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Originally published as JCO Early Release 10.1200/JCO.2003.02.046 on August 11 2003 © 2003 American Society for Clinical Oncology Undertreatment Strongly Decreases Prognosis of Breast Cancer in Elderly Women
From the Geneva Cancer Registry, Institute for Social and Preventive Medicine, Geneva University; Clinic of Gynecology, Senology, Department of Obstetrics and Gynecology; Division of Radiation Oncology; Department of Radiology; and Division of Oncology, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland. Address reprint requests to Christine Bouchardy, MD, Geneva Cancer Registry, 55 Boulevard de la Cluse 55, 1205 Geneva, Switzerland; e-mail: christine.bouchardymagnin{at}imsp.unige.ch.
Purpose: No consensus exists on therapy of elderly cancer patients. Treatments are influenced by unclear standards and are usually less aggressive. This study aims to evaluate determinants and effect of treatment choice on breast cancer prognosis among elderly patients.
Patients and Methods: We reviewed clinical files of 407 breast cancer patients aged Results: Age was independently linked to the type of treatment. Overall, 12% of women (n = 48) had no treatment, 32% (n = 132) received tamoxifen only, 7% (n = 28) had breast-conserving surgery only, 33% (n = 133) had mastectomy, 14% (n = 57) had breast-conserving surgery plus adjuvant therapy, and 2% (n = 9) received miscellaneous treatments. Five-year specific breast cancer survival was 46%, 51%, 82%, and 90% for women with no treatment, tamoxifen alone, mastectomy, and breast-conserving surgery plus adjuvant treatment, respectively. Compared with the nontreated group, the adjusted hazard ratio of breast cancer mortality was 0.4 (95% CI, 0.2 to 0.7) for tamoxifen alone, 0.4 (95% CI, 0.1 to 1.4) for breast-conserving surgery alone, 0.2 (95% CI, 0.1 to 0.7) for mastectomy, and 0.1 (95% CI, 0.03 to 0.4) for breast-conserving surgery plus adjuvant treatment. Conclusion: Half of elderly patients with breast cancer are undertreated, with strongly decreased specific survival as a consequence. Treatments need to be adapted to the patient’s health status, but also should offer the best chance of cure.
BREAST CANCER is the most frequently diagnosed cancer among women in industrialized countries and accounts for at least one third of all cancer cases.1 It is primarily a disease of older women and the risk increases with age. In aging populations, breast cancer among the elderly is a major public health concern.
In Switzerland, the Canton of Geneva presents the highest incidence rates of breast cancer in Europe.1 The life expectancy is particularly high among Swiss women (82.5 years); women aged Despite the increasing number of elderly cancer patients, treatment recommendations for this group are often inconsistent and quite different from those for younger women.4,5 Elderly patients are usually excluded from clinical trials,6 and treatment approaches are therefore influenced by unclear considerations such as the uncertainty about the natural history of disease or even the physician’s preference.7,8 Several studies have documented important differences in the management of breast cancer among these patients.7–13 In general, elderly patients tend to receive less aggressive therapy.7–11,14 However, to date the consequences of therapeutic disparities, and more particularly of undertreatment of the elderly, have been poorly assessed.9–11 Outside clinical trials, cancer registries provide the unique opportunity to evaluate treatments given in routine practice and to assess the influence of treatments on prognosis. These population-based data can help clinicians to evaluate and improve the quality of breast cancer care in elderly patients.
This study evaluates the determinants and the effect of treatment on prognosis among women aged
The data were derived from the Geneva cancer registry, which records all incident cancers occurring in the population of the canton (approximately 420,000 inhabitants). The registry collects information from various sources, and is considered accurate, as attested by its low percentage (< 2%) of patient cases recorded from death certificates only.15 Every hospital, pathology laboratory, and practitioner is requested to report all cancer cases. Trained registrars systematically abstract data from medical and laboratory records. Physicians regularly receive questionnaires to secure missing clinical and therapeutic data. Death certificates are consulted systematically. Recorded data include sociodemographic information, manner of discovery, type of confirmation, tumor characteristics (coded according to the International Classification of Diseases for Oncology16), hormonal receptor status, stage of disease at diagnosis, treatment during the first 6 months after diagnosis, survival status, and cause of death. The registry regularly assesses survival. In brief, the index date refers to the date of confirmation of diagnosis or the date of hospitalization if it preceded the diagnosis and was related to the disease. In addition to passive follow-up (routine examination of death certificates and hospital records), an active follow-up is performed routinely each year using the files of the Cantonal Population Office, which is in charge of the registration of the resident population. Cause of death is established from clinical records and coded according to the WHO classification.17
The study included all breast cancer cases occurring among women aged
Staging was based on the tumor-node-metastasis system classification.18 We considered the pathologic tumor-node-metastasis system or, when absent, the clinical tumor-node-metastasis system classification. Tumor was classified as Tis (in situ), T0 (nonpalpable), T1 (
Breast cancer morphologic subtypes considered were ductal carcinoma, carcinoma not otherwise specified, other, and unknown (no microscopic confirmation).16 The steroid receptors were classified as positive ( Additional data on general health status and comorbid disease at the time of hospitalization were abstracted from clinical files as described by Coebergh et al.19 General health status was recorded as good, moderate, bad, and unknown. Comorbid diseases were classified as follows: cardiovascular, cerebrovascular, other neurologic (including dementia), respiratory, endocrine, renal, gastrointestinal, connective tissue (including rheumatoid arthritis), other cancers occurring more than 5 years before breast cancer diagnosis, and other (including hypertension). Severity of comorbid conditions were classified as (1) acute exacerbation or subacute condition representing a current medical management problem, (2) chronic condition not representing a current medical management problem or currently well managed, or (3) unknown. When several comorbid conditions were present, we considered only the three most important conditions. Information was also collected on complete or partial refusal of the proposed treatment by the patient or a family member.
Statistical Analysis: Determinants of Treatments
Statistical Analysis: Estimation of the Effect of Treatment
Since its creation in 1970, the registry has recorded data for more than 7,800 women with breast cancer. This study analyzed all of the 407 breast cancer patient cases occurring among women aged  80 years between 1989 and 1999. Patient characteristics and their effect on mortality are described in Table 1 . The median age at diagnosis was 84 years (range, 80 to 101 years).
Information on general health status and comorbid condition was not available for 26% and 20% of the women, respectively. Forty percent presented in good health status and 42% had no or had well-managed chronic comorbid conditions. The most frequent comorbid diseases were cardiovascular (43%), hypertension (25%), connective tissue (17%), endocrine (12%), gastrointestinal (8%), respiratory (10%), neurologic (6%), dementia (13%), depression (4%), and cachexia (5%).
Table 2
Treatment modalities and their corresponding effect on mortality are presented in Table 3 . Fourteen percent of patients or their families (n = 56) refused all or part of proposed treatment options. Twelve percent (n = 48) did not receive any treatment, 32% (n = 132) received tamoxifen only, 7% (n = 28) had breast-conserving surgery without adjuvant radiotherapy (n = 28), 14% had mastectomy (n = 55), 14% (n = 57) had breast-conserving surgery plus adjuvant therapy (30 patients had radiotherapy with or without other adjuvant treatment, 26 patients received tamoxifen, one patient received chemotherapy), 19% (n = 78) had mastectomy plus adjuvant therapy (56 patients received tamoxifen, 23 patients received radiotherapy with or without other adjuvant treatment, two patients received chemotherapy), and 2% (n = 9) had miscellaneous treatments (adjuvant treatment alone or in combination). Among women who had surgery, 6.5% (n = 14) had positive surgical margins and axillary lymph node dissection was performed in 62% (n = 136). The mean number of removed lymph nodes was 14 (range, 1 to 39). No patients had sentinel node biopsy. Only 10 women (2%) received chemotherapy.
Factors influencing treatments are listed in Table 4 . The oldest women (> 85 years), women with poor general health status, or women presenting with acute or subacute comorbid conditions were less likely to undergo surgery. However, poor general health status was present in only 17% of the women who did not have surgery. Breast-conserving surgery was more frequent in the private healthcare sector. Tamoxifen was given regardless of the results of the estrogen receptor status testing: the proportion of women receiving tamoxifen was 61%, 60%, and 61% for positive, negative, and unknown estrogen receptor status, respectively.
Among the 407 women, 235 deaths were recorded; 98 were the result of breast cancer, and 137 were the result of other causes. Two women were lost to follow-up. Five-year overall and specific survival was 34% (95% CI, 29% to 39%) and 65% (95% CI, 59% to 71%), respectively.
Tables 1
Table 3
Figure 1
This study shows that elderly women with breast cancer have late diagnosis, incomplete diagnostic assessment, and lack a standardized therapeutic approach. Nearly 50% of the patients had suboptimal treatments, resulting in a large excess of preventable breast cancer mortality. This study is not randomized. Even when adjusting the Cox model on all available variables linked to treatment choice or prognosis, we cannot avoid selection bias related to unrecorded factors. Therefore, the differences found in the risk of mortality can reflect lower propensity to give ad hoc treatment to elderly patients with putative poorer prognosis. However, it is not ethically possible to plan randomized trials that compare therapeutic abstention, unconventional treatments, and standard treatments. Observational studies are the only sources of evidence on the effect of therapeutic options in elderly patients. Delayed diagnosis and incomplete work-up are well-documented phenomena among elderly patients.9,11,22 We found that only one fourth of patients had stage I disease. Approximately one third of the patients had no microscopic or only cytologic confirmation, which results in low determination of exact histology, grade, and estrogen receptor status. It is even more difficult to adopt an appropriate strategy without sufficient information on pathologic tumor characteristics. Several previous studies have shown great disparities in breast cancer treatment and outcome among elderly patients. However, treatment and data on outcome were derived from surgical series and, contrary to this study, did not evaluate the consequences of therapeutic abstention.9,10,14,23 In this study, only 47% of elderly women received standard treatment compared with 91% of women aged 50 to 79 years (n = 2,107) recorded in the registry for the same period (data not shown). Clinical abstention was not always due to medical reasons, and age per se was a strong determinant of treatment choice. Undertreatment strongly decreases patients’ prognoses. In addition to individual damage, public health consequences are also important because numerous elderly women are affected, and the costs of palliative treatment needed when metastases occur are high. We observed that elderly patients without treatment had low specific 5-year survival (46%). Unconventional treatments such as radiotherapy alone had a similar effect as therapeutic abstention. Five-year specific survival also was low among women who received tamoxifen alone (51%) when compared with women who had breast-conserving surgery plus adjuvant treatment (90%).
Breast cancer management in elderly women remains a complex problem for clinicians; there is disagreement about the optimum treatment. Part of this controversy results from some common misconceptions, such as the elderly have less aggressive forms of the disease, they have a limited life expectancy because of comorbid conditions, or that breast cancer mortality among the elderly is a relatively marginal problem because of the increased risk of death from other causes. We found that women In the future, more attention needs to be given to elderly women to diagnose breast cancer at an earlier stage. Elderly women must benefit from noninvasive breast biopsy techniques permitting better diagnostic assessment with minimum inconvenience. Treatment needs to be adapted to the patient’s general health status and comorbid conditions, but has to offer the best chance of cure, regardless of age. Women must be informed about available treatment options and the consequences of undertreatment. In particular, tamoxifen alone should be considered as an alternative only for nonoperable women.
The authors indicated no potential conflicts of interest.
We thank S. Blagojevic for her editorial assistance, and H.M. Verkooijen and B. Aylward for their useful comments on the manuscript. We also thank the registrars of the Geneva Cancer Registry for collecting additional data on comorbidity and general health status.
Presented as a poster at the 25th San Antonio Breast Cancer Symposium, December 11–14, 2002.
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Copyright © 2003 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
2 cm), T2 (>2 to 5 cm), T3 (> 5 cm), T4 (invasion to chest wall or skin and inflammatory carcinoma), and Tx (unknown). Lymph node invasion was classified as N0 (no invasion), N1 (movable axillary), N2 (fixed axillary), and Nx (unknown). Metastasis was classified as M0 (absent), M1 (present), or unknown (Mx). Stages were classified into five groups: stage I (T1 and N0), stage II (T0 or T1, and N1; T2, and N0 or N1; and T3 and N0), stage III (T0 or T1 or T2, and N2; T3, and N1 or N2; T4 and any N; and any T and N3), stage IV (M1), and unknown. 
