Journal Article
. 2016 Dec; 161(3):491-499.
doi: 10.1007/s10549-016-4062-y.

Differences in the mutational landscape of triple-negative breast cancer in African Americans and Caucasians

Foluso O Ademuyiwa 1 Yu Tao 2 Jingqin Luo 2 Katherine Weilbaecher 3 Cynthia X Ma 3 
Affiliations
  • PMID: 27915434
  •     35 References
  •     30 citations

Abstract

Background: Triple-negative breast cancer (TNBC) occurs at higher frequency in African Americans compared with Caucasians. It is unclear if the biology of TNBC is different in African American versus Caucasians. In this study, we sought to evaluate racial differences in the molecular pathology of TNBC.

Methods: Using data from The Cancer Genome Atlas, we identified TNBC patients with information on race. We analyzed differences in clinical characteristics, tumor somatic mutations, and gene expression patterns by race from whole exome and microarray data.

Results: 1104 patients were identified, of which 178 had TNBC. TNBC was more frequent in African Americans than Caucasians (33.3 vs 14.9%). Although more African Americans than Caucasians overall were classified as basal-like from PAM50 gene expression (34.8 vs 16.1%), no differences in the TNBC cohort were observed. Median tumor somatic mutation counts were higher in African Americans versus Caucasians (39.5 vs 34), but no racial differences in the mutation counts in TNBC were observed. Somatic mutation analysis revealed racial differences in specific high prevalence genes in all patients (TP53 46% in African Americans vs 27% in Caucasians; PIK3CA 23% in African Americans vs 34% in Caucasians; and MLL3 12% in African Americans vs 6% in Caucasians). TNBC patients did not have any specific high prevalence genes associated with racial differences. There were no racial differences in gene expression patterns in selected genes involved in breast cancer biology. Overall, African Americans had shorter TTP and worse DFS. Racial differences in clinical outcomes were not observed in TNBC.

Conclusion: The mutational landscape of TNBC is similar between African Americans and Caucasians. The higher frequency of TNBC in African Americans is therefore not associated with a different genomic profile of commonly established tumor regulatory pathway genes. Other modifiable factors may exist that contribute to the racial disparity in TNBC.

Keywords: Genomics; Survival; Triple negative breast cancer.

Predictors of reduced dose intensity in patients with early-stage breast cancer receiving adjuvant chemotherapy.
Michelle Shayne, Jeffrey Crawford, +3 authors, ANC Study Group.
Breast Cancer Res Treat, 2006 May 18; 100(3). PMID: 16705366
Racial and Ethnic Differences in Breast Cancer Survival: Mediating Effect of Tumor Characteristics and Sociodemographic and Treatment Factors.
Erica T Warner, Rulla M Tamimi, +9 authors, Ann H Partridge.
J Clin Oncol, 2015 May 13; 33(20). PMID: 25964252    Free PMC article.
Highly Cited.
Identification of differentially expressed genes in breast tumors from African American compared with Caucasian women.
Lori A Field, Brad Love, +3 authors, Rachel E Ellsworth.
Cancer, 2011 Jul 30; 118(5). PMID: 21800289
Mortality risk of black women and white women with invasive breast cancer by hormone receptors, HER2, and p53 status.
Huiyan Ma, Yani Lu, +11 authors, Leslie Bernstein.
BMC Cancer, 2013 May 07; 13. PMID: 23642215    Free PMC article.
Differences in prevalence of obesity among black, white, and Hispanic adults - United States, 2006-2008.
Centers for Disease Control and Prevention (CDC).
MMWR Morb Mortal Wkly Rep, 2009 Jul 18; 58(27). PMID: 19609247
Highly Cited.
Breast cancer intratumor genetic heterogeneity: causes and implications.
Charlotte K Y Ng, Helen N Pemberton, Jorge S Reis-Filho.
Expert Rev Anticancer Ther, 2012 Oct 04; 12(8). PMID: 23030222
Review.
Physical activity from menarche to first pregnancy and risk of breast cancer.
Ying Liu, Deirdre K Tobias, +6 authors, Graham A Colditz.
Int J Cancer, 2016 May 01; 139(6). PMID: 27130486    Free PMC article.
Polymorphisms in the DNA repair gene XRCC1 and breast cancer.
E J Duell, R C Millikan, +7 authors, D A Bell.
Cancer Epidemiol Biomarkers Prev, 2001 Apr 17; 10(3). PMID: 11303590
Body-mass index and mortality risk in U.S. blacks compared to whites.
Chandra L Jackson, Nae-Yuh Wang, +3 authors, Frederick L Brancati.
Obesity (Silver Spring), 2013 Apr 05; 22(3). PMID: 23554375    Free PMC article.
Race and hormone receptor-positive breast cancer outcomes in a randomized chemotherapy trial.
Joseph A Sparano, Molin Wang, +9 authors, Nancy E Davidson.
J Natl Cancer Inst, 2012 Jan 18; 104(5). PMID: 22250182    Free PMC article.
Undertreatment of obese women receiving breast cancer chemotherapy.
Jennifer J Griggs, Melony E S Sorbero, Gary H Lyman.
Arch Intern Med, 2005 Jun 16; 165(11). PMID: 15956006
Ethnicity and breast cancer: factors influencing differences in incidence and outcome.
Rowan T Chlebowski, Zhao Chen, +9 authors, Ross Prentice.
J Natl Cancer Inst, 2005 Mar 17; 97(6). PMID: 15770008
Highly Cited.
Intrinsic breast tumor subtypes, race, and long-term survival in the Carolina Breast Cancer Study.
Katie M O'Brien, Stephen R Cole, +6 authors, Robert C Millikan.
Clin Cancer Res, 2010 Dec 21; 16(24). PMID: 21169259    Free PMC article.
Highly Cited.
A progression puzzle.
René Bernards, Robert A Weinberg.
Nature, 2002 Aug 23; 418(6900). PMID: 12192390
Highly Cited.
Triple receptor-negative breast cancer: the effect of race on response to primary systemic treatment and survival outcomes.
Shaheenah Dawood, Kristine Broglio, +9 authors, Ana Maria Gonzalez-Angulo.
J Clin Oncol, 2008 Dec 03; 27(2). PMID: 19047281    Free PMC article.
Differential expression of breast cancer-associated genes between stage- and age-matched tumor specimens from African- and Caucasian-American Women diagnosed with breast cancer.
Jessica M Grunda, Adam D Steg, +4 authors, William E Grizzle.
BMC Res Notes, 2012 May 24; 5. PMID: 22616718    Free PMC article.
Incidence and predictors of low dose-intensity in adjuvant breast cancer chemotherapy: a nationwide study of community practices.
Gary H Lyman, David C Dale, Jeffrey Crawford.
J Clin Oncol, 2003 Dec 16; 21(24). PMID: 14673039
Highly Cited.
Racial disparity in estrogen receptor positive breast cancer patients receiving trimodality therapy.
J L Wright, I M Reis, +7 authors, J Hurley.
Breast, 2011 Dec 20; 21(3). PMID: 22178596
Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression.
P Kuehl, J Zhang, +16 authors, E Schuetz.
Nat Genet, 2001 Mar 30; 27(4). PMID: 11279519
Highly Cited.
Hormone receptor status of breast tumors in black, Hispanic, and non-Hispanic white women. An analysis of 13,239 cases.
S M Gapstur, J Dupuis, +2 authors, D P Winchester.
Cancer, 1996 Apr 15; 77(8). PMID: 8608530
Histological characteristics of breast carcinoma in blacks and whites.
V W Chen, P Correa, +7 authors, M Sobhan.
Cancer Epidemiol Biomarkers Prev, 1994 Mar 01; 3(2). PMID: 7519506
A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer.
Soonmyung Paik, Steven Shak, +12 authors, Norman Wolmark.
N Engl J Med, 2004 Dec 14; 351(27). PMID: 15591335
Highly Cited.
Black race as a prognostic factor in triple-negative breast cancer patients treated with breast-conserving therapy: a large, single-institution retrospective analysis.
Carmen A Perez, Zachary S Zumsteg, +9 authors, Alice Y Ho.
Breast Cancer Res Treat, 2013 May 07; 139(2). PMID: 23645006
Breast Cancer Mortality in African-American and Non-Hispanic White Women by Molecular Subtype and Stage at Diagnosis: A Population-Based Study.
Li Tao, Scarlett Lin Gomez, +2 authors, Christina A Clarke.
Cancer Epidemiol Biomarkers Prev, 2015 May 15; 24(7). PMID: 25969506    Free PMC article.
Racial differences in outcomes of triple-negative breast cancer.
Jose M Pacheco, Feng Gao, +2 authors, Cynthia X Ma.
Breast Cancer Res Treat, 2013 Feb 13; 138(1). PMID: 23400579    Free PMC article.
Comprehensive molecular portraits of human breast tumours.
Cancer Genome Atlas Network.
Nature, 2012 Sep 25; 490(7418). PMID: 23000897    Free PMC article.
Highly Cited.
Race and breast cancer survival by intrinsic subtype based on PAM50 gene expression.
Candyce H Kroenke, Carol Sweeney, +8 authors, Bette J Caan.
Breast Cancer Res Treat, 2014 Mar 08; 144(3). PMID: 24604094    Free PMC article.
Epidemiology of basal-like breast cancer.
Robert C Millikan, Beth Newman, +13 authors, Charles M Perou.
Breast Cancer Res Treat, 2007 Jun 21; 109(1). PMID: 17578664    Free PMC article.
Highly Cited.
Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry.
Katrina R Bauer, Monica Brown, +2 authors, Vincent Caggiano.
Cancer, 2007 Mar 28; 109(9). PMID: 17387718
Highly Cited.
Race and triple negative threats to breast cancer survival: a population-based study in Atlanta, GA.
Mary Jo Lund, Katrina F Trivers, +7 authors, J William Eley.
Breast Cancer Res Treat, 2008 Mar 08; 113(2). PMID: 18324472
Highly Cited.
Trends in breast cancer by race and ethnicity: update 2006.
Carol Smigal, Ahmedin Jemal, +4 authors, Michael Thun.
CA Cancer J Clin, 2006 Jun 02; 56(3). PMID: 16737949
Highly Cited.
Does race affect outcomes in triple negative breast cancer?
Jasgit C Sachdev, Saira Ahmed, +3 authors, Mohammad Jahanzeb.
Breast Cancer (Auckl), 2010 Aug 11; 4. PMID: 20697530    Free PMC article.
Meta-analysis of survival in African American and white American patients with breast cancer: ethnicity compared with socioeconomic status.
Lisa A Newman, Kent A Griffith, +3 authors, Graham A Colditz.
J Clin Oncol, 2006 Mar 22; 24(9). PMID: 16549828
Highly Cited.
Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study.
Lisa A Carey, Charles M Perou, +14 authors, Robert C Millikan.
JAMA, 2006 Jun 08; 295(21). PMID: 16757721
Highly Cited.
Comparison of the Genomic Landscape Between Primary Breast Cancer in African American Versus White Women and the Association of Racial Differences With Tumor Recurrence.
Tanya Keenan, Beverly Moy, +6 authors, Aditya Bardia.
J Clin Oncol, 2015 Sep 16; 33(31). PMID: 26371147    Free PMC article.
Highly Cited.
Germline Mutations in Triple-Negative Breast Cancer.
Eric Hahnen, Jan Hauke, +3 authors, Rita K Schmutzler.
Breast Care (Basel), 2017 Jun 15; 12(1). PMID: 28611536    Free PMC article.
Review.
Immunohistochemistry defined subtypes of breast cancer in 678 Sudanese and Eritrean women; hospitals based case series.
Asmerom Tesfamariam Sengal, Nada Suliman Haj-Mukhtar, +3 authors, Ahmed A Mohamedani.
BMC Cancer, 2017 Dec 02; 17(1). PMID: 29191181    Free PMC article.
Race Disparities in the Contribution of miRNA Isoforms and tRNA-Derived Fragments to Triple-Negative Breast Cancer.
Aristeidis G Telonis, Isidore Rigoutsos.
Cancer Res, 2017 Dec 13; 78(5). PMID: 29229607    Free PMC article.
Breast cancer metastasis through the lympho-vascular system.
S David Nathanson, David Krag, +5 authors, Timothy P Padera.
Clin Exp Metastasis, 2018 May 26; 35(5-6). PMID: 29796854
Review.
Whole exome sequencing of breast cancer (TNBC) cases from India: association of MSH6 and BRIP1 variants with TNBC risk and oxidative DNA damage.
M Aravind Kumar, Shaik Mohammad Naushad, +4 authors, M Lakshmi Narasu.
Mol Biol Rep, 2018 Aug 24; 45(5). PMID: 30136158
Detection of PIK3/AKT pathway in Moroccan population with triple negative breast cancer.
Farah Jouali, Nabila Marchoudi, +4 authors, Jamal Fekkak.
BMC Cancer, 2018 Sep 20; 18(1). PMID: 30227836    Free PMC article.
JAK3 Variant, Immune Signatures, DNA Methylation, and Social Determinants Linked to Survival Racial Disparities in Head and Neck Cancer Patients.
Rafael Guerrero-Preston, Fahcina Lawson, +14 authors, David Sidransky.
Cancer Prev Res (Phila), 2019 Feb 20; 12(4). PMID: 30777857    Free PMC article.
Deconvolution of the Genomic and Epigenomic Interaction Landscape of Triple-Negative Breast Cancer.
Jiande Wu, Tarun Karthik Kumar Mamidi, Lu Zhang, Chindo Hicks.
Cancers (Basel), 2019 Nov 07; 11(11). PMID: 31683572    Free PMC article.
Pan-cancer clinical and molecular analysis of racial disparities.
Olivia D Lara, Ying Wang, +9 authors, Anil K Sood.
Cancer, 2019 Nov 16; 126(4). PMID: 31730714    Free PMC article.
Integrated Analysis of Genetic Ancestry and Genomic Alterations across Cancers.
Jiao Yuan, Zhongyi Hu, +22 authors, Lin Zhang.
Cancer Cell, 2018 Oct 10; 34(4). PMID: 30300578    Free PMC article.
Atypical Chemokine Receptor 1 (DARC/ACKR1) in Breast Tumors Is Associated with Survival, Circulating Chemokines, Tumor-Infiltrating Immune Cells, and African Ancestry.
Brittany D Jenkins, Rachel N Martini, +15 authors, Melissa B Davis.
Cancer Epidemiol Biomarkers Prev, 2019 Apr 05; 28(4). PMID: 30944146    Free PMC article.
Greater Survival Improvement in African American vs. Caucasian Women with Hormone Negative Breast Cancer.
Robert Wieder, Basit Shafiq, Nabil Adam.
J Cancer, 2020 Apr 01; 11(10). PMID: 32226499    Free PMC article.
Somatic mutations of triple-negative breast cancer: a comparison between Black and White women.
Angela R Omilian, Lei Wei, +5 authors, Song Yao.
Breast Cancer Res Treat, 2020 May 23; 182(2). PMID: 32441016    Free PMC article.
Breast and prostate cancers harbor common somatic copy number alterations that consistently differ by race and are associated with survival.
Yalei Chen, Sudha M Sadasivan, +11 authors, Albert M Levin.
BMC Med Genomics, 2020 Aug 21; 13(1). PMID: 32819446    Free PMC article.
Racial Disparity and Triple-Negative Breast Cancer in African-American Women: A Multifaceted Affair between Obesity, Biology, and Socioeconomic Determinants.
Sumit Siddharth, Dipali Sharma.
Cancers (Basel), 2018 Dec 19; 10(12). PMID: 30558195    Free PMC article.
Review.
Tumor mutational profile of triple negative breast cancer patients in Thailand revealed distinctive genetic alteration in chromatin remodeling gene.
Suvimol Niyomnaitham, Napa Parinyanitikul, +7 authors, Manop Pithukpakorn.
PeerJ, 2019 Mar 05; 7. PMID: 30828495    Free PMC article.
The distinct clinicopathological and prognostic implications of PIK3CA mutations in breast cancer patients from Central China.
Haibo Wu, Wei Wang, +8 authors, Wenchu Lin.
Cancer Manag Res, 2019 Mar 14; 11. PMID: 30863158    Free PMC article.
MAT2B expression correlates with poor prognosis in triple-negative breast cancer.
Jin Xu, Di Wu, Siliang Wang, Zhe Wang.
Cancer Manag Res, 2019 Jul 30; 11. PMID: 31354356    Free PMC article.
Patterns of Mutation Enrichment in Metastatic Triple-Negative Breast Cancer.
César H Saravia, Claudio Flores, +5 authors, Joseph A Pinto.
Clin Med Insights Oncol, 2019 Aug 27; 13. PMID: 31447598    Free PMC article.
Targeted sequencing reveals the somatic mutation landscape in a Swedish breast cancer cohort.
Argyri Mathioudaki, Viktor Ljungström, +9 authors, Kerstin Lindblad-Toh.
Sci Rep, 2020 Nov 11; 10(1). PMID: 33168853    Free PMC article.
Evaluating the therapeutic potential of ADAR1 inhibition for triple-negative breast cancer.
Che-Pei Kung, Kyle A Cottrell, +7 authors, Jason D Weber.
Oncogene, 2020 Oct 29; 40(1). PMID: 33110236    Free PMC article.
Racial Disparities in Triple Negative Breast Cancer: A Review of the Role of Biologic and Non-biologic Factors.
Om Prakash, Fokhrul Hossain, +3 authors, Lucio Miele.
Front Public Health, 2021 Jan 09; 8. PMID: 33415093    Free PMC article.
Review.
Ancestry-associated transcriptomic profiles of breast cancer in patients of African, Arab, and European ancestry.
Jessica Roelands, Raghvendra Mall, +11 authors, Julie Decock.
NPJ Breast Cancer, 2021 Feb 10; 7(1). PMID: 33558495    Free PMC article.
Poor Survival and Differential Impact of Genetic Features of Black Patients with Acute Myeloid Leukemia.
Bhavana Bhatnagar, Jessica Kohlschmidt, +20 authors, Ann-Kathrin Eisfeld.
Cancer Discov, 2020 Dec 06; 11(3). PMID: 33277314    Free PMC article.
Distinct Somatic Alteration Features Identified by Gene Panel Sequencing in Korean Triple-Negative Breast Cancer with High Ki67 Expression.
Woo Young Sun, Jina Lee, +2 authors, Joonhong Park.
Diagnostics (Basel), 2021 Apr 04; 11(3). PMID: 33804295    Free PMC article.
Mechanisms of breast cancer metastasis.
S David Nathanson, Michael Detmar, +6 authors, Kevin Cheung.
Clin Exp Metastasis, 2021 May 06;. PMID: 33950409
Review.
Spectrum of PIK3CA/AKT mutations across molecular subtypes of triple-negative breast cancer.
Sandeep Kumar, Amanjit Bal, +4 authors, Gurpreet Singh.
Breast Cancer Res Treat, 2021 May 07; 187(3). PMID: 33954864
Evaluation of Racial/Ethnic Differences in Treatment and Mortality Among Women With Triple-Negative Breast Cancer.
Beomyoung Cho, Yunan Han, +4 authors, Ying Liu.
JAMA Oncol, 2021 May 14; 7(7). PMID: 33983438    Free PMC article.
Reproductive factors and risk of breast cancer by tumor subtypes among Ghanaian women: A population-based case-control study.
Jonine D Figueroa, Brittny C Davis Lynn, +16 authors, Ghana Breast Health Study Team.
Int J Cancer, 2020 Feb 19; 147(6). PMID: 32068253    Free PMC article.
Differential mutation spectrum and immune landscape in African Americans versus Whites: A possible determinant to health disparity in head and neck cancer.
Sanjib Chaudhary, Vi Dam, +10 authors, Surinder K Batra.
Cancer Lett, 2020 Aug 02; 492. PMID: 32738272    Free PMC article.