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Treating Breast Cancer: The Age Old Dilemma of Old Age

Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC

Women 65 years or older (hereafter referred to as older women) constitute half of the new breast cancer patients each year, and the absolute number of patients will double by 2030 with the "graying of America." Despite their large numbers, over the past several decades, when older women develop breast cancer, they fail to receive care consistent with prevailing guidelines.^1,2 Reasons for the divergence of care from professional recommendations may be partially explained by the lack of clinical trial data for this age group, uncertainty about the balance of treatment toxicity and benefits, differential access, the potential for therapy to amplify pre-existing medical conditions, and the effects of competing noncancer causes of mortality. There is also minimal data on older women's preferences for treatment and its outcomes.³

In this issue of the Journal of Clinical Oncology, Enger et al⁴ use a population of older women from a well-defined managed care research network to underscore the fact that, whatever the reason, increasing age was associated with receipt of nonstandard breast cancer care in the early 1990s, even after considering comorbidity, tumor factors, and other variables. Most prior studies on this topic have been performed using the Surveillance, Epidemiology, and End Results (SEER) and SEER-Medicare databases¹ and convenience cohorts.² This new study is unique in that it draws the same conclusion among women cared for in large equal-access systems. This work was facilitated by the development of the Cancer Research Network, a National Cancer Institute–funded collaboration between 12 large, mature managed care systems, including Group Health Cooperative, the Harvard Pilgrim Health Plan, Henry Ford Health Systems, Fallon Community Health Plan, and Kaiser Permanente in six regions.⁵ Managed care research networks have several potential advantages for studying the quality of cancer care. First, access is removed from the equation in examining age and other disparities. Second, they include large proportions of the population from almost all regions of the United States, providing an alternative universe for population-based studies. Third, the availability of computerized administrative databases linked to laboratory and pathology data and often electronic medical records provides more comprehensive, cost-efficient clinical data than the data available in SEER or Medicare claims.

Regardless of setting, this study joins a large body of literature that suggests that age bias plays a significant role in the persistent undertreatment of older women over time. For instance, older women who perceive more ageism in their interactions with providers are less likely to receive radiation or chemotherapy.⁶ What are the implications of such bias and potential undertreatment of older women? One immediate consequence of omission of radiation may be the potential for older women to develop recurrences later in life when they may be less able to withstand intervention. This concern may be ameliorated by use of hormonal therapy among the women who are estrogen receptor positive and have small tumors because results of a recent clinical trial and a large observational study suggest that radiation may be omitted in this group.^7,8

Omission of chemotherapy may have more serious consequences in terms of survival, especially among women with positive nodes and/or negative hormonal receptors. In juggling decisions about chemotherapy, clinicians and their patients are hampered by lack of clinical trial data. However, a recent analysis carried out by the Cancer and Leukemia Group B of four randomized clinical trials by Muss et al⁹ demonstrated that the older women healthy enough to enter a clinical trial derived the same benefit from the regimens containing chemotherapy as did younger women. In contrast, outside of the trial setting, studies using SEER-Medicare data find significant reductions in the hazards of death from all causes for older women up to age 69 years (hazard ratio = 0.70; 95% CI, 0.57 to 0.88). However, they find that the average reduction in mortality is not significant for women aged 70 years and older.¹⁰

All of these studies of older women treat age as a one-dimensional construct, virtually ignoring the considerable within-age heterogeneity in organ reserve, functional ability, frailty, and ability to tolerate various cancer treatments (physiologic age). For instance, a 70-year-old woman in the lowest quartile of health has a 9-year life expectancy, whereas a 79-year-old woman in the top quartile has a 14.6-year life expectancy. Thus, it seems reasonable that the 79-year-old woman who is in good health stands to gain significantly more from undergoing chemotherapy than the 70-year-old woman in poor health. In addition, if women's preferences are considered, even the 70-year-old woman in poor health may choose to accept the risk of chemotherapy-related adverse effects for a reasonable benefit. In our work with older women, we have found that 33% would chose chemotherapy if it would extend their lives by 12 or more months.

In addition to targeting treatment based on physiological age, quality of care for this age group would be advanced by developing a better understanding of the biology of breast cancer in older hosts. Some data suggest that the disease is less virulent in old age, but other studies show as much variability in biology across as within age groups. Unfortunately, recent research on genetic profiling has not included older women,¹¹ leaving us without the potential for better prognostication and choice of therapy.

At this time, we do not need more research to document what we already know: older women get less intensive treatment. What we need is an understanding of the biology of cancer in this population, tools that can help clinicians identify physiological reserve and ability to withstand the rigors of more aggressive treatment, and more consistent elicitation of women's informed preferences.

Author's Disclosures of Potential Conflicts of Interest

The author indicated no potential conflicts of interest.

REFERENCES

1. Nattinger AB, Gottlieb MS, Veum J, et al: Geographic variation in the use of breast-conserving treatment for breast cancer. N Engl J Med 326:1102-1107, 1992[Abstract]

2. Mandelblatt J, Yabroff KR, Kerner JF: Equitable access to cancer services: A review of barriers to quality care. Cancer 86:2378-2390, 1999[CrossRef][Medline]

3. Figueiredo MI, Cullen J, Hwang YT, et al: Breast cancer treatment in older women: Does getting what you want improve your long-term body image and mental health? J Clin Oncol 22:4002-4009, 2004[Abstract/Free Full Text]

4. Enger SM, Thwin SS, Buist DSM, et al: Breast cancer treatment among older women in integrated health care settings. J Clin Oncol 24:4377-4383, 2006

5. Wagner E, Greene S, Hart G, et al: Building a research consortium of large health systems: The cancer research network. J Natl Cancer Inst Monogr 35:3-11, 2005[Medline]

6. Mandelblatt J, Kerner J, Hadley J, et al: Variations in breast cancer treatment in older Medicare beneficiaries: Is it black or white? Cancer 95:1401-1414, 2002[CrossRef][Medline]

7. Smith BD, Gross CP, Smith GL, et al: Effectiveness of radiation therapy for older women with early breast cancer. J Natl Cancer Inst 98:681-690, 2006[Abstract/Free Full Text]

8. Hughes KS, Schnaper LA, Berry D, et al: Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer. N Engl J Med 351:971-977, 2004[Abstract/Free Full Text]

9. Muss HB, Woolf S, Berry D, et al: Adjuvant chemotherapy in older and younger women with lymph node-positive breast cancer. JAMA 293:1073-1081, 2005[Abstract/Free Full Text]

10. Du X, Goodwin JS: Patterns of use of chemotherapy for breast cancer in older women: Findings from Medicare claims data. J Clin Oncol 19:1455-1461, 2001[Abstract/Free Full Text]

11. van de Vijver MJ, He YD, van't Veer LJ, et al: A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 347:1999-2009, 2002[Abstract/Free Full Text]

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