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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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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 Cook County Hospital experience 1973-1987. Cancer 1990;65:1062-71. Abstract.

Boyer-Chammard A, Taylor TH, Anton-Culver H. Survival differences in breast cancer among racial/ethnic groups: a population-based study. Cancer Detect Prev 1999;23:463-73. 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.

Dignam JJ, Redmond CK, Fisher B, Costantino JP, Edwards BK. Prognosis among African-American women and white women with lymph node negative breast carcinoma: findings from two randomized clinical trials of the National Surgical Adjuvant Breast and Bowel Project (NSABP). Cancer 1997;80:80-90. 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. J Natl Cancer Inst 1994;86:705-12. Abstract.

Greenlee RT, Murray T, Bolden S, Wingo PA. Cancer statistics, 2000. CA Cancer J Clin 2000;50:7-33. Abstract.

Heimann R, Ferguson D, Powers C, Suri D, Weichselbaum RR, Hellman S. Race and clinical outcome in breast cancer in a series with long-term follow-up evaluation. J Clin Oncol 1997;15:2329-37. Abstract.

McCaskill-Stevens W, Bryant J, Costantino J, Wickerham DL, Vogel V, Wolmark N. Incidence of contralateral breast cancer (CBC), endometrial cancer (EC), and thromboembolic events (TE) in African American (AA) women receiving tamoxifen for treatment of primary breast cancer. [abstract]. Proc Am Soc Clin Oncol 2000. Abstract.

Muss HB, Hunter CP, Wesley M, Correa P, Chen VW, Greenberg RS, et al. Treatment plans for black and white women with stage II node-positive breast cancer: The National Cancer Institute Black/White Cancer Survival Study experience. J Natl Cancer Inst 1992;70:2460-7. Abstract.

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Yeap BY, Zelen M. Minority differences in cancer survival on cooperative clinical trials. [abstract]. Proc Am Soc Clin Oncol 2000. Abstract.

Yood MU, Johnson CC, Blount A, Abrams J, Wolman E, McCarthy BD, et al. Race and differences in breast cancer survival in a managed care population. J Natl Cancer Inst 1999;91:1487-91. Abstract.