We have shown that throughout 1980–2002, women diagnosed with breast cancer in New South Wales experienced a large, increasing and significant survival advantage over women diagnosed in West Midlands. Similarly, large differences in survival were observed between England and Australia, suggesting that the differences between the 2 regions we examined in detail are also present at a national level.
Differences in survival between West Midlands and New South Wales were most marked amongst older women and amongst women diagnosed with localized disease, but were of a similar magnitude across the socio-economic spectrum. The patterns could not be accounted for by differences in the extent of disease at diagnosis, or by variations in histological type, insofar as the measured variables used in this study represent the true values of these parameters for the women analyzed.
These international survival differences are consistent with the only other comparative study of breast cancer survival between an English and an Australian population.5 Poorer survival amongst older women is also consistent with several detailed analyses of EUROCARE data, which show that in countries with lower overall survival the differences by age are more marked.25–28 Our observation that extent of disease does not help explain differences in survival between Australia and England contrasts with 2 previous international analyses within Europe and between Europe and the USA.29–35 These studies have concluded that a large proportion of the differences in survival between the UK and other developed nations can be attributed to differences in stage at diagnosis.
The patterns observed could result from differences in data quality between Australia and England.
It is possible that the registry in New South Wales selectively under-counts cancer cases with poorer prognosis or fails to register the deaths of more short-term survivors than West Midlands. Either of these biases would artificially inflate survival in New South Wales. We calculated the additional number of deaths needed in New South Wales to equalize 1-year survival by multiplying the excess hazard ratios (Fig. 4) by the number of excess deaths for each age group. This showed that during the period 1980–2002, around 4,500 additional breast cancer deaths would be needed in New South Wales to nullify the differences in 1-year survival, the majority being for women aged 70–99 years. If we assume that these 4,500 deaths occurred solely amongst the cases registered, this would imply that only one-third of the deaths within the first year due to breast cancer amongst registered cases are actually known to the New South Wales Central Cancer Registry and only one-quarter amongst the elderly. We consider this implausible, particularly given the relatively low proportion of death-certificate-only (DCO) cases in New South Wales (an accepted marker of completeness of registration). The alternative interpretation that there were 4,500 women with breast cancer who were never registered, and who also died during the first year after their diagnosis, also seems unlikely. The incidence of breast cancer was indeed higher in West Midlands than in New South Wales during this period, particularly amongst the elderly (Woods et al., submitted). If we assume that the incidence in New South Wales is artefactually low, 2,000 additional cases of breast cancer would have been needed in New South Wales during the period 1980–2002 to equalize the incidence rates. Since this represents less than half of the 4,500 cancer deaths needed to equalize survival for the first year only, under-registration of cancer cases cannot explain the survival differences.
It is also possible that the New South Wales Central Cancer Registry is less successful at matching deaths with cancer registrations because their target population includes a large proportion of recent migrants, who possibly return to their country of birth following a diagnosis of cancer. This phenomenon also seems unlikely to explain the survival differences, however, since the largest differences are observed in the first 12 months after diagnosis when women are receiving first-line treatment for their cancer, a time at which they are unlikely to emigrate. Further, survival differences are greatest amongst the elderly. Emigration from Australia, in contrast, is largely confined to those under 35 years.36
It could be that a higher proportion of the registered tumors are in situ in New South Wales than in West Midlands, but are erroneously registered as localized invasive cancers. To examine this hypothesis, we randomly deleted women with localized cancer in New South Wales, who did not die during the observed follow-up, to establish the proportion of cases that would need to have been in situ to equalize the relative 5-year survival. For all 3 periods of diagnosis, similar 5-year relative survival was reached only after the removal of more than half of these women with localized cancers. It cannot be that so great a proportion of the cancers in New South Wales are in situ, particularly given that the proportion microscopically verified (i.e., confirmed as invasive tumors) during 1980–2002 was more than 80%.
Estimation of survival is sensitive to both the accuracy and the comparability of the rules used to establish the date of diagnosis. This is unlikely to have influenced our results, however, because both New South Wales and West Midlands apply the same rules to determine when a diagnosis took place where more than 1 date is available. Further, the excess hazard of breast cancer death was persistently lower in New South Wales for the entirety of the first 2 years following diagnosis, rather than simply “shifted” to the left (data not shown). If differences in survival were due simply to a difference in the way date of diagnosis had been determined, such a shift in the excess hazard would be expected.
We chose to use a temporally and internationally comparable measure: the unemployment rate to categorize women into socio-economic groups. This is a relatively crude measure of socio-economic status. However, we observed very similar survival patterns for women diagnosed from 1996 to 2002 when using quintiles of 2 highly-validated and locally defined deprivation measures; for West Midlands, the IMD income domain score 2004,37 and for New South Wales, the index of disadvantage of the Socio-Economic Indexes For Areas (SEIFA) 2001.38
In applying a life table derived from deaths in 1990–1992 to the entire period 1980–1995, it was assumed that background mortality from the early 1990s was a good estimate of the true background mortality for each of these 16 years. Although region-specific life tables for 1981, 1991 and 2001 were available for the West Midlands, it was not possible obtain either life tables or deaths data for the years 1980–1982 for New South Wales. It was desirable to use the same approach in each region in order to ensure comparability of the results. Consequently, it was assumed that regional life tables for 1991 provided a good estimate of age-specific mortality in 1980 and more particularly for women older than 50, who represent the majority of breast cancer patients. In fact, the increase in life expectancy of a 50-year old woman was greater in Australia than in England between the periods 1980–1982 and 1990–1992 (1.64 years39 compared with 1.34 years40). This implies that the differences in survival that we present for the earliest years are slight overestimates of the true differences because our estimate of expected survival is likely to be relatively higher for New South Wales in comparison to the West Midlands. The only alternative approach, using national rather than regional life tables, would have biased our results to a greater degree.
Possible causal explanations
Delay in diagnosis
The interpretation that delays in diagnosis are responsible for the international survival differences is not strongly supported by these data because extent of disease at diagnosis does not display much explanatory power. Adjustment for this variable would tend to reduce the estimated excess hazard ratio of death between the 2 countries if the international differences in survival were due to greater delays in diagnosis, longer waiting times for hospital consultation or less effective screening in West Midlands than in New South Wales. Residual confounding by extent of disease may partially account for this. This implies that the accuracy of the extent of disease variable might be lower in West Midlands, so that within each stage grouping, the true (unknown) stage of disease is more advanced in West Midlands than in New South Wales (stage migration).41 This would lead to better extent-adjusted survival in New South Wales since better staging practice tends to lead to more accurate allocation of women into the higher staging categories.
It is also possible that the imputation model used to accommodate missing data on extent of disease was not accurate enough to account for the missing observations. In particular, the proportion of tumors which were unstaged was greatest amongst women aged over 80 years at diagnosis in West Midlands during the years 1988–2002. If these women's disease was more often regional or distant than estimated by the imputation model the impact of extent of disease on the international difference in survival would have been underestimated.
To measure the impact of disease stage upon these differences in survival more accurately, detailed information would need to be re-extracted at source for both populations, using a comparable protocol and similarly trained personnel, as has been done in the EUROCARE high-resolution studies.29 This would enable us to better understand whether the overall differences in survival that we observe here are, in fact, partially due to women in West Midlands being diagnosed later than women in New South Wales.
A second possible explanation for lower survival is different cancer management in West Midlands than in New South Wales. Receipt of treatment by women with breast cancer is influenced by the availability of different treatments, of the decisions made by healthcare professionals, of policies set by the healthcare provider(s) or of differential compliance with treatment by the women themselves.
Survival differences were observed for both localized and regional disease, whereas the survival of women with distant metastases was more similar. Although it is possible that we have overestimated the magnitude of this difference for localized disease, such extent-specific differences still suggest that the overall outcome of treatment with curative intent may be less good in West Midlands than in New South Wales, since women diagnosed with distant disease receive only palliative care. In cancer populations where treatment has been equalized, differences in cause-specific survival between social or racial groups are small or nonexistent.42–46 However, whether patterns of treatment can explain the international survival differences for breast cancer has yet to be examined.
Treatment differences might also be the underlying reason for the age-specific differences and, in turn, the international differences. Differential treatment for breast cancer by age has been observed.47 Prevalent comorbidity is likely to play an important part in accelerating death in the first year after diagnosis because of the contraindication of effective treatment or more severe complications of treatment amongst patients with comorbid conditions. This is one of the explanations that has been given for the fact that older women receive less surgery compared with younger women in West Midlands. Women who have not had surgery are almost always women who have comorbidity (mostly heart conditions) which contraindicate treatment (Personal communication, West Midlands Breast Screening Quality Assurance Reference Centre). This could explain some of the observed international differences in survival, if the management of breast cancer in the presence of comorbidity were substantially different in West Midlands than in New South Wales. It is also possible that treatment may be rationed for elderly patients or that compliance amongst the elderly is particularly low in West Midlands. It is known that during the late 1980s and the early 1990s, there was a tendency to treat elderly women with tamoxifen alone, without surgery.48 If this was occurring to a greater extent in West Midlands, it could partly explain the age-specific differences observed here. However, the largest differences amongst elderly women were observed during the period 1996–2002, suggesting that treatment with tamoxifen only cannot entirely account for these differences. Access to medical services may be more limited for elderly women than younger women, due either to lack of social support or to physical disability, which could also explain a part of this association.
Since no comparative data on treatment were examined in these analyses, in particular on adjuvant endocrine therapy, the treatment modality which has had the greatest impact on breast cancer survival amongst postmenopausal women in the last 30 years,49 it is difficult to draw any firm conclusions regarding the possible role of treatment differentials in these results. Comorbidity has not, so far, been examined in relation to international differences in survival. Although it has been considered as a possible explanation for differences in survival between socio-economic groups,50–52 it has received relatively little attention to date. The investigation of patterns of care in relation to preexisting comorbidity should be a priority for future research.