NAACCR 2018 Annual Conference Breast Cancer Subtypes Defined by HR/HER2 among Black Cases in the US by Birthplace Hyuna Sung, PhD; Carol Desantis, MPH; Stacey Fedawa, PhD; Ahmedin Jemal, DVM, PhD Surveillance & Health Services Research American Cancer Society 1
Breast Cancer Subtype by Race/Ethnicity HR-/HER2- (Tri-negative) Non-Hispanic Black: 27.2 per 100,000 (24%) Non-Hispanic White: 14.4 per 100,000 (12%) NHB 17 SEER Registries, 2010 Howlader N et al., J Natl Cancer Inst. 2014 2
Black and Black Immigrants Black and African Americans refers to a person having origins in any of the Black racial groups of Africa 1 Include peoples from different national, linguistic, ethnic, racial, cultural, social, and genetic backgrounds Black (40.9 M, 13%); non-hispanic White (61%); Hispanic or Latino (18%) (2016) 2 Black immigrants (foreign-born) About 10% of all black population (2016) 2 50% from Caribbean Islands; 36% from Africa 3 African immigrants are one of the fastest growing populations (2013) 3 1"The Black Population: 2010" (PDF), Census.gov, Sep 2011 2https://www.census.gov/quickfacts/fact/table/US#viewtop 3 3http://www.pewresearch.org/fact-tank/2018/01/24/key-facts-about-black-immigrants-in-the-u-s/
Triple-negative Breast Cancer (TNBC) in African vs. non-african cases Frequencies of TNBC (%) West African Central African East African Southern African US Black US White Newman LA, Kaljee LM. JAMA Surg. 2017 4
Prevalence Rate Ratio for ER- vs ER+: Foreign-born vs. US-born (ref.) Place of birth PRR (95% CI) PRR (95% CI) US-born black 1 (Reference) 1.5 (1.47 1.53) Jamaica-born black 0.88 (0.74 1.03) 1.31 (1.12 1.54) West Africa-born black 0.87 (0.70 1.08) 1.26 (1.03 1.55) East Africa-born black 0.58 (0.44 0.75) 0.85 (0.65 1.09) US-born white - 1 (Reference) SEER13 (1996-2008). Adjusted for age, diagnosis year, histology, and income Is the prevalence of ER-negative breast cancer in the US higher among Africa-born 5 than US-born black women? Jemal A, Fedewa SA. Breast Cancer Res Treat. 2012
Objectives Address heterogeneity in breast cancer subtype among black cases in the US Compare proportion in subtype defined by HR/HER2 status by birthplace Contrast the results to those in white breast cancer cases 6
Methods Data source: NAACCR Incidence Data - CiNA Analytic File, 1995-2014, for NHIAv2 Origin, Standard File, DeSantis - Breast cancer subtype in U.S. by POB, submitted Dec 2016. Registries: 47 states, Puerto Rico, and DC (96%) Years: 2010-2014 Participants: Non-Hispanic black and white invasive breast cancer cases with birthplace and breast tumor subtype 7
Black Breast Cancer Cases by Birthplace-country (NAACCR Item #254) US-born (37%) N=46,910 Foreignborn (5%) Birth country missing (59%) N=74,698 Non-Hispanic Blacks, Invasive breast cancer cases, NAACCR 2010-2014 8
Black Cases with Known Birthplace US-born n=46,910 (82%) Other places n=1,390 Caribbean N=3,280 (6.7%) West Africa n=597 (1.0%) East Africa N=348 (0.6%) Other Africa n=161 Non-Hispanic Blacks, Invasive breast cancer cases, NAACCR 2010-2014 9
Missing % in ER, PR, HER2 Status among Black Cases ER: Avg. 8.2% (range, 2.6% ~ 8.3%) PR: Avg. 8.4% (range, 3.2% ~ 8.5%) HER2: Avg. 15.6% (range, 8.3% ~ 15.7%) HR/HER2: Avg.15.9% (range, 8.3% ~ 16.9%) 10
Statistical Method Prevalence rate ratio (PRR) using log-binomial model HR (%)Forien born black PRR = HR + (%)Forien born black HR (%)US born black HR + (%)US born black HR- (ER- and PR-) / HR+ (ER+ or PR+) TN (ER-, PR-, and HER2-) / non-tn (ER+, PR+, or HER+) Adjustment for year of diagnosis, age, stage, grade, poverty rates, and missing status Comparison group vs. reference group Foreign-born black by birth place vs. US-born black Black by birth place vs. US-born white 11
Results 12
Selected Characteristics by Birthplace among Black Cases West East Birthplace US Caribbean Africa Africa n=46,910 n=3,280 n=597 n=348 Age at diagnosis <40 6% 8% 15% 15% 40-49 16% 20% 29% 31% 50-59 26% 29% 31% 29% 60-69 25% 23% 18% 19% 70+ 26% 21% 7% 6% Census tract poverty indicator Poverty <10% (high SES) 10% 17% 34% 29% Poverty 10-19.9% (med SES) 63% 51% 53% 63% Poverty 20% (low SES) 27% 32% 13% 7% AJCC 7th stage I 37% 35% 31% 31% II 34% 34% 33% 39% III 16% 19% 23% 19% IV 12% 12% 14% 12% Grade Well differentiated 14% 11% 10% 15% Moderately differentiated 37% 38% 32% 42% 13
HR/HER2 Status by Birthplace among Black Cases HR+/HER2- HR-/HER2+ HR+/HER2+ Tri-negative 100% 75% 50% 11% 26% 22% 24% 6% 8% 6% 14% 9% 14% 11% 14% Avr. HR+ 70% among black 25% 51% 56% 59% 69% 0% West Africa Caribbean US East Africa n=514 n=2,725 n=39,459 n=319 14
Foreign-born Black vs. US-born Black HR- vs. HR+ TN vs. non-tn US-born (ref.) Caribbean 0.95 (0.90-1.00) 0.89 (0.83-0.95) West Africa 1.05 (0.95-1.17) 0.98 (0.85-1.12) East Africa 0.62 (0.49-0.78) 0.48 (0.36-0.66) Prevalence rate ratio (95% CI) Adjusted for year of diagnosis, age, histology, AJCC 7th stage, grade, and poverty level. 15
HR/HER2 Status by Birthplace among Black and White Avr. HR+ 70% among black 100% 75% 50% HR+/HER2- HR-/HER2+ HR+/HER2+ Tri-negative 11% 11% 26% 22% 24% 6% 4% 10% 8% 6% 14% 9% 14% 11% 14% 25% 51% 56% 59% 69% 74% 0% West Africa Caribbean US-born East East Africa US-born US-born white black black black black white n=514 n=2,725 n=39,459 n=319 n=267,763 16
Black by Birthplace vs. White (ref.) HR- vs. HR+ TN vs. non-tn US-born white (ref.) US-born black 1.31 (1.29-1.33) 1.46 (1.43-1.49) Caribbean-born black West Africa-born black East Africa-born black 1.24 (1.18-1.30) 1.34 (1.21-1.48) 0.81 (0.65-1.02) 1.29 (1.21-1.38) 1.40 (1.23-1.60) 0.71 (0.53-0.96) Prevalence rate ratio (95% CI) Adjusted for year of diagnosis, age, histology, AJCC 7th stage, grade, and poverty level. 17
Volume & Direction of the Trans-Atlantic Slave Trade from Africa to Americas The Trans-Atlantic Slave Trade Database http://www.slavevoyages.org/ 18
Ancient Ethiopian Genome Reveals Extensive Eurasian Admixture in Eastern Africa Mota, 4500 years ago A migration into East Africa from Western Eurasia The Western Eurasian backflow mostly affected East Africa Llorente et al., Science. 192016
Summary of Findings Marked heterogeneity among black breast cancer cases by birthplace (East African-born vs. blacks) HR- tumor: East Africa-born, 38% low (vs. US-born black) TNBC East Africa-born, 52% low (vs. US-born black), 29% low (vs. US-born white) Caribbean Africa-born: 11% lower (vs. US-born black) Similar frequencies patterns, <50 and 50 years 20
Strengths and Limitations Nationally representative, high-quality population-based cancer registry data Higher missing rates in birth country variable Small sample size particularly Eastern-Africanborn black Potential misclassifications in subtype and birthplace Frequencies vs. Rates 21
Conclusions and Implications Marked heterogeneity among black breast cancer cases by birthplace Consistent to population migration history and supported by findings from population genetics The aggregate black category may not be always reflective of the characteristics of the entire black breast cancer cases Studies on breast cancer among black women may consider tumor heterogeneity within black populations Studies with ancestry informative markers and highquality cancer registry data in sub-saharan Africa can substantiate our finding 22
Acknowledgement North American Association of Central Cancer Registries American Cancer Society Carol Desantis, MPH Stacey Fedawa, PhD Ahmedin Jemal, DVM, PhD 23
Race 1,2,3,4,5 All resources in the facility, including the medical record, face sheet, physician and nursing notes, photographs, and any other sources, must be used to determine race. If a facility does not print race in the medical record but does maintain it in electronic form, the electronic data must also be reviewed. 24
Missing birth place % by diagnosis year 2010 : 59.0% 2011 : 59.1% 2012 : 59.5% 2013 : 56.6% 2014 : 56.7% 25
Black, known place of birth Black, unknown place of birth n=52,686 n=74,698 n % n % Year of diagnosis 2010 9494 18.6 14263 19.1 2011 9811 19.2 14824 19.8 2012 9880 19.3 15139 20.3 2013 10942 21.4 15114 20.2 2014 11008 21.5 15434 20.6 Age at diagnosis 20-49 11923 23.3 18532 24.8 50+ 39212 76.7 56242 75.2 Census track poverty indicator High SES, poverty <10% 5758 11.3 7877 10.5 Medium SES, poverty 10-19.9% 31661 62.0 44620 59.7 Low SES, poverty 20% 13681 26.8 22236 29.8 Unknown 35 41 Histology Ductal 39755 77.8 59374 79.4 Lobular 3616 7.1 5631 7.5 Others 7764 15.2 9769 13.1 AJCC 7th stage I 16649 36.9 27795 43.5 II 15471 34.3 23417 36.7 III 7483 16.6 8530 13.4 IV 5483 12.2 4137 6.5 Unknown 6049 10894 Grade Well differentiated 6052 13.6 10329 15.4 Moderately differentiated 16412 36.8 25737 38.4 Poorly or undifferentiated 22173 49.7 30926 46.2 Unknown 6498 7782 Molecular subtype HR+/HER2-25373 59.0 39771 61.8 HR+/HER2+ 4862 11.3 7240 11.2 HER2-enriched 2579 6.0 3542 5.5 Triple-negative 10203 23.7 13848 21.5 26
Selected Characteristics by Birthplace among Black and White Cases US-born black Caribbeanborn black West A- born black East A- born black US-born white n=46,910 n=3,280 n=597 n=348 n=316,438 Age at diagnosis <40 6% 8% 15% 15% 3% 40-49 16% 20% 29% 31% 12% 50-59 26% 29% 31% 29% 21% 60-69 25% 23% 18% 19% 27% 70+ 26% 21% 7% 6% 37% Census tract poverty indicator Poverty <10% (high SES) 10% 17% 34% 29% 19% Poverty 10-19.9% (med 63% 51% 53% 63% 70% SES) Poverty 20% (low SES) 27% 32% 13% 7% 11% AJCC 7th stage I 37% 35% 31% 31% 52% II 34% 34% 33% 39% 30% III 16% 19% 23% 19% 11% IV 12% 12% 14% 12% 8% Grade Well differentiated 14% 11% 10% 15% 23% Moderately differentiated 37% 38% 32% 42% 45% 27
Age < 50 years Age 50 years HR+/HER2- HR+/HER2+ HER2-enriched Tri-Negative HR+/HER2- HR+/HER2+ HER2-enriched Tri-Negative 0% 5% 0% 30% 8% 12% 23% 7% 16% 28% 7% 14% 10% 4% 18% 15% 5% 15% 100% 75% 50% 11% 11% 22% 21% 23% 8% 4% 9% 10% 8% 5% 10% 13% 10% 15% 5% 49% 54% 51% 68% 65% 25% 52% 57% 62% 71% 76% 0% West Africa-born black US-born black US-born white 0% West Africa-born black US-born black US-born white 28
Prevalence Rate Ratio: HR- vs. HR+ Total (n) HR- (%) PRR (95% CI) PRR (95% CI) adj US-born (ref) 43,020 29.3 1(ref) 1 (ref) Caribbean-born 3,038 28.7 0.99 (0.93 to 1.05) 0.95 (0.90-1.00) Western Africa-born 555 33.5 1.18 (1.05 to 1.33) 1.05 (0.95-1.17) Eastern Africa-born 338 17.2 0.57 (0.45 to 0.73) 0.62 (0.49-0.78) US-born white (ref) 292,301 15.7 1 (ref) 1 (ref) US-born black 43,020 29.3 1.90 (1.87 to 1.93) 1.31 (1.29-1.33) Caribbean-born black 3,038 28.7 1.88 (1.77 to 1.99) 1.24 (1.18-1.30) Western Africa-born 2.25 (2.00 to 555 33.5 black 2.53) 1.34 (1.21-1.48) Eastern Africa-born Adjustment: year of diagnosis, 338age at 17.2 diagnosis, 1.08 poverty (0.85 to level, 1.38) histology, 0.81 (0.65-1.02) AJCC black 7th stage, and grade. 29
Prevalence Rate Ratio: TN vs. non-tn Total (n) TN (%) PRR (95% CI) PRR (95% CI) adj US-born (ref) 39,459 23.9 1 (ref) 1 (ref) Caribbean-born 2,725 21.9 0.91 (0.85 to 0.98) 0.89 (0.83-0.95) Western Africa-born 514 25.9 1.08 (0.93 to 1.25) 0.98 (0.85-1.12) Eastern Africa-born 319 10.7 0.45 (0.32 to 0.61) 0.48 (0.36-0.66) US-born white (ref) 267,764 11.5 1 (ref) 1 (ref) US-born black 39,459 23.9 2.09 (2.04 to 2.13) 1.46 (1.43-1.49) Caribbean-born black 2,725 21.9 1.91 (1.78 to 2.05) 1.29 (1.21-1.38) Western Africa-born 2.26 (1.95 to 514 25.9 1.40 (1.23-1.60) black 2.61) Adjustment: Eastern Africa-born year of diagnosis, age at diagnosis, poverty level, histology, AJCC 7th 319 10.7 0.93 (0.68 to 1.28) 0.71 (0.53-0.96) black stage, and grade. 30
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African Ancestry & HR- Tumor Palmer JR et al., Genetic susceptibility loci for subtypes of breast cancer in an African American population. Cancer Epidemiol Biomarkers Prev. 2013 Jan 32
Indigenous Populations in Africa: ER+ vs. ER- Sub-region Number of Studies ER+, Proportion (95% CI) Study Heterogeneity, I 2 (P) North-East 0.63 (0.60-0.66) 85% (<0.001) North-West 0.59 (0.56-0.62) 91% (<0.001) South 6 0.60 (0.56-0.64) 52% (0.06) East 7 0.41 (0.33-0.50) 85% (<0.001) West 13 0.42 (0.34-0.50) 97% (<0.001) Eng A et al., Receptor-defined subtypes of breast cancer in indigenous populations in Africa: a systematic review and meta-analysis. PLoS medicine. 2014 33
Genetic Diversity among African Americans >70% African Ancestry (West) <25% European Ancestry <3% Native American Ancestry Southwest US Adhikari et la., Annu Rev Genomics Hum Genet, 2017 34
Eastern/Saharan Africa vs. Western/Central/Southern Africa PC1 (10.8% of the extracted variation) distinguishes eastern and Saharan Africa from western, central, and southern Africa Principal components analysis (n=2432 from 113 diverse populations) Tishkoff et al., Science 2009 35 May
http://www.pewresearch.org/fact-tank/2017/02/14/african-immigrant-population-in-u-s-steadily-climbs/ 36