Racial disparities in breast cancer mortality in a multiethnic cohort in the Southeast

Authors

  • Swann Arp Adams PhD,

    Corresponding author
    1. College of Nursing, University of South Carolina, Columbia, South Carolina
    2. Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina
    3. South Carolina Statewide Cancer Prevention and Control Program, University of South Carolina, Columbia, South Carolina
    • College of Nursing and the Department of Epidemiology and Biostatistics, Cancer Prevention and Control Program, University of South Carolina, Columbia, SC 29208

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    • Fax: (803) 576-5624

  • William M. Butler MD,

    1. South Carolina Oncology Associates, Columbia, South Carolina
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  • Jeanette Fulton MD,

    1. South Carolina Comprehensive Breast Center, Columbia, South Carolina
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  • Sue P. Heiney PhD,

    1. College of Nursing, University of South Carolina, Columbia, South Carolina
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  • Edith M. Williams PhD,

    1. Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina
    2. Institute for Partnerships to Eliminate Health Disparities, University of South Carolina, Columbia, South Carolina
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  • Alexandria F. Delage BS,

    1. Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina
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  • Leepao Khang MPH,

    1. Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina
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  • James R. Hebert ScD

    1. Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina
    2. South Carolina Statewide Cancer Prevention and Control Program, University of South Carolina, Columbia, South Carolina
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Abstract

BACKGROUND:

Although much has been done to examine those factors associated with higher mortality among African American women, there is a paucity of literature that examines disparities among rural African Americans in South Carolina. The purpose of this investigation was to examine the association of race and mortality among breast cancer patients in a large cohort residing in South Carolina for which treatment regimens are standardized for all patients.

METHODS:

Subjects included 1209 women diagnosed with breast cancer between 2000 and 2002 at a large, local hospital containing a comprehensive breast center. Kaplan-Meier survival curves were calculated to determine survival rates among African American and European American women, stratified by disease stage or other prognostic characteristics. Adjusting for various characteristics, Cox multivariate survival models were used to estimate the hazard ratio (HR).

RESULTS:

The 5-year overall all-cause mortality survival proportion was ∼78% for African American women and ∼89% for European American women, P < 0.01. In analyses of subpopulations of women with identical disease characteristics, African American women had significantly higher mortality than European American women for the same type of breast cancer disease. In multivariate models, African American women had significantly higher mortality than European American women for both breast cancer-specific death (HR, 2.41; 95% confidence interval [CI], 1.21-4.79) and all-cause mortality (HR, 1.42; 95% CI, 1.06-1.89).

CONCLUSIONS:

African American women residing in rural South Carolina had lower survival for breast cancer even after adjustment for disease-related prognostic characteristics. These findings support health interventions among African American breast cancer patients aimed at tertiary prevention strategies or further down-staging of disease at diagnosis. Cancer 2011. © 2011 American Cancer Society.

INTRODUCTION

Breast cancer is the most commonly diagnosed cancer among women and ranks second as a cause of death from cancer. The American Cancer Society estimates that 254,650 women were diagnosed with breast cancer and 41,170 women died of breast cancer in 2009.1 Unfortunately, the impact of disease is not equally distributed. It is well-documented that African American women have significantly poorer breast cancer survival compared with their European-American counterparts.2 Surveillance statistics show that African American women have an overall 10% lower incidence than do European American women, yet African American women are more likely to die of invasive breast cancer than are European American women (33.5 and 24.4 per 100,000 women, respectively).3 In addition, trends in breast cancer incidence and mortality over time evince patterns that vary markedly by ethnicity. From 1975 to 2006, Surveillance, Epidemiology, and End Results data indicate that European American women had a 16% increase in breast cancer incidence and a 28% decrease in mortality.4 Although African American women experienced a 29% increase in incidence of breast cancer, they had a 6% increase in mortality during that time.4

South Carolina has some of the largest health disparities in the nation, and the most dramatic of these are associated with elevated cancer mortality rates among African Americans.5 Statewide, breast cancer incidence rates from 1996 to 2001 have remained stable, with a somewhat higher age-adjusted incidence among European American women compared with African American women (129.8 of 100,000 and 111.6 of 100,000, respectively).6 However, in South Carolina, African American women have a 47% higher risk of death from breast cancer compared with European American women (30.6 deaths/100,000/year compared with 20.8 deaths/100,000/year).6

Plausible reasons for these existing disparities range from socioeconomic factors (eg, including access to care) to biological processes.7-16 Research conducted in South Carolina has shown that African American women typically present with aggressive tumor types more typical of those found in younger European American women.8 By contrast, other investigations have shown no mortality difference among African American and European American women participating in South Carolina's National Breast and Cervical Cancer Early Detection Program, which provides free mammograms for women meeting income eligibility requirements.17 This suggests that some of the observed mortality disparity may be explained by access to mammography screening care. In all likelihood, the root of these breast cancer disparities is multifaceted, requiring intervention on a variety of levels.

Although much has been done to identify factors associated with racial disparities, there is a paucity of literature examining breast cancer disparities among rural African Americans in South Carolina. In addition, little has been done to examine the influence of disease characteristics on these disparities. Consequently, this investigation was undertaken to examine the association of race and mortality among breast cancer patients in a large cohort residing in South Carolina.

MATERIALS AND METHODS

All data used for this analysis were collected as a part of a local hospital tumor registry system. This hospital is the largest health care provider in the Midlands of South Carolina, an area that includes about 500,000 people in the 2 counties surrounding Columbia (the state's capitol) and >900,000 in the wider Standardized Metropolitan Statistical Area that roughly corresponds to its catchment area.18 The hospital maintains a comprehensive breast center with the aim of standardizing detection, diagnosis, and treatment of all breast cancer cases. Thus we were able, in part, to account for treatment differences that might reasonably be expected to influence outcome.

All data collected by the hospital tumor registry are ultimately reported to the South Carolina Central Cancer Registry, which consistently maintains a gold-certified rating through the National Association of American Cancer Registries, indicating data of exceptionally high quality, validity, and completeness. Because all data for this analysis had been previously collected for reporting purposes and were deidentified before analyses, this investigation was granted exemption from institutional review board review.

Study Population

The study population consisted of women diagnosed with a histopathologically confirmed, first primary breast neoplasm at a large, local South Carolina hospital between 2000 and 2002. In cases of multiple observations per patient (multiple tumors diagnosed at the same time), only the tumor with the highest stage was retained for analysis. Data used for this investigation were derived only from those women with a race designation of either black or white. Other races were excluded because of low frequency count; there were only 8 women who were identified as Hispanic and 43 who identified as “other.” A total of 1209 breast cancer cases were extracted from the registry.

Covariates

By using the American Joint Committee on Cancer fifth edition criteria, stage of cancer for each patient was collapsed to create 5 mutually exclusive categories of stage 0, stage I, stage II (included A and B), stage III (included A and B), and stage IV. Elston score on a scale of 3 to 9 was determined by the pathologist based upon tumor architecture, mitotic activity, and nuclear pleomorphism. This scoring was then collapsed for analysis into 3 groups: low (Elston score 3-5), moderate (Elston score 6-7), and high (Elston score 8-9). Estrogen receptor (ER) status was categorized as positive or negative. Human epidermal growth factor receptor 2 (HER2) status was classified as positive, negative, or borderline according to the immunohistochemistry test. Insurance coverage was coded as public, private, not insured, and unknown. Public insurance coverage includes Medicaid and Medicare.

Statistical Analysis

All analyses were performed using SAS version 9.2 (SAS Institute, Cary, NC). Descriptive statistics were calculated and compared by race using either a chi-square test or t test as appropriate. Kaplan-Meier survival curves were calculated, and the log-rank test statistic was used to assess for statistical differences between race groups. Cox proportional hazards modeling was used to test the association between race and mortality (both breast cancer specific and overall) after adjusting for health care insurance and various tumor characteristics. Age was included in all Cox proportional hazards models.

Because of issues of collinearity, stage and Elston score were not included in the same Cox proportional hazards model; hence, 2 final models were created. The first excluded Elston grade and adjusted for age, insurance, cancer stage, ER, and HER2. The second model excluded cancer stage and adjusted for age, insurance, ER, Elston grade, and HER2. The proportional hazards assumption was examined visually by inspecting graphs of survival function against log survival time and in the Cox model by creating interactions of the predictors and a function of survival time. An alpha level of .05 was used to determine significance for all tests.

RESULTS

A total of 1209 breast cancer patients diagnosed between 2000 and 2002 were included in the analysis. The race distribution was 31% African American and 79% European American. The mean age for European American patients was 59 years (standard deviation [SD], 13; range, 25-92 years), and for African American patients the mean age was 55 years (SD, 13; range, 20-97 years). The majority of European American and African American women had private insurance (59.47% and 52.27%, respectively). Other demographic characteristics are displayed in Table 1.

Table 1. Characteristics of Breast Cancer Patients by Ethnicity, 2000-2002a
CharacteristicRaceP
Black, No. (%)bWhite, No. (%)b
  • Abbreviation: HER2, human epidermal growth factor receptor 2.

  • a

    Missing values were excluded.

  • b

    The terms black and white are used for disease registration purposes. For this article, they are essentially synonymous with African American and European American.

  • c

    Includes Medicare and Medicaid.

No. of patients375 (31.0)834 (69.0) 
Age   
 <40 years36 (9.6)51 (6.1)<.01
 40-49 years99 (26.4)157 (18.8) 
 50-59 years112 (29.9)237 (28.4) 
 60-69 years64 (17.1)194 (23.4) 
 ≥70 years64 (17.1)195 (23.4) 
Insurance   
 Publicc154 (41.1)288 (34.5).09
 Private196 (52.3)496 (59.5) 
 Not insured16 (4.3)26 (3.1) 
 Unknown9 (2.4)24 (2.9) 
Histology description   
 Ductal carcinoma284 (75.7)586 (70.3).03
 Lobular carcinoma18 (4.8)73 (8.8) 
 Mixed ductal and lobular10 (2.7)39 (4.7) 
 All others63 (16.8)136 (16.3) 
Behavior of cancer   
 In situ65 (17.3)155 (18.6).60
 Invasive310 (82.7)679 (81.4) 
Hormone treatment   
 Administered154 (41.1)472 (56.6)<.01
 None221 (58.9)362 (43.4) 
Cancer stage   
 065 (17.6)156 (19.1)<.01
 I97 (26.3)328 (40.1) 
 II147 (39.8)267 (32.6) 
 III33 (9.8)49 (5.9) 
 IV24 (6.5)18 (2.2) 
Elston grade   
 Low34 (14.5)158 (31.6)<.01
 Moderate69 (29.4)182 (36.4) 
 High132 (56.2)160 (32.0) 
Estrogen receptor status   
 Positive165 (58.3)520 (80.5)<.01
 Negative118 (41.7)126 (19.5) 
HER2   
 Positive35 (14.2)75 (13.4).66
 Borderline25 (10.1)69 (12.3) 
 Negative187 (75.7)415 (74.2) 

Table 2 presents the 3-year and 5-year survival proportion for breast cancer-specific and all-cause mortality among African American and European American women. Similar to statistics for statewide data, significant racial differences were observed in the overall 5-year survival proportion (∼78% for African American women and ∼89% for European American women, P < .01). No significant racial differences were evident among the different stages of disease. However, there were significant overall racial differences in survival in both low and high Elston grade populations, with the largest difference evident at 5 years. Significant racial differences in survival were also observed by ER and HER2 status. Among those who had private insurance, African American women had a significantly lower 3-year and 5-year survival proportion of all-cause mortality compared with European American women (83% vs 95%, respectively, P < .01). Interestingly, no significant differences were noted for public insurance or uninsured patients.

Table 2. Three-Year and 5-Year Survival for Breast Cancer and All-Cause Mortality by Race
VariableRaceBreast Cancer MortalityAll-Cause Mortality
No.3-Year Survival (95% CI)5-Year Survival (95% CI)PaNo.3-Year Survival (95% CI)5-Year Survival (95% CI)Pb
  • Abbreviations: AA, African American; CI, confidence interval; EA, European American; HER2, human epidermal growth factor receptor 2.

  • a

    Comparison between AA and EA among breast cancer mortality.

  • b

    Comparison between AA and EA among all-cause mortality.

  • c

    Includes Medicare and Medicaid.

OverallAA30692% (89%-95%)91% (87%-94%)<.0137586% (82%-89%)78% (73%-82%)<.01
EA71598% (97%-99%)98% (97%-99%) 83493% (91%-95%)89% (87%-91%) 
Cancer stage         
 0AA61100%98% (88%-100%).5165100%95% (86%-98%).07
 EA15199% (95%-100%)99% (95%-100%) 15699% (96%-100%)99% (96%-100%) 
 IAA78100%100%.259794% (87%-97%)84% (75%-90%).11
 EA29499% (97%-100%)99% (97%-100%) 32896% (92%-97%)92% (88%-95%) 
 IIAA12395% (89%-98%)95% (89%-98%).0514788% (82%-93%)83% (76%-88%).41
 EA21599% (95%-100%)99% (95%-100%) 26792% (88%-95%)85% (80%-89%) 
 IIIAA2568% (46%-83%)64% (42%-80%)<.013666% (49%-80%)55% (37%-69%).13
 EA3597% (15%-77%)94% (78%-98%) 4982% (68%-90%)75% (60%-87%) 
 IVAA833% (12%-56%)27% (8%-50%).191833% (16%-52%)13% (3%-29%).09
 EA1550% (15%-77%)50% (15%-77%) 2444% (22%-65%)33% (14%-55%) 
Elston grade         
 LowAA26100%100%3494% (78%-98%)78% (60%-89%)<.01
 EA142100%100% 15897% (93%-99%)96% (92%-98%) 
 ModerateAA56100%98% (88%-100%).516993% (83%-97%)87% (76%-93%).52
 EA15599% (94%-100%)99% (94%-100%) 18292% (87%-95%)88% (82%-92%) 
 HighAA10185% (76%-91%)84% (75%-90%)<.0113277% (69%-83%)69% (60%-76%).04
 EA12197% (92%-99%)97% (91%-99%) 16087% (81%-92%)80% (73%-86%) 
Estrogen receptor status       
 PositiveAA13496% (90%-98%)96% (90%-98%)<.0116590% (85%-94%)81% (74%-86%).04
 EA43999% (97%-100%)99% (97%-100%) 52090% (85%-94%)89% (86%-91%) 
 NegativeAA9282% (72%-89%)79% (68%-86%).0211872% (63%-80%)65% (56%-73%).03
 EA10393% (86%-97%)91% (83%-95%) 12686% (78%-91%)78% (70%-85%) 
HER2         
 PositiveAA3181% (62%-91%)74% (55%-86%)<.013580% (62%-90%)67% (49%-80%).03
 EA6695% (86%-98%)95% (86%-98%) 7588% (78%-93%)85% (74%-91%) 
 NegativeAA15093% (87%-96%)93% (87%-96%)<.0118784% (78%-89%)79% (72%-84%).02
 EA34699% (97%-99%)99% (97%-99%) 41593% (90%-95%)88% (78%-94%) 
 BorderlineAA1889% (62%-97%)89% (62%-97%).342584% (63%-94%)63% (41%-79%)<.01
 EA6197% (87%-99%)95% (85%-98%) 6993% (83%-97%)88% (78%-94%) 
Insurance         
 PubliccAA11191% (83%-95%)91% (83%-91%).0415482% (74%-87%)71% (63%-78%).25
 EA21196% (92%-98%)96% (92%-98%) 28886% (82%-90%)78% (73%-83%) 
 PrivateAA17492% (87%-96%)91% (86%-95%)<.0119689% (84%-93%)83% (77%-87%)<.01
 EA46199% (98%-100%)99% (98%-100%) 49697% (95%-98%)95% (93%-97%) 
 Not insuredAA1486% (54%-96%)86% (54%-96%).341681% (52%-94%)81% (52%-94%).51
 EA2295% (70%-99%)95% (70%-99%) 2688% (67%-96%)84% (62%-94%) 

As with overall survival, African American women had significantly lower breast cancer survival rates for most tumor characteristics and insurance categories. Unlike overall survival models, African American women who had public insurance were significantly more likely to die of breast cancer than European American women (91% vs 96%, P = .04).

Table 3 presents the results of several breast cancer-specific and overall survival Cox proportional hazards models. African American women had >4-fold excess risk of death from breast cancer (hazard ratio [HR], 4.49; 95% confidence interval [CI], 2.42-8.35) and about 2-fold excess risk of death from all causes (HR, 2.04; 95% CI, 1.55-2.67). After controlling for age, insurance, stage, Elston grade, ER, and HER2, African American women still had a higher risk of death from both breast cancer and all-cause mortality. Two other models were run to examine the separate effects of stage and Elston score. The first model, adjusted for age, insurance, stage, ER, and HER2, showed that African American women had >2-fold excess risk of death from breast cancer (HR, 2.41; 95% CI, 1.21-4.79) and 1.42-fold risk (95% CI, 1.06-1.89) for all-cause mortality. The second model was adjusted for age, insurance, Elston score, ER, and HER2; the HRs for breast cancer and all-cause mortality were 3.45 (95% CI, 1.79-6.65) and 1.54 (95% CI, 1.16-2.05), respectively.

Table 3. Adjusted Hazard Ratios Among African American Women Compared With European American Women for Breast Cancer-Specific and Overall Survival Deaths With Selected Characteristics Added Into the Model
VariablesaHazard Ratio for Race (95% CI)
Breast Cancer DeathsAll Deaths
  • Abbreviation: CI, confidence interval.

  • a

    All models include age.

  • b

    Adjusted for age, insurance, estrogen receptor status, human epidermal growth factor receptor 2, and stage.

  • c

    Adjusted for age, insurance, estrogen receptor status, human epidermal growth factor receptor 2, and Elston grade.

Race4.49 (2.42-8.35)2.04 (1.55-2.67)
Race, insurance4.25 (2.26-7.99)1.81 (1.37-2.39)
Race, stage2.69 (1.41-5.13)1.70 (1.29-2.24)
Race, Elston grade3.94 (2.09-7.39)1.80 (1.37-2.37)
Race, estrogen receptor status3.27 (1.70-6.18)1.79 (1.36-2.36)
Race, human epidermal growth factor receptor 24.62 (2.48-8.61)2.03 (1.55-2.67)
Final model 1b2.41 (1.21-4.79)1.42 (1.06-1.89)
Final model 2c3.45 (1.79-6.65)1.54 (1.16-2.05)

DISCUSSION

In this multiethnic cohort in South Carolina, of whom nearly ⅓ were African Americans, significant racial disparities were found in breast cancer mortality after accounting for tumor characteristics and other prognostic characteristics. After adjusting for important covariates, the excess risk of death from breast cancer in African American women was 2.41 times the risk for European American women.

Many factors may contribute to differential breast cancer prognosis for African American and European American women, including biological factors,8, 9, 14-16, 19 socioeconomic status,7, 10-13, 20 and health care access.21 Patients' refusal of therapy has also been shown to be an important contribution to breast cancer prognosis, especially for African American women.22 With this investigation, we were able to control for some aspects related to socioeconomic status and health care access by using a population of patients who received all their breast cancer care at an institution with standardized protocols to ensure standardization of the physician recommendation and receipt of different treatment regimens. Previous quality care investigations demonstrated that all breast cancer patients within this program received the recommended treatment protocol.23 Consequently, our findings suggest that some of the mortality disparities observed may be related to differences in the biological basis of disease development and progression. If this hypothesis should prove to be true upon additional investigation, future work should focus on elucidating better and more specialized treatment regimens for African American women diagnosed with breast cancer.

These findings also argue for investigation into the underlying causes of carcinogenesis that could result in health interventions among African American breast cancer patients aimed at tertiary prevention strategies or disease recurrence. For example, modification of diet and physical activity have been shown to be potentially important secondary tertiary prevention efforts.24, 25 Our previous work shows that diet and physical activity interventions can be effective in reducing body mass (and thereby, adiposity) among breast cancer survivors in the short term.26 Work from our group and others shows that adiposity, as estimated by body mass index (weight [kg]/height [m]2) can influence survival.24, 25, 27-29 There is also evidence that increased vegetable consumption postdiagnosis improves survival.24, 30, 31 Other strategies might include consistent post-treatment surveillance and approaches to strengthen self-care activities. Indeed, some psychosocial interventions that have been designed to positively impact only quality of life have been shown to affect survival.32 Very few current investigations focus on meaningfully large African American populations, so increasing representation of this high-risk group in future research is a critical need.

As with any epidemiological investigation, this study is not without its limitations. Although the hospital attempts to standardize treatment recommendations and courses for all breast cancer patients diagnosed in its system,23 individual patients may choose not to undergo a recommended treatment because of financial reasons, cultural perspective, or personal beliefs. If such choices are driven by culture, we would expect our findings to be biased. In addition, we were using data collected for vital status reporting purposes, not research, and were therefore somewhat limited in scope. Consequently, we did not have information on factors that might impact recurrence and subsequently mortality such as body mass, treatment modality, and comorbidities. Also, the only socioeconomic variable we have from the registry is health insurance; therefore, complete adjustment for socioeconomic status in our findings is somewhat limited.

Conversely, there are many strengths to this investigation that should be noted. Although cohorts have been formed to investigate racial disparities in cancer risks in underserved populations throughout the South,33 this is among the first breast cancer mortality studies to be conducted in a multiethnic cohort representing the southeastern United States. South Carolina is characterized as a largely rural state with a high representation of African American residents.18 It also has many areas that are medically underserved (including the area from which this cohort is derived). Thus, this article focuses on a population that has been chronically underrepresented in terms of both careful monitoring of services and participation in research. In addition, because of the large African American women representation and lengthy follow-up period, we had ample sample sizes and power to examine the various breast cancer subpopulations. These stratified analyses were instrumental in being able to elucidate the impact of tumor characteristics and race on mortality.

In conclusion, we found evidence for significantly poorer survival among African American breast cancer patients diagnosed with identical stage breast cancer as European American patients. Furthermore, after adjusting for multiple prognostic indicators, African American women were still more likely to die from both breast cancer and all-cause mortality compared with European American women. Evidence derived from this cohort suggests a possible biological processing basis for some of the breast cancer mortality disparities seen in South Carolina.

FUNDING SOURCES

The study was supported by the South Carolina Cancer Disparities Community Network through grant number 1 U01 CA114601-01 from the National Cancer Institute (Community Networks Program).

CONFLICT OF INTEREST DISCLOSURES

The authors made no disclosures.

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