Breast cancer in elderly compared to younger patients in the Netherlands: stage at diagnosis, treatment and survival in 127,805 unselected patients
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- Bastiaannet, E., Liefers, G.J., de Craen, A.J.M. et al. Breast Cancer Res Treat (2010) 124: 801. doi:10.1007/s10549-010-0898-8
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Breast cancer is the most common type of cancer in several parts of the world and the number of elderly patients is increasing. The aim of this study was to describe stage at diagnosis, treatment, and relative survival of elderly patients compared to younger patients in the Netherlands. Adult female patients with their first primary breast cancer diagnosed between 1995 and 2005 were selected. Stage, treatment, and relative survival were described for young and elderly (≥65 years) patients and within the cohort of elderly patients according to 5-year age groups. Overall, 127,805 patients were included. Elderly breast cancer patients were diagnosed with a higher stage of disease. Moreover, within the elderly differences in stage were observed. Elderly underwent less surgery (99.2–41.2%); elderly received hormonal treatment as monotherapy more frequently (0.8–47.3%); and less adjuvant systemic treatment (79–53%). Elderly breast cancer patients with breast cancer had a decreased relative survival. Although relative survival was lower in the elderly, the percentage of patients who die of their breast cancer less than 50% above age 75. In conclusion, the relative survival for the elderly is lower as compared to their younger counterparts while the percentage of deaths due to other causes increases with age. This could indicate that the patient selection is poor and fit patients could suffer from “under treatment”. In the future, specific geriatric screening tools are necessary to identify fit elderly patients who could receive more “aggressive” treatment while best supportive care should be given to frail elderly patients.
KeywordsBreast cancer Elderly Relative survival Population based
Breast cancer is the most common type of cancer in Western societies and will increasingly become a disease affecting the lives of elderly women. Worldwide, nearly a third of breast cancer occurs in patients ≥65 years, and in more developed countries this proportion increases to over 40% [1, 2]. Despite these numbers, few prospective trials exist have included elderly patients. The population of elderly breast cancer patients is characterized by large individual variation in physical and mental conditions. Combined with the fact that there is limited evidence from Randomized Controlled Trials (RCT), the strong influence of personal preferences in the decision-making process complicates the development of guidelines for the treatment of elderly breast cancer patients [3, 4]. Consequently, up to date there are no generally agreed guidelines for the treatment of elderly females with breast cancer and variation in treatment is large.
Elderly patients are usually diagnosed with more favorable tumor biology: hormone receptor-positive which increase hormone treatment sensitivity, no Her2/neu overexpression, and lower grades and proliferative indices . However, elderly patients are more likely to present with larger and more advanced tumors and are less likely to be treated according to accepted guidelines, which may have a negative effect on survival [1, 6]. Observational studies are suitable to assess achievements in daily medical practice and are useful to study prognosis [7, 8, 9]. Cancer registry data, in addition to RCTs, show actual patterns of staging, treatment and survival by age and therefore offer a possible scope for improvement of care. A recently published review of the population-based literature regarding diagnosis, treatment, and prognosis of breast cancer patients showed that the proportion of patients with unknown stage and advanced disease is higher among elderly patients compared to younger patients and that their treatment is generally less aggressive . Besides, survival of elderly patients is generally lower and the prevalence of (serious) comorbid conditions is usually higher . The possible explanation for the age-related differences regarding treatment is complex; it reflects decisions based on the view of physicians, patients, relatives, and caregivers and on psychosocial issues and costs, but also proximity to an oncology and radiotherapy centre . Because comorbidities and functional status significantly affect prognosis and treatment choices, thorough consideration must be given to the overall health of the elderly patients. However, elderly women are still less likely to have surgery for operable breast cancer, even after accounting for comorbidity, functional status, pretreatment stage, social deprivation, and type of hospital . Comorbidity does not always predict standard treatment; some studies have found an effect of comorbidity, other studies have been contradictory. Studies suggest that treatment decisions for elderly women with breast cancer are still based largely on age rather than health status or potential benefit .
A sizeable proportion of patients older than 70 years with operable breast cancer dies of non-cancer related causes . Consequently, relative survival is the preferred way to describe the prognosis of elderly breast cancer patients, as it takes into account the risk of dying from other causes than the breast cancer. The recent review of Louwman et al.  evaluated all available population-based data concerning elderly with breast cancer and showed several age-related aspects. However, most of the 20 population-based studies that were included in this review were from the SEER database and for the Netherlands only regional data from one regional Cancer Registry were available. Therefore, the aim of this study was to describe stage at diagnosis, treatment, and relative survival of the elderly patients with breast cancer as compared to the younger patients in the Dutch population.
PALGA, the nationwide Dutch network and registry of histo- and cytopathology regularly submits reports of all diagnosed malignancies to the regional cancer registries. The national hospital discharge databank, which receives discharge diagnoses of admitted patients from all Dutch hospitals, completes case ascertainment. Trained registry personnel collect data on diagnosis, staging, and treatment from the medical records, including pathology and surgery reports, using the registration and coding manual of the Dutch Association of Comprehensive Cancer Centers. All data from the regional cancer registries are merged into the Netherlands Cancer Registry (NCR). From the NCR database, adult female patients with their first primary breast cancer diagnosed between 1995 and 2005 were selected. Patients with a history of other malignancy were excluded. The mass mammographic screening program in the Netherlands started between in 1990 and 1991 for females aged 50–70 years; in 1997 the upper age limit of the screening program was increased to 75 years.
Stage was classified according to version of the TNM classification that was used in at the year of diagnosis. Pathological T, N, and M stage was used; clinical stage was used if pathology was missing. Vital status was established either directly from the patient’s medical record or through linkage of cancer registry data with the municipal population registries (until January 1st, 2008) which record information on their inhabitant’s vital status. Relative survival was calculated by the Hakulinen method as the ratio of the survival observed among the cancer patients and the survival that would have been expected based on the corresponding (age, sex, and year) general population. National life tables were used to estimate expected survival. Relative Excess Risks of death (RER) were estimated using a multivariable generalized linear model with a Poisson distribution, based on collapsed relative survival data, using exact survival times. Finally, mortality in the cohort was compared to the overall mortality in the Dutch general population according to age for the total period of follow-up. The estimated percentage of patients that died of breast cancer within the total number of deceased patients was calculated as ((Observed deaths − Expected deaths)/Observed deaths)*100 in the specific age groups.
Characteristics of the Dutch cohort of 127,805 breast cancer patients diagnosed between 1995 and 2005
Year of diagnosis
Stage at diagnosis
Treatment of female breast cancer patients in the Netherlands, according to age
Surgery in all tumors, except T4 and M1*
Radiotherapy after breast conserving surgery*
Mastectomy for In Situ, Stage I or Stage II
Lymph node dissection
Hormonal treatment as monotherapy
Any adjuvant systemic treatment
Relative survival (5-years and 10-years) of breast cancer patients in the Netherlands according to age and stage
In situ (DCIS & LCIS)
Relative survival (95% CI)
Relative survival (95% CI)
Relative survival (95% CI)
Relative survival (95% CI)
Relative survival (95% CI)
P = 0.67
P = 0.004
P < 0.001
P < 0.001
P < 0.001
Our results confirm the international data that indicate a higher stage at diagnosis, less aggressive treatment, less adherence to guidelines, and a decreased survival for the elderly breast cancer patients in the Netherlands. Because of the large number of included subjects, we were able to stratify within the elderly to show that the trends concerning stage and treatment are also present in the patients outside the mass screening program (75+). Although relative survival is lower in the elderly, the percentage of patients who die of their breast cancer is actually low in the elderly.
The field of geriatric oncology has increased in the western countries, although it is still in its early stages . Several population-based studies have shown that elderly patients usually present with more advanced disease, however, few have stratified the elderly into different age groups. Recent data show that the stage distribution of patients aged 70–79 years was almost similar to the stage distribution of the younger age groups for the period of diagnosis 2000–2005, which could be due to the extension of the upper age limit of the screening program to 75 years in 1998 . Women aged 80 years and older, however, remained at higher risk of being diagnosed with more advanced disease in this study. In the present study, we further stratified the age group 70–79 in 2 subgroups and we showed that specifically in the ages 70–74 the stage distribution is similar to the younger patients. After the age of 75, less patients are diagnosed with stage I disease. Moreover, an increasing number of patients were diagnosed with stage III and an unknown stage of disease. This less favorable stage distribution could be due to delay in the diagnosis of breast cancer in elderly patients due to fewer or no screening mammography examinations or patient delay caused by less breast cancer awareness.
Treatment of the elderly population with breast cancer is usually less aggressive than in their younger counterparts. As also shown in the present study, elderly patients receive less surgery as age increases, even in the lower stages of disease, despite the fact that for the elderly population breast cancer surgery-related mortality is low . A recent study of 268 patients above the age of 70 years diagnosed at the Nottingham Breast Institute showed, however, even lower numbers of patients who were operated (60 vs. 80.6% in the present study) . One of the reason for this is that the elderly patients are thought to be at a higher risk of morbidity and mortality; besides personal preferences of the elderly patients also play a role. Hormonal treatment alone without surgery has been considered as alternative treatment option , mainly in the very old. However, as shown in the present data the increase in the use of only hormonal treatment started already at the age of 65. For fit elderly patients it has been confirmed (Cochrane meta-analysis ) that primary hormonal treatment with tamoxifen is inferior to surgery (with or without hormonal treatment) for the local control and progression-free survival of breast cancer, however, no difference in overall survival was shown and data for the frail elderly are not available [1, 14]. Most elderly women with early stage breast cancer are candidates for breast conserving treatment; however, available data suggest that older patients are less likely to receive such treatment . The same trend was observed in the present study: elderly patients with T1 or T2 underwent mastectomy more often when compared to younger patients. Besides, if elderly patients did receive breast conserving surgery (BCS) their chances of receiving radiotherapy were significantly decreased. Several studies have specifically assessed the benefits of radiotherapy in elderly patients and have shown a decrease in the relative rate of breast cancer recurrence [1, 15, 16, 17, 18, 19]. However, the absolute incidence of relapses tended to be low and data on overall survival was generally absent. Finally, elderly patients in the present study received less often a lymph node dissection, also stratified for early and advanced disease. A retrospective study of Aziz et al.  showed a trend toward survival benefit in elderly women with stage I or II breast cancer who underwent axillary lymph node dissection, however, the trend was not significant after adjusting for differences in the probability of receiving a lymph node dissection. Besides, as the authors mention in the discussion, it is difficult to conclude about treatment outcomes in retrospective studies. In conclusion, adherence to guidelines is worse in elderly women; they undergo less surgery and less radiotherapy after breast conserving surgery. A study from Giordano et al.  showed that even after adjustment for comorbidity score, race, marital status, educational status, clinical stage, and tumor characteristics, increased age was independently associated with decreased guideline concordance for surgery, adjuvant chemotherapy, and adjuvant hormonal therapy. A significant part of this deviation from the guidelines could be explained by patient preferences, however, studies are needed to show the extent to which the difference in management can be explained by differences in preferences . It seems, however, that older patients with cancer appear to prefer a more passive role in treatment decisions and that the disparity in treatment by age is not likely to be the sole function of patient preferences [11, 22].
The less aggressive treatment of elderly women in the present study seems to be associated with decreased survival. This could especially decrease the survival of fit elderly patients if the selection for treatment was based only on age. However, effects of treatment on survival are hard to determine by observational research due to confounding by indication. Our study shows a decreased relative survival for elderly patients in all stages of disease. As relative survival reflects disease-specific survival, the results cannot be explained by a higher rate of death in the elderly due to other causes, less intense treatment or either tumor or co-morbid conditions may play a role . A recent trial supported the belief that adjuvant chemotherapy can improve survival among fit elderly women with breast cancer and that standard chemotherapy is superior to the oral agent capecitabine . However, differences between OS and RS are larger for the elderly patients, suggesting that more patients die of other causes; actually as shown in the present study the percentage of patients who die of their breast cancer within the group of deceased patients decreases to around 20% for the oldest elderly, meaning that the largest proportion of patients dies due to other causes. After the age of 75, more than 50% of the deceased patients with breast cancer die of other causes than their breast cancer; so a careful, multidisciplinary evaluation of the elderly patient has to take place.
In conclusion, the present study showed that elderly patients in the Netherlands are diagnosed at a higher stage of disease, receive less aggressive treatment, and have a decreased relative survival. Although relative survival was lower in the elderly, the percentage of patients who died of their breast cancer was actually low in the elderly. This could indicate that patient selection is poor and that fit patients suffer from “under treatment”. Future studies should be aimed at designing specific geriatric screening tools for elderly breast cancer patients which assist in choosing adequate treatment; thereby improving breast cancer specific survival (with minimal toxicity) for fit elderly patients and selecting frail elderly patients for best supportive care.
The authors would like to thank the Dutch Cancer Society (KWF 2007-3968), the Netherlands Cancer Registry (NCR) and Geriatric Oncology in the Netherlands (GeriOnNe).
Conflicts of interest
All authors have no potential conflicts of interest.