NCI Summit on Cancer Disparities: Workshop on Ancestry Informative Markers Panelists and Agenda 3:15-3:40: 3:40: Lisa Newman, MD, MPH: Univ. of Michigan Cancer Disparities and Racial/Ethnic Background: The Need for More Objective Definitions 3:40-4:10: 4:10: Jill Barnholtz-Sloan, PhD: Case-Western Comprehensive Cancer Center Using ancestry estimates as tools to better understand group or individual differences in disease risk/outcomes 4:10-4:30: 4:30: Open Discussion; Question and Answers for Dr. Barnholtz-Sloan 4:30-5:00: Closing Comments and Discussion: Dr. Worta McCaskill-Stevens: Disparities Research and the Minority-Based CCOPs
NCI Summit on Cancer Disparities DEFINING RACE/ETHNIC BACKGROUND IN STUDIES OF DISPARITIES Lisa A. Newman, M.D., M.P.H., F.A.C.S. Associate Professor of Surgery Director, Breast Care Center University of Michigan Ann Arbor, MI
Cancer Incidence & Mortality, By Race/Ethnicity Prostate Hispanic American Indian/Alaskan Native As ian/pacific Is lander African Am erican White American ************************************************* Lung & Bronchus Hispanic American Indian/Alaskan Native As ian/pacific Is lander African Am erican White American ************************************************* Colon & Rectum Hispanic Mortality Incidence American Indian/Alaskan Native As ian/pacific Is lander African Am erican White American ************************************************* Breast (Female) Hispanic American Indian/Alaskan Native As ian/pacific Is lander African Am erican White American 0 50 100 150 200 250 300 Rate, per 100,000
ETIOLOGY OF DISPARITIES IN CANCER OUTCOME Socioeconomic Resources Socioeconomic Resources Socioeconomic Resources Delivery of Care Tumor biology Genetics Lifestyle & Reproductive Experiences Environmental exposures Diet/Nutrition
Ethnicity and SES 40% 35% 30% 25% 20% 15% 10% 5% 0% White American African American Am Ind/Alask Nat <Poverty Level Uninsured
Cancer Survival and Income/SES
Cancer Disparities Are they all the same? Can clinical trial data correct for confounding effects of SES and delivery of care on ethnicityrelated outcome disparities? Unger et al: ASCO 2004- Pooled analyses of SWOG adjuvant therapy trials Outcome comparable for all ethnic groups with all cancers except African Americans with hormonallydriven cancers (breast & prostate) Various issues may contribute in different proportions to organ-site-specific cancer disparities
BREAST CANCER: A GLOBAL PERSPECTIVE U.S.A. 21.2 91.4 Nigeria 13.2 29 Ghana 11.3 24.8 France 21.4 83.2 Spain 18.1 47.9 Italy 20.7 64.9 Sweden 17.5 81 Hong Kong 9.3 34.4 China 4.5 16.4 Mortality Incidence Argentina 21.6 64.7 Less Developed Countries 9.1 23.1 Developed Countries 18.6 63.2
BREAST CA INCIDENCE & MORTALITY Age-Adjusted Rates (per 100,000 pop n) Mortality Incidence Hispanics Native Amer/Alaskan Nat Asian/Pacific Islander Black White All 0 20 40 60 80 100 120 140
Breast Cancer Disparities in U.S.A. Outcome disadvantages for African American breast cancer patients are observed for all tumor subtypes, and at all stages of disease
IV,>64 100% 80% 60% 40% 20% 0% 100% 80% 60% 40% 20% 0% Chu et al, SEER Data (Cancer, 2003) 6-Year Survival, ER-positive WA AA 6-Year Survival, ER-negative WA AA III,50-64 III,<50 II,>64 II,50-64 II,<50 I,>64 I, 50-64 IV,50-64 IV,<50 III,>64 I,<50
ETHNICITY AND EARLY-STAGE BREAST CANCER SEER Registry, 1990-94 T1 tumors: 1,860 AA and 27,429 WA AA WA ER neg 33.4% 18.4% Node pos 28.8% 21.3% Multivariate mortality hazard ratio for AA pts: 1.29 (1.18-1.41) Subset analysis of pts with 1 cm tumors Node pos: 17.4% AA vs. 11.7% WA (p<0.0001) Mortality hazard ratio for AA pts 1.15 (0.95-1.39) Blake et al, ASCO 2003
Distribution Group Comedo Status BREAST CANCER DISPARITIES ASCO, 2005 DCIS Outcome, SEER Data Age (5-yr groups) Race Lumpectomy Lumpectomy+RT Non-African American African American Absent 1.0 0.43 p<0.0001 0.93 p=0.003 1.70 Ipsilateral Breast Cancer Recurrence Hazard Ratio 1.0 p=0.0004 1.0 Present 1.25 p=0.06 Proportional Hazards Model; Baxter et al ASCO, 2005
BREAST CANCER IN YOUNG WOMEN: DETROIT SEER DATA, 1990-1999 507 AA and 1,378 W breast cancer pts <40 yrs Feature African American Caucasian P local 42.4% 52.1% Stage regional 45.7% 41.1% 0.001 distant 7.8% 4.4% Medullary Histology 5.8% 3.3% 0.021 ER Negative 61.9% 44.4% 0.001 PR Negative 59.7% 48.8% 0.001 Newman et al, CANCER, 2002
BREAST CANCER IN YOUNG WOMEN: DETROIT SEER DATA, 1990-1999 Proportional Hazard of Death*, AA compared to W pts Stage Local Regional Distant Risk Ratio 1.94 1.58 2.32 95% Confidence Interval 1.23-3.05 1.18-2.11 1.15-4.69 *adjusted for age, tumor size, nodal status, ER/PR & histology
Breast Cancer Disparities in U.S.A. Survival disadvantages for African American breast cancer patients are observed for all tumor subtypes, and at all stages of disease: Impact of global influences such as disparities in healthcare access and delivery of care
SES-Adjusted Meta-Analysis, 2006 >13K AA & 75K WA Breast CA Pts; 19 Studies Bassett Coates Gordon Ansell Neale Eley Perkins Simon (>49 yo) Simon (<50 yo) Franzini Howard Wojcik Yood El Tamer Roetzheim Albain Premen Albain Postmen Polednak Bradley Jatoi 1995-99 Crowe Combined.1.5 1 5 10 mortality hazard AA Mortality Risk: 1.28 (95% CI 1.18-1.38) 1.38) Newman et al JCO 2006
ETIOLOGY OF DISPARITIES IN BREAST CANCER OUTCOME Socioeconomic Resources Delivery of Care Tumor biology Genetics Lifestyle & Reproductive Experiences Environmental exposures Diet/Nutrition
Breast Cancer Disparities in U.S.A. Increased risk for early onset disease and development of aggressive breast cancer subtypes is observed in women with African ancestry across many variables
BREAST CANCER AGE DISTRIBUTION AND RACE-ETHNICITY Among U.S. women younger than 45 yrs, breast cancer incidence higher for AA population Median age at diagnosis 62 years for WA women 57 years for AA women 1/5 of WA pts are younger than 50 years 1/3 of AA breast pts are younger than 50 years
Breast Cancer Incidence by ER Status From Anderson et al, Breast Cancer Res and Treat, 2002
Disparities in Breast Tumor Biology: ER-Negative Breast Cancer in the U.S. Proportion ER-Negative Breast Cancer 45% 40% 35% 30% 25% 20% 15% 10% 5% 22% 39% 32% 25% 31% 0% White American African American American Indian Asian/Pacific Islander Hispanic/Latina American Li et al; SEER Data, 1992-98 Arch Int Med 2003
National Cancer Data Base: Frequency of ER-Neg Tumors by Age, Stage, and Income African American White American Age Category (years) 45 46-60 61-80 52% 41% 29% 35% 26% 17% Stage I 31% 17% II 42% 26% III 47% 32% IV 46% 30% Income <$30,000 37% 23% $30-$45,000 39% 23% $46,000 39% 21%
Microarray and Immunohistochemistry to Identify of Breast Tumor Subtypes Carolina Breast Cancer Study: Frequency of triple-negatives by IHC 50% 40% 30% 20% 10% 0% 39% 26% 16% 16% 14% 16% AA All WA All AA Premen WA Postmen AA Postmen WA Postmen Copyright restrictions may apply. Carey, L. A. et al. JAMA 2006;295:2492-2502.
ETIOLOGY OF DISPARITIES: HEREDITARY FACTORS? Common features of breast cancer among populations with African ancestry younger age distribution increased prevalence of medullary tumors increased prevalence of ER-neg, aneuploid tumors Increased incidence of male breast cancer
Breast Cancer in African American, Sub-Saharan African, and White American Women African 45 57 62 5:1 African American 2:1 3:1 White American Average Age at Diagnosis (years) Incidence:Mortality Ratio 80% 60% 4% 3% 40% 2% 20% 0% Proportion with Stage III/IV Proportion with High- Grade Tumors Proportion with ER- Negative Tumors 1% 0% Male Breast Cancer
Summary Globally, women with African ancestry represent a population that faces a decreased lifetime risk of estrogen receptorpositive breast cancer, and an increased risk for estrogen receptor-negative disease compared to other populations of women Do ethnicity/race-related variations in the oncogenic potential of mammary tissue exist? Exploration of this question requires improved metrics for correlating risk of disease with racial/ethnic ancestry