Abstract PL03-03: High-risk/triple-negative breast cancer and African ancestry

Abstract

Abstract 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)