Cancer in the oldest old: Making better treatment decisions

Cancer incidence and mortality risk increase dramatically with advancing age. Telomere shortening and alterations in tumor suppressor gene activity with biologic aging contribute to cancer risk for individuals who live longer. In the United States, the median age at cancer diagnosis is 67 years and the median age at cancer death is 73 years. There were 1,479,350 new cancer cases and 562,340 deaths projected in the United States for 2009. Presently, approximately 25% of new cancer diagnoses are in patients 65 to 74 years, approximately 22% in patients 75 to 84 years, and about 7.5% in those 85 years or older. Although overall mortality risk from cancer is decreasing, these trends are not as evident for patients age 75 or older. Population dynamics are also increasing the importance of geriatric oncology. Populations in developed countries are aging rapidly, with predictable effects on health care demands. The size of the United States population age 65 or older will double between 2000 and 2030. This, coupled with the fact that the life expectancy for a 65-year-old woman is 20 additional years and for a 75-year-old woman is 12.8 additional years, will result in a dramatic increase in cancer in the older population. When compared with younger patients with cancer, older patients have consistently received less screening, less aggressive surgery, and less systemic therapy. However, little descriptive research and fewer therapeutic trials provide the evidence needed to guide screening and treatment decisions. Two studies in this issue of Journal of Clinical Oncology (JCO) focus on issues in elders. Schonberg and colleagues used the linked Surveillance, Epidemiology and End Results–Medicare data set of 49,616 patients with stage I/II breast cancer to describe characteristics, treatment, and survival in women 80 years or older—the “oldestold.” Certainly their analysis is timely and pertinent. In women, breast cancer is the most common cause of cancer and occurs in approximately 13% of women during their lifetime. It is the second leading cause of cancer death (after lung cancer) and is responsible for approximately 40,000 deaths yearly. Both breast cancer incidence and mortality rise dramatically with age. On the positive side, major advances in screening and treatment have led to declines in the mortality rate. Older patients tend to have a less aggressive tumor biology and are more likely to be lower in grade, hormone receptor–positive, HER2-negative, and node-negative than tumors in younger women. With the exception of the very old and very young, and when adjusted for breast cancer stage, differences in tumor biology appear to have minimal impact and older and younger women have similar breast cancer–specific survival. Unfortunately, the elderly are not always offered the latest treatments—although the selection criteria remain unclear, and the benefits and risks of this modified treatment approach remain controversial. In the Schonberg et al study, a comparison group of “younger women” were defined as those 67 to 79 years (welcome news for many of us) so Medicare treatment data could be linked to Surveillance, Epidemiology and End Results data. A strength of this study is the investigators’ decision to retain and impute stage for subjects without histology or staging—data that may be absent in clinical practice when diagnostic work-up is curtailed. Comparing women 80 years or older with those 67 to 79 years likely explains why no major difference in tumor characteristics were found in these two groups. Schonberg and colleagues found a significantly higher risk of dying of breast cancer after age 80 and that treatment was significantly related to age and comorbidity with age as the stronger predictor—the older you are, the less treatment you get. With a median follow-up of 5.6 years, and adjusting for treatment, comorbidity, and other factors, only 4.5% of women with stage I and 16.1% of those with stage II breast cancer died of breast cancer causes while the majority of patients died of nonbreast cancer causes. The risk of death from other causes was higher for all age and tumor risk groups. Among women with hormone receptor–negative, node-positive tumors, a group with high recurrence risk and greater benefit from chemotherapy, women 67 to 79 years treated with chemotherapy had a significant reduction in breast cancer mortality compared with women not given chemotherapy. The authors found a trend for poorer survival in women 80 or older who received chemotherapy. This may have been due to more aggressive tumors or increased treatment toxicity in the treated group. Because of the descriptive and retrospective nature of this study, unmeasured variables, such as cognitive function, performance status, and patient preferences may confound the reported relationships. Still, the data from this analysis are important and suggest areas where clinical trials might be most helpful, such as defining the role of chemotherapy and its potential toxicity in women older than 80 years with hormone receptor–negative tumors. As people age, they become biologically more heterogeneous. Genetic risks are fully expressed, and environmental exposures and injuries test physiologic reserves. While chronic illnesses and functional dependency become more common, there are also increasing numbers of highly functional octogenarians. Understanding these variations in organ function, cognitive reserve, and functional status, as well as social and emotional resources, is essential to optimize choices about screening and cancer treatment. Geriatricians use comprehensive assessments of medical, functional, cognitive, pharmacologic, nutritional, and social domains to develop treatment plans and reduce iatrogenic risks for older patients. This approach is clinically valid, but time consuming. Luciani and colleagues studied the accuracy of the Vulnerable Elders Survey (VES-13), a self-report functional screen that is predictive of 2-year mortality, to detect problems Editorials