Age and Adjuvant Breast Cancer Treatment: Equal Dose, Equal Response
Age and Adjuvant Breast Cancer Treatment: Equal Dose, Equal Response
Abstract & Commentary
William B. Ershler, MD,
INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced
Studies in Aging, Washington, DC, is Editor for Clinical Oncology Alert.
Synopsis: Post-surgical treatment of node-positive breast cancer with chemotherapy has been shown to reduce tumor recurrence and mortality, but the value of such therapy in geriatric populations has not been firmly established. In the current analysis of 4 large Cancer and Leukemia Group B trials spanning 25 years, there was no association between age and disease-free survival or cancer mortality. However, overall survival was significantly worse for older women, presumably from causes other than breast cancer.
Source: Muss HB, et al. JAMA. 2005;293:1073-1081.
Adjuvant chemotherapy for early breast cancer has reduced the risk for disease recurrence and breast cancer mortality for both pre- and postmenopausal women. However, the data are less clear for older patients and fewer receive, or are even offered, systemic chemotherapy even if all indicators suggest a high risk of relapse. Muss and colleagues from the Cancer and Leukemia Group B (CALGB) performed a retrospective review of data from 4 randomized trials that accrued patients from academic and community medical centers over a quarter of a century (1975 through 1999). All trials randomized patients to different regimens, doses, schedules and durations of chemotherapy and all had a treatment arm with doses or schedules that were regarded to be high and potentially more toxic. Of the 6487 enrolled patients, 8% were 65 years or older and 2% were 70 years and older.
By multivariate analysis, smaller tumor size, fewer positive nodes, more chemotherapy, and tamoxifen use were all significantly (P < .001) related to longer disease-free and overall survival. Patient age, however, was not associated with disease-free survival. Older women and younger women derived similar reductions in breast cancer mortality and recurrence. Nonetheless, those patients 65 years and older had worse overall survival compared with younger patients, no doubt due to competing causes of mortality. Furthermore, there was an increase in treatment-related mortality in older patients.
Thus, older women deemed eligible for enrollment on clinical trial were shown to benefit to the same degree as younger counterparts, although there is an increased risk of treatment-related mortality.
Comment by William B. Ershler, MD
This important contribution highlights what most oncologists are coming to appreciate—cancer in older patients may be treated effectively by drugs and schedules derived and previously tested in younger patients. But, despite the newsworthiness of the report, the findings may leave many oncologists feeling very uncomfortable. Although the median age for breast cancer in the United States is just short of 70 years, only 8% of those enrolled in these trials were 65 or older and only 2% were 70 years or older. Thus, the large majority of older patients were not referred for trial, did not meet eligibility criteria, or refused to participate. Prior studies had indicated that when older women were asked to participate in clinical research trials, the rate of acceding was comparable to younger patients.1,2 Accordingly, it is likely that the under representation relates more to physician referral and eligibility criteria.
A conclusion that can be drawn from the CALGB experience is that when older women meet the criteria, they are likely to achieve a treatment-related benefit. What would be useful to know, however, is what percentage of women at the age of 70 (or 80) meets these criteria? And what is the best way to treat those who don’t?
Medical oncologists need to apply the principles advanced by geriatricians. A pretreatment functional assessment that includes elements of physical and cognitive function, emotional strength and social support needs in one form or another, to be examined in prospective trials from which a performance scale developed offering predictive value with regard to clinical outcomes for older patients. CALGB and other cooperative groups, including the Geriatric Oncology Consortium (GOC) have taken on this task and, hopefully, reports of clinical trials in the future will include those high performing older individuals who are eligible for aggressive treatment regimens, but also more typical patients who are burdened with comorbidities or other functional impairments. These more typical patients are the ones we generally see in community practice and data are currently not available on how best to treat.
References
1. Kemeny MM, et al. J Clin Oncol. 2003;21:2268-2275.
2. Kornblith AB, et al. Cancer. 2002;95:989-996.
Post-surgical treatment of node-positive breast cancer with chemotherapy has been shown to reduce tumor recurrence and mortality, but the value of such therapy in geriatric populations has not been firmly established. In the current analysis of 4 large Cancer and Leukemia Group B trials spanning 25 years, there was no association between age and disease-free survival or cancer mortality. However, overall survival was significantly worse for older women, presumably from causes other than breast cancer.Subscribe Now for Access
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