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Factors Used To Select Adjuvant Therapy: An Overview of Age and Race

Hyman B. Muss, M.D.

Age, race, and socioeconomic status all play a role in decisions about adjuvant therapy for breast cancer. Age is important for two major reasons: first, because it remains the major risk factor for breast cancer; and second, because the potential benefits of adjuvant therapy diminish as competing causes of mortality (comorbidity) increase. More than half of all new breast cancers in the United States occur in women 65 and older, a statistic that has strong meaning in a population whose longevity is increasing (Yancik, 1997). In addition, comorbidity significantly increases with increasing age, and comorbidity has a major effect on patient survival (Fleming, Rastogi, Dmitrienko, et al., 1999). Race is especially important because breast cancer mortality is higher in African Americans than in white Americans. Such differences are related to several factors, including stage at presentation, tumor biology, and sociodemographic characteristics (Eley, Hill, Chen, et al., 1994).

Compelling data from a worldwide meta-analysis of adjuvant therapy showed that for older patients with estrogen receptor (ER) or progesterone receptor (PR) positive tumors, tamoxifen significantly increased both the amount of time free from relapse and time of overall survival (EBCTCG, 1998a). Women 70 years and older who took 5 years of tamoxifen had a 54 percent decrease in the annual odds of breast cancer recurrence and a 34 percent decrease in the annual odds of dying of breast cancer. Chemotherapy alone has not been adequately studied in older patients, and in the same overview less than 700 women 70 years and older were entered on randomized trials. Chemotherapy is associated with significant improvements in both relapse-free and overall survival in women ages 50 to 69 years (20.3 percent and 11.3 percent reduction in annual odds of relapse and death, respectively) (EBCTCG, 1998b), but further trials are needed that factor in the effects of comorbidity on treatment outcome, treatment-related toxicity, and quality of life for older women. The potential benefits of adjuvant therapy in older women have recently been estimated using a mathematical model (Extermann, Balducci, Lyman, 2000); it is clear that the value of adjuvant therapy diminishes substantially as age and comorbidity increase, and as non-breast-cancer-related illness becomes a major competing cause of death. What also seems clear is that older women in good general health tolerate standard chemotherapy regimens almost as well as younger women (Christman, Muss, Case, et al., 1992). In the absence of a trial, the recommendations for adjuvant therapy made by an international consensus panel appear prudent and should be used as a treatment guideline (Goldhirsch, Glick, Gelber, et al., 1998). Future clinical research in this setting should focus on adjuvant trials directed at older patients. In addition to relapse-free and overall survival, these trials should have quality of life, functional status, and comorbidity assessment as key endpoints.

African Americans and other minorities are frequently underrepresented in adjuvant trials but available data suggest that, at least for African Americans, the benefits of therapy are similar to those for white women when outcomes are adjusted for stage, comorbid illness, and pathologic and sociodemographic variables (Dignam, 2000). Of note, many trials have shown small but potentially important biological differences in breast cancer between African American and white patients. African American patients are more likely than whites to have more biologically aggressive, hormone receptor (HR) negative tumors that may limit the potential life-prolonging benefits of tamoxifen therapy (or ovarian ablation) (Elledge, Clark, Chamness, et al., 1994). In large numbers of patients these small differences in tumor biology may prove to be highly meaningful. Little data are available on Hispanic patients and other minorities concerning the risks and benefits of adjuvant therapy. Available data suggests that Hispanic patients with early breast cancer have a prognosis that lies between those for African American and white patients (Elledge, Clark, Chamness, et al., 1994). The data also suggest that for Hispanics, as for African Americans, socioeconomic factors play a key role in the outcome (Franzini, Williams, Franklin, et al., 1997). A key concern for African American patients and other minorities is access to high quality care, including clinical trials. Major efforts by the NCI and other organizations to improve access of minorities to clinical trials are underway. Poverty is associated with poorer cancer outcomes for all Americans irrespective of racial or ethnic group, and remains a national issue (McWhorter, Schatzkin, Horm, et al., 1989).

References

Christman K, Muss HB, Case LD, Stanley V. Chemotherapy of metastatic breast cancer in the elderly. The Piedmont Oncology Association experience [see comment]. JAMA 1992;268:57-62. Dignam JJ. Differences in breast cancer prognosis among African American and Caucasian women. CA Cancer J Clin 2000;50:50-64. Abstract.

Dignam JJ. Differences in breast cancer prognosis among African American and Caucasian women. CA Cancer J Clin 2000;50:50-64. Abstract.

Early Breast Cancer Trialists’ Collaborative Group. Tamoxifen for early breast cancer: an overview of the randomized trials [see comments]. Lancet 1998a;351:1451-67. Abstract.

Early Breast Cancer Trialists’ Collaborative Group. Polychemotherapy for early breast cancer: an overview of the randomized trials. Lancet 1998b;352:930-42. Abstract.

Eley JW, Hill HA, Chen VW, Austin DF, Wesley MN, Muss HB, et al. Racial differences in survival from breast cancer. Results of the National Cancer Institute Black/White Cancer Survival Study. JAMA 1994;272:947-54. Abstract.

Elledge RM, Clark GM, Chamness GC, Osborne CK. Tumor biologic factors and breast cancer prognosis among white, Hispanic, and black women in the United States [see comments]. J Natl Cancer Inst 1994;86:705-12. Abstract.

Extermann M, Balducci L, Lyman GH. What threshold for adjuvant therapy in older breast cancer patients? J Clin Oncol 2000;18:1709-17. Abstract.

Fleming ST, Rastogi A, Dmitrienko A, Johnson KD. A comprehensive prognostic index to predict survival based on multiple comorbidities: a focus on breast cancer. Med Care 1999;37:601-14. Abstract.

Franzini L, Williams AF, Franklin J, Singletary SE, Theriault RL. Effects of race and socioeconomic status on survival of 1,332 black, Hispanic, and white women with breast cancer [see comments]. Ann Surg Oncol 1997;4:111-8. Abstract.

Goldhirsch A, Glick JH, Gelber RD, Senn HJ. Meeting highlights: international consensus panel on the treatment of primary breast cancer [see comments]. J Natl Cancer Inst 1998;90:1601-8. No Abstract Available.

McWhorter WP, Schatzkin AG, Horm JW, Brown CC. Contribution of socioeconomic status to black/white differences in cancer incidence. Cancer 1989;63:982-7. Abstract.

Yancik R. Cancer burden in the aged: an epidemiologic and demographic overview. Cancer 1997;80:1273-83. Abstract.