Variation in breast cancer incidence and outcome is well-documented between geographically separated populations on a worldwide basis. Several factors contribute to these trends and observations, including lifestyle, diet, environment, culture, and genetics. The United States is characterized by a richly-diverse population with regard to ethnic/racial background as well as all of the other factors listed that account for differences in cancer burden. Disparities in breast cancer burden between ethnic/racially-delineated subsets of the American population are well-documented by the Surveillance, Epidemiology, and End Results (SEER) Program, the Centers for Disease Control (CDC) and the North American Association of Central Cancer Registries (NAACCR)(1–3).

Ward et al (1) demonstrated the expected adverse effects of poverty on cancer survival for men and women of all ethnic backgrounds, and prevalence of socioeconomic disadvantages is higher for ethnic minorities such as African Americans and Hispanic/Latino Americans. Even within discrete strata of socioeconomic status however, disparities in cancer survival are seen between communities defined by ethnic background. However as shown by Newman et al (4), breast cancer survival studies that account for socioeconomic status reveal a persistent nearly-30% higher mortality hazard for African American compared to White American patients. Disentangling the effects of race/ethnicity, culture, and socioeconomic resources on cancer risk is further confounded by the fact that we rely on self-reporting of patient race/ethnic background when in fact an individual's lineage may have included contributions from several different ancestral populations. The ethnic/racial composition of the U.S. is shifting in favor of increased diversity. An improved understanding of the multi-factorial etiology of healthcare disparities is therefore critical for improved cancer control among contemporary as well as future generations of our diverse patient population.

Clinical trials and the study of breast cancer subtypes are shedding more light on breast cancer risk as it correlates with ethnic/racial background. Among the 156,570 prospectively-followed postmenopausal participants of the Women's Health Initiative protocols followed for a median of 6.3 years, risk of being diagnosed with estrogen receptor-negative, high-grade breast cancer was nearly five time higher for African American compared to White American women (adjusted OR = 4.70, 95% CI = 3.12 to 7.09), and mortality was higher for the African American breast cancer patients as well (HR = 1.79, 95% CI = 1.05 to 3.05). Carey et al (5) analyzed immunohistochemical surrogate markers for basal breast cancer subtypes among the Carolina Breast Cancer Study dataset, and reported an increased prevalence of these more aggressive tumors among premenopausal African American women (39%) compared with postmenopausal African American women (14%) and non-African American women (16%) of any age (P<.001). Albain et al (6) reviewed the collective, organ-specific protocols of the Southwest Oncology Group (SWOG) and found that equal treatments within the context of the standardized clinical trials mechanism, except for the hormonally-driven cancers such as breast and prostate. For these cancer sites, significantly worse outcomes were observed for the African American clinical trial participants. The triple-negative molecular marker status has become a common clinical surrogate to identify the basal breast cancer subtype, and several population-based as well as single institution studies have now documented an approximately two-fold higher risk of triple-negative breast cancer among African American compared to White American women. Furthermore, an expanding database of international breast cancer studies are now revealing even higher risk of triple-negative breast cancers among western sub-Saharan African women.

It is possible that use of genotyping technology will refine studies of cancer risk related to ancestral heritage. Use of Ancestry Informative Markers (AIMs), also called Ethnic Difference Markers, may provide a more objective strategy for defining and quantifying racial/ethnic background. These AIMs can estimate the extent of an individual's West African, European, Native American, East Asian, and South Asian ancestry (7–17). Ongoing studies seek to evaluate the optimal genetic patterns and markers for these types of association studies.

This presentation will include preliminary findings from an ongoing international collaboration between the University of Michigan and the Komfo Anoyke Teaching Hospital in Kumasi, Ghana. This research partnership involves the study of breast disease patterns and molecular markers in western, sub-Saharan Africans compared with those of African Americans and White Americans. This collaborative effort has demonstrated a correlation between frequency of high-risk/triple-negative breast cancer and presumed extent of African ancestry (18), and it has also served as a model for establishing other international oncology research programs. (19, 20)

References

1. Ward E, Jemal A, Cokkinides V, Singh G, Cardinez C, Ghafoor A, et al. Cancer disparities by race/ethnicity and socioeconomic status. CA Cancer J Clin 2004;54(2):78-93.

2. Edwards BK, Brown ML, Wingo PA, Howe HL, Ward E, Ries LA, et al. Annual report to the nation on the status of cancer, 1975–2002, featuring population-based trends in cancer treatment. J Natl Cancer Inst 2005;97(19):1407-27.

3. Howe HL, Wu X, Ries LA, Cokkinides V, Ahmed F, Jemal A, et al. Annual report to the nation on the status of cancer, 1975–2003, featuring cancer among U.S. Hispanic/Latino populations. Cancer 2006;107(8):1711-42.

4. Newman LA, Griffith KA, Jatoi I, Simon MS, Crowe JP, Colditz GA. Meta-analysis of survival in African American and white American patients with breast cancer: ethnicity compared with socioeconomic status. J Clin Oncol 2006;24(9):1342-9.

5. Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, et al. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. Jama 2006;295(21):2492-502.

6. Albain KS, Unger JM, Crowley JJ, Coltman CA, Jr., Hershman DL. Racial disparities in cancer survival among randomized clinical trials patients of the Southwest Oncology Group. J Natl Cancer Inst 2009;101(14):984-92.

7. Zhang C, Chen K, Seldin MF, Li H. A hidden Markov modeling approach for admixture mapping based on case-control data. Genet Epidemiol 2004;27(3):225-39.

8. Tian C, Hinds DA, Shigeta R, Kittles R, Ballinger DG, Seldin MF. A genomewide single-nucleotide-polymorphism panel with high ancestry information for African American admixture mapping. Am J Hum Genet 2006;79(4):640-9.

9. Keita SO, Kittles RA, Royal CD, Bonney GE, Furbert-Harris P, Dunston GM, et al. Conceptualizing human variation. Nat Genet 2004;36(11 Suppl):S17-20.

10. Smith MW, Lautenberger JA, Shin HD, Chretien JP, Shrestha S, Gilbert DA, et al. Markers for mapping by admixture linkage disequilibrium in African American and Hispanic populations. Am J Hum Genet 2001;69(5):1080-94.

11. Smith M. A high-density admixture map for gene discovery in African Americans. American Journal of Human Genetics 2004;74:1001-13.

12. Collins-Schramm HE, Kittles RA, Operario DJ, Weber JL, Criswell LA, Cooper RS, et al. Markers that discriminate between European and African ancestry show limited variation within Africa. Hum Genet 2002;111(6):566-9.

13. Collins-Schramm HE, Phillips CM, Operario DJ, Lee JS, Weber JL, Hanson RL, et al. Ethnic-difference markers for use in mapping by admixture linkage disequilibrium. Am J Hum Genet 2002;70(3):737-50.

14. Burchard EG, Ziv E, Coyle N, Gomez SL, Tang H, Karter AJ, et al. The importance of race and ethnic background in biomedical research and clinical practice. N Engl J Med 2003;348(12):1170-5.

15. Yang BZ, Zhao H, Kranzler HR, Gelernter J. Characterization of a likelihood based method and effects of markers informativeness in evaluation of admixture and population group assignment. BMC Genet 2005;6:50.

16. Yang N. Examination of ancestry and ethnic affiliation using highly informative diallelic DNA markers: Application to diverse and admixed populations and implications for clinical epidemiology and forensic medicine. Human Genetics 2005;118:382-92.

17. Burchard E. Latino populations: A unique opportunity for the study of race, genetics, and social environment in epidemiological research. American Journal of Public Health 2005;95:2161-68.

18. Stark A, Kleer CG, Martin I, Awuah B, Nsiah-Asare A, Takyi V, et al. African ancestry and higher prevalence of triple-negative breast cancer: findings from an international study. Cancer 2010;116(21):4926-32.

19. Martin IK, Awuah B, Newman LA. Guide for investigators conducting international cancer research involving developing nations. Cancer;116(6):1396-9.

20. Awuah B, Martin IK, Takyi V, Kleer C, Nsiah-Asare A, Aitpillah F, et al. Implementation of a percutaneous core needle biopsy training program: results from the university of michigan-komfo anokye teaching hospital breast cancer research partnership. Ann Surg Oncol;18(4):957-60.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):PL03-03.