. The relative
hazard ratio for women under the care of a specialist surgeon
compared with those treated by a non-specialist was 0.83
(95% CI 0.740.92) after adjustment for age, deprivation
index, and tumour size. If nodal involvement was also taken
into account, the hazard ratio was 0.84 (0.750.94) . The
actual treatment received was not included as part of the
analysis, though the noted differences seem to exceed any
discrepancy that could be attributed to use of adjuvant
systemic therapy.47 In the review by Twelves and colleagues of
patterns of breast-cancer care throughout Scotland in 1987,
722
Clinical trials
With continuing rapid advances in management of breast
cancer, there may be a problem in keeping up to date with
THE LANCET Oncology Vol 2 December 2001
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Review
Other factors
Studies from migrant populations have suggested that
differences in incidence of breast cancer among countries
are social and environmental, rather than genetic, in origin;
only about 5% of cases of breast cancer are due to highly
penetrant dominant genes.3 Though no convincing link has
ever been shown between incidence and survival, the
obvious association between breast cancer and external
influence supports the hypothesis that social and
environmental factors influence the biological behaviour of
the disease. A UK study of 5-year survival after treatment for
breast cancer showed rates of 70% and 57% for the most
affluent and least affluent tenths of the community studied.59
A small study from the Netherlands (271 patients in
total) compared the histopathological features of breast
cancers in laboratories serving two regions, in which 10-year
survival for breast cancer was 48% and 69%, respectively,
despite similar surgery and radiotherapy protocols (the
study predated the advent of mammographic screening and
of adjuvant systemic therapy).60 Age distribution of patients,
tumour size, and lymph-node status did not differ
significantly between the two cohorts, and nor did
histological and nuclear grade (according to World Health
Organisation criteria). However, the mitotic activity index
(the number of mitotic figures in a set number of
neighbouring fields) and mean nuclear area (area measured
at 2000 magnification) both showed significant differences
between the regions (p < 0.0001). At the time of another
study of the specimens from one of the regions 15 years
later, the features particular to that area were still present.
These differences could not be attributed to specific factors,
although one region was far more industrialised than the
other. In the USA, breast-cancer mortality has long been
known to be higher for women living in the northeastern
THE LANCET Oncology Vol 2 December 2001
Discussion
There has clearly been great variation in management of
breast cancer within the UK, with poor adherence to
consensus guidelines, although the situation is improving.
Although data are sometimes confounding and
contradictory, such variation seems to affect survival
significantly. True comparisons between sets of data are
possible only if data-collection techniques and accuracy are
themselves comparable, which may call into question at least
the magnitude of some of the differences observed between
countries. A study of factors affecting breast-cancer survival
is inevitably retrospective in nature, such that better
understanding from future investigations depends on
application of the most rigorous standards to data
collection. However, studies cited here, in which methods of
data gathering have been uniform have shown significant
survival differences between individual clinicians,
institutions, and health-service organisations.
There is an increasing body of evidence in support of the
trend towards greater subspecialisation; patients fare best
when referred to a surgeon with a special interest in breast
cancer, seeing large numbers of new cases, and working as
part of an integrated multidisciplinary team. The large
differences in deaths within 6 months of diagnosis between
the UK and other European countries cannot be explained
by treatment differences alone, and are likely to reflect either
delayed presentation or biologically more virulent disease.
There is indirect evidence of the influence of socioeconomic
factors on survival, but the suggestion that provision of care
to women with breast cancer within the UK has been nonuniform and at times inadequate remains difficult to refute.
At the very least, we should aim to standardise care so as to
obtain maximum survival benefit, and strategies for
achieving this aim in the future are now being introduced.
In England, the Department of Health has overseen the
establishment of Regional Cancer Networks. Tumour-sitespecific groups, consisting of members of the
multidisciplinary teams from across the region, will
determine a pathway of care based on national guidelines
across the network. A similar system has been set up in
Scotland with the recently established Clinical Standards
Board, which will ensure that nationwide management is in
line with basic treatment protocols.
723
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Acknowledgments
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725
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