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Educational Supplement: Appendix
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.
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