SE performed all of the analyses, contributed to the interpretation of the data, and drafted the article. PWD contributed with the analysis and interpretation of the data. LB contributed with the acquisition of the data, with detailed knowledge about the register, and with revising the article for intellectual content. LH contributed with the conception and the design of the study, interpretation of the data, and revising the article for intellectual content.
The authors have declared that no competing interests exist.
Several reports have shown that less aggressive patterns of diagnostic activity and care are provided to elderly breast carcinoma patients. We sought to investigate whether differences in the management of older women with breast cancer are associated with survival.
In an observational study using a population-based clinical breast cancer register of one health-care region in Sweden, we identified 9,059 women aged 50–84 y diagnosed with primary breast cancer between 1992 and 2002. The 5-y relative survival ratio was estimated for patients classified by age group, diagnostic activity, tumor characteristics, and treatment. The 5-y relative survival for breast cancer patients was lower (up to 13%) in women 70–84 y of age compared to women aged 50–69 y, and the difference was most pronounced in stage IIB–III and in the unstaged. Significant differences in disease management were found, as older women had larger tumors, had fewer nodes examined, and did not receive treatment by radiotherapy or by chemotherapy as often as the younger women. Adjustment for diagnostic activity, tumor characteristics, and treatment diminished the relative excess mortality in stages III and in the unstaged, whereas the excess mortality was only marginally affected in stage IIB.
Less diagnostic activity, less aggressive treatment, and later diagnosis in older women are associated with poorer survival. The large differences in treatment of older women are difficult to explain by co-morbidity alone.
A study from Sweden shows that a lower 5-year relative survival for older women with breast cancer was associated with less diagnostic activity, less aggressive treatment, and later diagnosis.
Breast cancer is the most common cancer in women in much of the developed world; for example, there are 41,000 new cases in the UK per year. In 2003, 6,869 women were diagnosed with breast cancer in Sweden. Survival has improved greatly; in the past ten years in the UK, the risk of dying of the disease has fallen by one-fifth. The disease is rare in women under 30 years, but the risk of breast cancer increases with age. Although there are a number of treatments for breast cancer, previous work has suggested that certain factors may affect whether a woman gets treatment. For example, older women are less likely than younger women to be entered into trials of treatment for breast cancer, and therefore treatment guidelines are not as clear for older women. They may also be less likely to receive breast cancer screening.
The researchers wanted to look at whether the age of women affected both their survival rate and the treatment they were likely to receive for breast cancer.
They studied 9,059 women aged 50–84 years, diagnosed with primary breast cancer between 1992 and 2002 in one health-care region in Sweden. The researchers found that relative survival over five years of women between 70 and 84 years of age was up to 13% lower compared to women aged 50–69 years. The difference in survival was most pronounced in women who had been shown to have more advanced disease or in whom no assessment of the stage of the disease had been made. There were significant differences in disease management found; older women had larger tumors, had fewer lymph nodes examined, and did not receive treatment by radiotherapy or chemotherapy as often as the younger women.
In older women, the diagnosis of breast cancer was often made later than in younger women. Once diagnosed, older women were less likely to be fully investigated for their cancer, and had less aggressive treatment. It is possible that other illnesses (co-morbidities) in these women may have meant that they were less likely to survive the cancer, but this cannot be the main cause of the differences, and diagnosis in older women is associated with poorer survival. The large differences in treatment of older women are difficult to explain by co-morbidity alone. Even in a country such as Sweden with good health care, age results in great differences in the diagnosis and care of women with breast cancer, with older women faring much worse than younger women.
The US National Cancer Registry has a page with many links to information on breast cancer, including prevention and treatment:
Cancer Research UK, a large UK charity that funds research into breast cancer, has many pages of patient information:
Swedish Cancer Registry:
Regional Oncologic Centre in Uppsala/Örebro Region:
Swedish Cancer Society:
Age should not be a determinant for quality of care in breast cancer. In Sweden, as in many other countries, the population is ageing with a rapidly increasing number of elderly women diagnosed with breast cancer as a consequence. Today about 30% of all breast cancer patients in Sweden are 70 y or older at diagnosis [
The aim of our study was to investigate whether the differences in management and diagnosis of breast cancer in older women have an effect on the survival. We based our analysis on a population-based clinical database including information on diagnostic activity, tumor characteristics, and treatment.
We used a population-based regional breast cancer register for the Uppsala/Örebro health-care region. The register was established in 1992, at the same time as formal written clinical guidelines were issued for the region with the aim to ensure that all women with breast cancer had the same opportunity to receive high-quality care. The region comprises seven counties in Sweden with a total population of about 1.9 million. The register includes individual information about vital status, age, and date of diagnosis, detection mode, tumor-stage, biological tumor characteristics, and primary surgical and oncological treatment. The register includes 97% of all breast cancer patients diagnosed within the region as validated against the mandatory reporting to the Swedish Cancer Registry. The main treatment variables and the staging information have been validated in the register and over 95% agreement was found.
Within the Uppsala/Örebro health-care region, all women aged 50–69 y are regularly invited to mammography screening for a low out-of pocket fee. Additional age groups are also invited to screening in some counties, i.e., the age group 40–49 y in five counties, the age group 45–49 y in one county, the age 70 y in one county, and the age group 70–74 y in three counties.
Participants were all women with primary breast cancer reported to the Uppsala/Örebro regional breast cancer register from January 1992 to December 2002 (12,163 women), with follow-up until December 2003. We excluded 2,169 (17.8%) women who were under 50 y of age and 867 (7.1%) who were older than 84 y. We chose women 50–69 y as a reference group for the elderly, since women 50–69 y were uniformly offered mammography screening and had well-defined treatment recommendations [
The data used in the study are based on quality assurance registers legally required for quality assurance of Swedish health care. The registers are inspected by the Swedish Data Inspection Board.
We compared the 5-y relative survival for primary breast cancer patients in different age groups (50–69, 70–74, 75–79, and 80–84 y). The relative survival ratio (RSR) is the ratio of the observed survival in the population of interest to the survival that would have been expected had the patients experienced only the age- and period-specific mortality of the general population from which they were drawn [
We thereafter stratified the women according to breast cancer stage to study whether the differences in survival between ages were consistent across levels of this variable.
To investigate possible differences in management and treatment of younger versus older patients, we used the Fisher's exact test, which tests the independence between age (dichotomized into 50–69 y versus 70–84 y) and the diagnostic and treatment variables. The
We also constructed a low treatment activity index for women diagnosed with stage I–III breast cancer and for whom stage was not definable. The low treatment activity index was constructed from the evidence-based clinical practice guidelines for breast cancer [
Lastly, we studied differences in survival between the ages while adjusting for the potential determinants (categorized as explained above) by modeling the excess mortality (RER) using Poisson regression [
We used the analysis of variance to explore the variation of tumor size in different age groups (
There were large differences regarding how the breast cancer was detected, i.e., the older the woman, the lower the probability that her cancer was detected by mammography screening (
The unadjusted 5-y relative survival for breast cancer was significantly lower (by up to 13 percentage units) among women aged 75–79, and 80–84 y compared to that for women aged 50–69 y (
Diagnostic activity and treatment differences were observed between women aged 50–69 y and 70–84 y in all stages.
Whereas no major proportional difference in proliferation status and estrogen receptor status were found between the ages in stages I–IIB, a
For the stages III–IV and the unstaged (
We found three statistically significant interactions (of 12 examined) between age and type of treatment and excess mortality, all within stage III. The RER, comparing women not receiving any surgery to those receiving surgery, was four times higher among the younger compared to the older (RER 6.4 versus 1.5, respectively), whereas the RERs comparing excess mortality among women who received radiation versus no radiation, and chemotherapy versus no chemotherapy were both lower among younger compared to the older women (RER 0.3 and 0.4 for younger women compared to 0.9 and 1.3, respectively, among the older) (data not shown).
We found large and clinically relevant absolute survival differences disfavoring women aged 70–84 y as compared to women aged 50–69 y. Due to the Swedish mammography screening policies, the stage distribution was more unfavorable among the older, but an adjustment for stage could only partly explain the survival differences. Looking at relative survival stage by stage, the prognosis was worse in stage IIB and higher among women over 70 y as compared to those 50–69 y. Consistently over the stages we found less diagnostic activity, less use of breast conservation, considerably less use of chemotherapy, higher “low activity index,” and more often treatment in local hospitals in older women. Adjusting for these factors in models largely explained the differences by age group, except for women in stage IIB. Our large population-based register lends further strong support to previous reports [
We used a population-based database with high coverage and little misclassification of the variables used in this analysis. Another strength is that relative survival provides a measure of the excess mortality experienced by breast cancer patients, irrespective of whether excess mortality is directly or indirectly attributable to cancer [
An important explanation for the poorer survival among the elderly was the unfavorable stage distribution due to considerably less mammography screening activity after 70 y and no screening taking place after 74 y. This explanation points to an important health policy issue as the population ages. In many Western countries today, a 70-y-old woman has a life expectancy of 12–16 y.
In stages IIB and higher, radiotherapy was less often used in older women, and this could not be explained only by the less frequent use of breast conservation in the elderly. Radiotherapy in itself, although very effective in reducing relapses also among elderly [
Only a very small proportion of the older women received chemotherapy. This is a consequence of the fact that the guidelines during this time period often have suggested upper age limits of 65–70 y for recommending chemotherapy. The evidence base for effectiveness of chemotherapy in the elderly is considered weaker than for younger women and only a few studies of the effect of chemotherapy have included women over 70 y [
Tamoxifen was widely used in older women in our study. One possible reason for the difference in use (to the disadvantage of the younger patients) is that during the first half of the 1990s, tamoxifen was considered to have a negligible effect in younger patients and was therefore not given to those who received chemotherapy. However, we also found that with higher age, an increasing proportion of women with receptor-negative tumors were treated inappropriately with tamoxifen. A possible interpretation of this finding is that clinicians felt that some treatment activity is warranted in women perceived to have a moderate or high risk of recurrence, but that, in the absence of guidelines regarding chemotherapy, the clinician took the chance that tamoxifen would provide some benefit but little harm.
In summary, elderly women were disfavored in several ways: less use of mammography screening, lower diagnostic activity, and lower treatment activity, leading to a lower relative survival. This is a very distressing finding, since around 30% of all breast cancer patients are above the age of 70 y. There is an acute need for more empirical evidence about the effectiveness and tolerability of different treatments in elderly women. Likewise, it is probable that better structured guidelines for elderly women would be a means to improve the situation.
We want to express our sincere gratitude to all past and present members of the Uppsala/Örebro Breast Cancer Study Group who collected the data and maintained its quality. The work was performed at the Regional Oncologic Centre (ROC), University Hospital, SE-751 85 Uppsala, Sweden. The study was supported by grants from the Swedish Cancer Society. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
breast-conserving surgery
confidence interval
estrogen receptor–negative breast cancer
estrogen receptor–positive breast cancer
negative lymph node involvement
positive lymph node involvement
relative excess rate
relative survival ratio.