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Educational Supplement: Appendix
Racial/Ethnic
Background and Benefits of Adjuvant Therapy for Breast Cancer
James
J. Dignam, Ph.D.
Variation in
breast cancer survival by racial/ethnic background has been noted
in many studies, as well as in summaries of national cancer statistics
(Greenlee, Murray, Bolden, et al., 2000). Numerous factors have
been implicated as sources of these differences, including clinical
and pathologic features of the disease indicative of poor prognosis,
economic resource inequities and other social factors, and disparities
in treatment access and (possibly) efficacy. After a brief review
of these factors, we examine the available data from randomized
clinical trials, where disease stage is comparable and treatments
are uniformly delivered. We also consider studies conducted in settings
where uniformity of disease diagnosis and care can be reasonably
assumed. Using this information, we address (1) whether outcomes
among women of different racial origins are more similar within
these settings than outcomes observed in the population at large,
and (2) whether there is evidence of differential efficacy of adjuvant
therapy according to race.
Disparity in
breast cancer prognosis between African Americans and Caucasians
has been attributed to clinical and demographic characteristics,
pathologic and biologic disease features, and socioeconomic status
and related health care factors (Dignam, 2000). African American
women are more often diagnosed at a later stage of the cancer, tend
to be younger at diagnosis, and more often exhibit less favorable
tumor characteristics. Several studies also have found disparities
in health care, including less frequent administration of care in
accordance with established guidelines. Limited studies of Asian
Americans, who tend to have a lower incidence of breast cancer,
indicate equal or better prognosis than that of whites, in part
due to earlier stage at diagnosis and favorable disease features
(Boyer-Chammard, Taylor, Anton-Culver, 1999). Studies of Hispanic
women have generally found the prevalence of poor prognosis indicators
to be intermediate between those of blacks and whites (Elledge,
Clark, Chamness, et al., 1994). In general, survival comparisons
among women whose cancer is at a comparable stage from any racial
background are considerably more similar than those seen when overall
rates are compared, but some residual disparities remain.
Among the major
studies addressing disparities between blacks and whites, it has
been found, in most cases, that a primary explanatory factor, such
as disease stage at diagnosis, does not fully account for the difference
between the groups, but when additional factors are taken into account
the outcomes are similar. Results derived among patients participating
in randomized clinical trials are particularly illustrative of this
point. The Cancer and Leukemia Group B (CALGB) study compared characteristics
and outcomes for blacks and whites participating in a trial of adjuvant
chemotherapy for node-positive breast cancer (Roach, Cirrincione,
Budman, et al., 1997). The authors found blacks to be younger at
diagnosis and to have larger tumors that were more often estrogen
receptor (ER)-negative. Excess risk of death among blacks relative
to whites (and others) was reduced from 35 percent to 14 percent
after taking into account these prognostic factor differences. Excess
risk of recurrence or death for blacks was reduced from 24 percent
to 7 percent. Recently, analyses of outcomes among African Americans
and Caucasians participating in studies of the Eastern Cooperative
Oncology Group (ECOG) were presented (Yeap, Zelen, 2000). In that
study, black women participating in ECOG adjuvant breast cancer
trials between 1983 and 1995, matched with white women of similar
age, treating institution, and treatment arm, had comparable survival
outcomes. Estimates of treatment effects within race groups were
not presented in these studies, and such analyses are generally
not warranted unless there is statistical evidence of differential
treatment efficacy (e.g., interactions) between race and treatment
group. Furthermore, such analyses are hindered by low statistical
power.
Previously published
results from two National Surgical Adjuvant Breast and Bowel Project
(NSABP) trials similarly indicated that when stage of disease and
treatment are comparable, outcomes for African Americans and Caucasians
do not differ markedly (Dignam, Redmond, Fisher, et al., 1997).
In that study we focused on patients with node-negative breast cancer
and examined outcomes separately by ER status, which has been implicated
as an important explanatory factor in disparities between these
groups. Results indicated equal disease recurrence risk and statistically
nonsignificant 10 percent excess in mortality for blacks after adjustment
for prognostic factors. Among women with ER-negative tumors receiving
chemotherapy, a reduction in disease-free survival (DFS) events
of 32 percent was noted among blacks, compared to 36 percent for
whites. Among patients with ER-positive tumors receiving tamoxifen,
reductions in DFS events were 20 percent for blacks and 39 percent
for whites. Statistical evidence of a differential treatment response
by race was not noted. This latter finding is further supported
by a recent study finding a comparable reduction in contralateral
breast cancer incidence among African American and Caucasian patients
receiving tamoxifen in NSABP breast cancer treatment trials (McCaskill-Stevens,
Bryant, Costantino, et al., 2000). Newly examined data from NSABP
trials among node-positive patients have also shown comparable prognosis
and extent of treatment benefit among black and white participants.
Observational
retrospective studies evaluating outcomes in health care systems
where treatment is uniform have been presented as evidence of the
efficacy of established treatment regimens among minority patient
populations (Briele, Walker, Wild, et al., 1990; Heimann, Ferguson,
Powers, et al., 1997; Yood, Johnson, Blount, et al., 1999). As in
clinical trials, results of these studies suggest that, for patients
treated in accordance with recommendations for their clinical and
pathologic disease presentation, outcomes and extent of benefit
among African Americans and Caucasians are comparable. Studies of
treatment patterns in these settings can also serve to evaluate
the extent to which current treatment guidelines are observed in
certain patient populations (Muss, Hunter, Wesley, et al., 1992;
Breen, Wesley, Merrill, et al., 1999).
In summary,
women of different race backgrounds, diagnosed at comparable disease
stage and appropriately treated, tend to experience similar breast
cancer prognosis. From the clinical trial data and studies from
equal-care settings, it may be indirectly inferred that treatment
benefits are comparable across race groups. However, important clinical
and pathologic disease characteristics may place certain women at
increased risk of poor outcome, and warrant continued study as to
how and why these may be related to race. Although demographic classification
in National Cancer Institute-sponsored clinical trials has been
found to be generally representative of the incident cancer burden
in the population (Tejeda, Green, Trimble, et al., 1996), increased
racial/ethnic diversity in clinical trial participation would be
beneficial. More diverse participation will ensure dissemination
of quality care in accordance with current treatment guidelines
and will provide the necessary data for future investigations of
the role of race in breast cancer treatment.
References
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MN, Merrill RM, Johnson K. The relationship of socio-economic status
and access to minimum expected therapy among female breast cancer
patients in the National Cancer Institute Black-White Cancer Survival
Study. Ethn Dis 1999;9:111-25. Abstract.
Briele HA Jr,
Walker MJ, Wild L, Wood DK, Greager JA, Schneebaum S, et al. Results
of treatment of stage I-III breast cancer in black Americans. The
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A, Taylor TH, Anton-Culver H. Survival differences in breast cancer
among racial/ethnic groups: a population-based study. Cancer Detect
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Dignam JJ. Differences in breast cancer prognosis among African-American
and Caucasian women. CA Cancer J Clin 2000;50:50-64. Abstract.
Dignam JJ, Redmond
CK, Fisher B, Costantino JP, Edwards BK. Prognosis among African-American
women and white women with lymph node negative breast carcinoma:
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Adjuvant Breast and Bowel Project (NSABP). Cancer 1997;80:80-90.
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Elledge RM,
Clark GM, Chamness GC, Osborne CK. Tumor biologic factors and breast
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Greenlee RT,
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D, Powers C, Suri D, Weichselbaum RR, Hellman S. Race and clinical
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McCaskill-Stevens
W, Bryant J, Costantino J, Wickerham DL, Vogel V, Wolmark N. Incidence
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thromboembolic events (TE) in African American (AA) women receiving
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Muss HB, Hunter
CP, Wesley M, Correa P, Chen VW, Greenberg RS, et al. Treatment
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Roach M 3rd,
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Tejeda HA, Green
SB, Trimble EL, Ford L, High JL, Ungerleider RS, et al. Representation
of African-Americans, Hispanics, and whites in National Cancer Institute
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