Triple-Negative Breast Cancer, Stem Cells, and African Ancestry
2017; Elsevier BV; Volume: 188; Issue: 2 Linguagem: Inglês
10.1016/j.ajpath.2017.06.020
ISSN1525-2191
AutoresEvelyn Jiagge, Dhananjay Chitale, Lisa A. Newman,
Tópico(s)BRCA gene mutations in cancer
ResumoTriple-negative breast cancers (TNBCs) are more common among African-ancestry populations, such as African Americans and western, sub-Saharan Africans, compared with European-ancestry populations. This phenotype prevalence contributes to disparities in breast cancer outcomes between African Americans and White Americans. Breast cancer stem cells represent the tumor subpopulation involved in metastatic virulence, and ongoing research seeks to characterize the extent to which TNBC versus non-TNBC stem cells may differ. This review summarizes the existing literature regarding TNBCs and stem cells as they pertain to the burden of breast cancer among African-ancestry populations. Additional research related to variations in somatic tumor genomics between the African-American and White-American populations is also summarized. This review furthermore explores the history of insights regarding breast cancer disparities related to racial/ethnic identity, socioeconomic status, and tumor biology. Triple-negative breast cancers (TNBCs) are more common among African-ancestry populations, such as African Americans and western, sub-Saharan Africans, compared with European-ancestry populations. This phenotype prevalence contributes to disparities in breast cancer outcomes between African Americans and White Americans. Breast cancer stem cells represent the tumor subpopulation involved in metastatic virulence, and ongoing research seeks to characterize the extent to which TNBC versus non-TNBC stem cells may differ. This review summarizes the existing literature regarding TNBCs and stem cells as they pertain to the burden of breast cancer among African-ancestry populations. Additional research related to variations in somatic tumor genomics between the African-American and White-American populations is also summarized. This review furthermore explores the history of insights regarding breast cancer disparities related to racial/ethnic identity, socioeconomic status, and tumor biology. Triple-negative breast cancer (TNBC) is the term commonly used to describe cancers that are negative for the expression of estrogen and progesterone receptors and that lack overexpression of tyrosine kinase-type cell surface receptor HER2/Neu. Approximately 80% of TNBC tumors have the inherently aggressive basal breast cancer subtype as defined by gene-expression studies; the TNBC phenotype is therefore often used as a surrogate to identify patients with the biologically unfavorable basal subtype. The absence of expression of these three biomarkers also carries clinical relevance with regard to the mechanisms of currently available targeted therapies for breast cancer. An array of selective estrogen receptor modulators and aromatase inhibitors can be offered as endocrine therapy for patients with hormone receptor–positive breast cancer, and targeted anti-HER2 agents are effective in managing HER2/Neu-overexpressing breast cancers. Systemic therapy is especially important in addressing the virulent nature of most TNBC cases, but general, nontargeted chemotherapy remains the standard-of-care, routine approach. Recent data suggest that breast cancers are heterogeneous and that only a small and discrete subpopulation of cells within a tumor, called the breast cancer stem cells (BCSCs), possesses self-renewal capacity and the ability to establish metastatic colonies.1Charafe-Jauffret E. Ginestier C. Iovino F. Wicinski J. Cervera N. Finetti P. Hur M.H. Diebel M.E. Monville F. Dutcher J. Brown M. Viens P. Xerri L. Bertucci F. Stassi G. Dontu G. Birnbaum D. Wicha M.S. Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature.Cancer Res. 2009; 69: 1302-1313Crossref PubMed Scopus (943) Google Scholar, 2Dontu G. Abdallah W.M. Foley J.M. Jackson K.W. Clarke M.F. Kawamura M.J. Wicha M.S. In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells.Genes Dev. 2003; 17: 1253-1270Crossref PubMed Scopus (1982) Google Scholar Population-based breast cancer mortality rates are higher among women who self-identify as African American compared with White Americans (alias Caucasian Americans). The burden of breast cancer mortality is also elevated among African women residing on the continent of Africa. These two populations will be described as having African ancestry. TNBCs, BCSCs, and breast cancer patients of African ancestry represent three distinct topics that feature at least one common denominator: an association with increased breast cancer virulence. Each of these topics can be furthermore correlated with one another to varying degrees: i) TNBC is more common among women of western, sub-Saharan African ancestry3Kohler B.A. Sherman R.L. Howlader N. Jemal A. Ryerson A.B. Henry K.A. Boscoe F.P. Cronin K.A. Lake A. Noone A.M. Henley S.J. Eheman C.R. Anderson R.N. Penberthy L. Annual report to the nation on the status of cancer, 1975-2011, featuring incidence of breast cancer subtypes by race/ethnicity, poverty, and state.J Natl Cancer Inst. 2015; 107: djv048Crossref PubMed Scopus (553) Google Scholar, 4Newman L.A. Reis-Filho J.S. Morrow M. Carey L.A. King T.A. The 2014 Society of Surgical Oncology Susan G. Komen for the Cure Symposium: triple-negative breast cancer.Ann Surg Oncol. 2015; 22: 874-882Crossref PubMed Scopus (83) Google Scholar, 5Jiagge E. Jibril A.S. Chitale D. Bensenhaver J.M. Awuah B. Hoenerhoff M. Adjei E. Bekele M. Abebe E. Nathanson S.D. Gyan K. Salem B. Oppong J. Aitpillah F. Kyei I. Bonsu E.O. Proctor E. Merajver S.D. Wicha M. Stark A. Newman L.A. Comparative analysis of breast cancer phenotypes in African American, White American, and West versus East African patients: correlation between African ancestry and triple-negative breast cancer.Ann Surg Oncol. 2016; 23: 3843-3849Crossref PubMed Scopus (50) Google Scholar, 6Brewster A.M. Chavez-MacGregor M. Brown P. Epidemiology, biology, and treatment of triple-negative breast cancer in women of African ancestry.Lancet Oncol. 2014; 15: e625-e634Abstract Full Text Full Text PDF PubMed Scopus (159) Google Scholar; ii) TNBC/basal subtype tumors are enriched with populations of cells that express BCSC markers7Yang F. Cao L. Sun Z. Jin J. Fang H. Zhang W. Guan X. Evaluation of breast cancer stem cells and intratumor stemness heterogeneity in triple-negative breast cancer as prognostic factors.Int J Biol Sci. 2016; 12: 1568-1577Crossref PubMed Scopus (29) Google Scholar, 8Guler G. Balci S. Costinean S. Ussakli C. Irkkan C. Suren D. Sari E. Altundag K. Ozisik Y. Jones S. Bacher J. Shapiro C. Huebner K. Stem cell-related markers in primary breast cancers and associated metastatic lesions.Mod Pathol. 2012; 25: 949-955Crossref PubMed Scopus (32) Google Scholar, 9Olsson E. Honeth G. Bendahl P.O. Saal L.H. Gruvberger-Saal S. Ringner M. Vallon-Christersson J. Jonsson G. Holm K. Lovgren K. Ferno M. Grabau D. Borg A. Hegardt C. CD44 isoforms are heterogeneously expressed in breast cancer and correlate with tumor subtypes and cancer stem cell markers.BMC Cancer. 2011; 11: 418Crossref PubMed Scopus (155) Google Scholar, 10Honeth G. Bendahl P.O. Ringner M. Saal L.H. Gruvberger-Saal S.K. Lovgren K. Grabau D. Ferno M. Borg A. Hegardt C. The CD44+/CD24− phenotype is enriched in basal-like breast tumors.Breast Cancer Res. 2008; 10: R53Crossref PubMed Scopus (455) Google Scholar; and iii) breast cancer patients of western, sub-Saharan African ancestry have an increased prevalence of tumors that express stem cell markers.11Schwartz T. Stark A. Pang J. Awuah B. Kleer C.G. Quayson S. Kingman S. Aitpillah F. Abantanga F. Jiagge E. Oppong J.K. Osei-Bonsu E. Martin I. Yan X. Toy K. Adjei E. Wicha M. Newman L.A. Expression of aldehyde dehydrogenase 1 as a marker of mammary stem cells in benign and malignant breast lesions of Ghanaian women.Cancer. 2013; 119: 488-494Crossref PubMed Scopus (34) Google Scholar, 12Nalwoga H. Arnes J.B. Wabinga H. Akslen L.A. Expression of aldehyde dehydrogenase 1 (ALDH1) is associated with basal-like markers and features of aggressive tumours in African breast cancer.Br J Cancer. 2010; 102: 369-375Crossref PubMed Scopus (82) Google Scholar, 13Nakshatri H. Anjanappa M. Bhat-Nakshatri P. Ethnicity-dependent and -independent heterogeneity in healthy normal breast hierarchy impacts tumor characterization.Sci Rep. 2015; 5: 13526Crossref PubMed Scopus (32) Google Scholar, 14Pang J. Toy K.A. Griffith K.A. Awuah B. Quayson S. Newman L.A. Kleer C.G. Invasive breast carcinomas in Ghana: high frequency of high grade, basal-like histology and high EZH2 expression.Breast Cancer Res Treat. 2012; 135: 59-66Crossref PubMed Scopus (32) Google Scholar The extent to which the correlations described above represent evidence of genetic/hereditary variation in BCSCs associated with African ancestry versus representing the true, true and unrelated non sequitur remains uncertain. This review will summarize the published literature on TNBC, BCSCs, and their possible relationships with African ancestry. Our group has introduced the term oncologic anthropology as a transdisciplinary field of study that combines the expertise of social scientists, geneticists, and translational oncologists in an effort to address these complex issues.15Newman L.A. Kaljee L.M. Health disparities and triple-negative breast cancer in African American women: a review.JAMA Surg. 2017; 152: 485-493Crossref PubMed Scopus (161) Google Scholar Disparities in breast cancer outcomes related to racial/ethnic identity have been well documented for several decades, with the most prominent correlation being higher mortality rates among African-American compared with White-American women.16DeSantis C.E. Fedewa S.A. Goding Sauer A. Kramer J.L. Smith R.A. Jemal A. Breast cancer statistics, 2015: convergence of incidence rates between black and white women.CA Cancer J Clin. 2016; 66: 31-42Crossref PubMed Scopus (888) Google Scholar, 17Baquet C.R. Mishra S.I. Commiskey P. Ellison G.L. DeShields M. Breast cancer epidemiology in blacks and whites: disparities in incidence, mortality, survival rates and histology.J Natl Med Assoc. 2008; 100: 480-488Abstract Full Text PDF PubMed Google Scholar Poverty rates and inadequate health insurance coverage are also more common in the African-American compared with White-American communities, and these socioeconomic disadvantages likely contribute to the disparities in breast cancer outcomes by causing delays in diagnosis, more advanced stage distribution at diagnosis, and inadequate multidisciplinary breast cancer treatment.18Bigby J. Holmes M.D. Disparities across the breast cancer continuum.Cancer Causes Control. 2005; 16: 35-44Crossref PubMed Scopus (136) Google Scholar, 19Tannenbaum S.L. Koru-Sengul T. Miao F. Byrne M.M. Disparities in survival after female breast cancer diagnosis: a population-based study.Cancer Causes Control. 2013; 24: 1705-1715Crossref PubMed Scopus (38) Google Scholar, 20Tian N. Goovaerts P. Zhan F.B. Chow T.E. Wilson J.G. Identifying risk factors for disparities in breast cancer mortality among African-American and Hispanic women.Womens Health Issues. 2012; 22: e267-e276Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar The downstream effects of impaired health care access do not completely explain the disparities in breast cancer outcomes, as African Americans have worse survival rates even after controlling for stage at diagnosis.15Newman L.A. Kaljee L.M. Health disparities and triple-negative breast cancer in African American women: a review.JAMA Surg. 2017; 152: 485-493Crossref PubMed Scopus (161) Google Scholar, 21Deshpande A.D. Jeffe D.B. Gnerlich J. Iqbal A.Z. Thummalakunta A. Margenthaler J.A. Racial disparities in breast cancer survival: an analysis by age and stage.J Surg Res. 2009; 153: 105-113Google Scholar An evaluation of race/ethnicity-associated variations in primary tumor biology is therefore warranted, and the presence of such differences is supported by additional epidemiologic data regarding the burden of breast cancer in diverse population subsets. Historically, population-based incidence rates of breast cancer have been lower in African-American compared with White-American women, and fluctuations in incidence have typically occurred in parallel. Paradoxically, however, population-based breast cancer mortality rates were similar in both groups until the early 1980s, at which point the mortality curves separated as a consequence of declining mortality rates in White Americans contrasted against relatively stable mortality rates in African Americans. The mortality gap that emerged very likely reflected the unmasking of differences in the biology of breast cancer between African-American and White-American women related to the prevalence of biomarker expression and the development of targeted therapy for breast cancer. Tamoxifen became approved as systemic therapy for breast cancer in 1977, and this endocrine agent represents the first targeted therapy for breast cancer, improving outcomes in hormone receptor–positive disease. Tamoxifen-related reductions in population-based mortality rates became apparent by the early 1980s, but these benefits were predominantly experienced by the White-American patient population, because hormone receptor–positive breast cancer is twice as common among White Americans compared with African Americans.22Newman L.A. Parsing the etiology of breast cancer disparities.J Clin Oncol. 2016; 34: 1013-1014Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar Population-based breast cancer incidence rates have been rising disproportionately among African Americans in recent years, and these rates have now converged with those of White Americans.16DeSantis C.E. Fedewa S.A. Goding Sauer A. Kramer J.L. Smith R.A. Jemal A. Breast cancer statistics, 2015: convergence of incidence rates between black and white women.CA Cancer J Clin. 2016; 66: 31-42Crossref PubMed Scopus (888) Google Scholar Rising incidence of breast cancer coupled with the disproportionately high frequency of the biologically aggressive TNBC phenotype in African-American women have resulted in worsening of the breast cancer population–based mortality gap, and this disparity is now a difference of 42%.16DeSantis C.E. Fedewa S.A. Goding Sauer A. Kramer J.L. Smith R.A. Jemal A. Breast cancer statistics, 2015: convergence of incidence rates between black and white women.CA Cancer J Clin. 2016; 66: 31-42Crossref PubMed Scopus (888) Google Scholar A variety of epidemiologic and statistical research tools have been utilized in the effort to disentangle the effects of African-American identity from the potentially confounding influences of socioeconomic disadvantage on breast cancer risk and outcome. Two sequential meta-analyses published in 200223Newman L.A. Mason J. Cote D. Vin Y. Carolin K. Bouwman D. Colditz G.A. African-American ethnicity, socioeconomic status, and breast cancer survival: a meta-analysis of 14 studies involving over 10,000 African-American and 40,000 White American patients with carcinoma of the breast.Cancer. 2002; 94: 2844-2854Crossref PubMed Scopus (15) Google Scholar and 200624Newman L.A. Griffith K.A. Jatoi I. Simon M.S. Crowe J.P. Colditz G.A. Meta-analysis of survival in African American and white American patients with breast cancer: ethnicity compared with socioeconomic status.J Clin Oncol. 2006; 24: 1342-1349Crossref PubMed Scopus (159) Google Scholar pooled the data from publications on breast cancer survival that adjusted for socioeconomic status in African-American compared with White-American patients, with both demonstrating that African-American identity remained a statistically significant risk factor for adverse outcomes. The latter report featured data represented by >14,000 African-American and 76,000 White-American patients, revealing a statistically significant mortality hazard ratio of 1.27 (95% CI, 1.18–1.38).24Newman L.A. Griffith K.A. Jatoi I. Simon M.S. Crowe J.P. Colditz G.A. Meta-analysis of survival in African American and white American patients with breast cancer: ethnicity compared with socioeconomic status.J Clin Oncol. 2006; 24: 1342-1349Crossref PubMed Scopus (159) Google Scholar Another approach to evaluating breast cancer disparities related to racial/ethnic identity involves the evaluation of data from clinical trials. The bedrock principle of the cancer clinical trials mechanism is that highest-level evidence regarding optimal oncology care is provided through monitoring outcomes in patients receiving tightly regulated and standardized treatment regimens. Albain et al25Albain K.S. Unger J.M. Crowley J.J. Coltman Jr., C.A. Hershman D.L. Racial disparities in cancer survival among randomized clinical trials patients of the Southwest Oncology Group.J Natl Cancer Inst. 2009; 101: 984-992Crossref PubMed Scopus (272) Google Scholar attempted to address the question of whether equal treatment in the context of clinical trial participation resulted in equal outcomes (regardless of racial/ethnic identity) by evaluating data from prospective, randomized trials from the Southwest Oncology Group. This robust pooled analysis of data from nearly 20,000 cancer patients (approximately 12% African Americans) treated in 35 trials between 1974 and 2001 found that racial/ethnic identity did not affect outcomes in the majority of malignancies, but results differed in the hormonally driven, sex-specific cancers. Outcome disparities related to African-American identity were observed in breast, prostate, and ovarian cancers, but not in lung or colon cancer, or in lymphoma, leukemia, or myeloma. Ten-year overall survival in premenopausal African-American women with early-stage breast cancer was 68% compared with 77% in comparable patients with other racial/ethnic identities, and 52% versus 62%, respectively, in those with early-stage, postmenopausal breast cancer.25Albain K.S. Unger J.M. Crowley J.J. Coltman Jr., C.A. Hershman D.L. Racial disparities in cancer survival among randomized clinical trials patients of the Southwest Oncology Group.J Natl Cancer Inst. 2009; 101: 984-992Crossref PubMed Scopus (272) Google Scholar The Women's Health Initiative is a massive prospective study of postmenopausal women's health that includes data on the incidence of breast cancer among >150,000 participants. After a median follow-up of 6.3 years, nearly 4000 breast cancers were diagnosed, and among this entire cohort of carefully screened women, the African-American participants were nearly five times as likely as the White Americans to develop high-grade, receptor-negative breast cancers, and the group had a significantly higher mortality hazard ratio of 1.79 (95% CI, 1.05 to 3.05).26Chlebowski R.T. Chen Z. Anderson G.L. Rohan T. Aragaki A. Lane D. Dolan N.C. Paskett E.D. McTiernan A. Hubbell F.A. Adams-Campbell L.L. Prentice R. Ethnicity and breast cancer: factors influencing differences in incidence and outcome.J Natl Cancer Inst. 2005; 97: 439-448Crossref PubMed Scopus (356) Google Scholar The expression of the HER2/Neu biomarker was not included in this analysis. The approximately twofold increased risk for TNBC in African-American women has been confirmed by population-based incidence rates regionally27Amirikia K.C. Mills P. Bush J. Newman L.A. Higher population-based incidence rates of triple-negative breast cancer among young African-American women: implications for breast cancer screening recommendations.Cancer. 2011; 117: 2747-2753Crossref PubMed Scopus (470) Google Scholar as well as nationally,3Kohler B.A. Sherman R.L. Howlader N. Jemal A. Ryerson A.B. Henry K.A. Boscoe F.P. Cronin K.A. Lake A. Noone A.M. Henley S.J. Eheman C.R. Anderson R.N. Penberthy L. Annual report to the nation on the status of cancer, 1975-2011, featuring incidence of breast cancer subtypes by race/ethnicity, poverty, and state.J Natl Cancer Inst. 2015; 107: djv048Crossref PubMed Scopus (553) Google Scholar and across all age intervals. Compared with non-TNBC, triple-negative disease has been confirmed to be an adverse prognostic feature in African-American patients.28Akinyemiju T. Moore J.X. Altekruse S.F. Breast cancer survival in African-American women by hormone receptor subtypes.Breast Cancer Res Treat. 2015; 153: 211-218Crossref PubMed Scopus (163) Google Scholar It is also noteworthy that data from the Surveillance, Epidemiology, and End Results Program linked to the American Community Survey failed to demonstrate an association between TNBC and socioeconomic status.29Akinyemiju T.F. Pisu M. Waterbor J.W. Altekruse S.F. Socioeconomic status and incidence of breast cancer by hormone receptor subtype.Springerplus. 2015; 4: 508Crossref PubMed Scopus (16) Google Scholar International patterns of breast cancer biomarker expression have prompted additional hypothesis-generating observations regarding a possible hereditary link between African ancestry and the triple-negative phenotype. Population-based data on breast cancer burden in Africa are sparse, but several studies have revealed notably higher frequencies of estrogen receptor–negative disease and TNBC among African patients.6Brewster A.M. Chavez-MacGregor M. Brown P. Epidemiology, biology, and treatment of triple-negative breast cancer in women of African ancestry.Lancet Oncol. 2014; 15: e625-e634Abstract Full Text Full Text PDF PubMed Scopus (159) Google Scholar, 30Newman L.A. Disparities in breast cancer and African ancestry: a global perspective.Breast J. 2015; 21: 133-139Crossref PubMed Scopus (62) Google Scholar, 31Jiagge E. Bensenhaver J.M. Oppong J.K. Awuah B. Newman L.A. Global surgical oncology disease burden: addressing disparities via global surgery initiatives: the University of Michigan International Breast Cancer Registry.Ann Surg Oncol. 2015; 22: 734-740Crossref PubMed Scopus (48) Google Scholar The highest prevalence rates are observed in western, sub-Saharan Africa, where triple-negative disease has accounted for 27% to 61% of cases.32Huo D. Ikpatt F. Khramtsov A. Dangou J.M. Nanda R. Dignam J. Zhang B. Grushko T. Zhang C. Oluwasola O. Malaka D. Malami S. Odetunde A. Adeoye A.O. Iyare F. Falusi A. Perou C.M. Olopade O.I. Population differences in breast cancer: survey in indigenous African women reveals over-representation of triple-negative breast cancer.J Clin Oncol. 2009; 27: 4515-4521Crossref PubMed Scopus (5) Google Scholar, 33Ly M. Antoine M. Dembele A.K. Levy P. Rodenas A. Toure B.A. Badiaga Y. Dembele B.K. Bagayogo D.C. Diallo Y.L. Kone A.A. Callard P. Bernaudin J.F. Diallo D.A. High incidence of triple-negative tumors in sub-Saharan Africa: a prospective study of breast cancer characteristics and risk factors in Malian women seen in a Bamako university hospital.Oncology. 2012; 83: 257-263Crossref PubMed Scopus (281) Google Scholar, 34Der E.M. Gyasi R.K. Tettey Y. Edusei L. Bayor M.T. Jiagge E. Gyakobo M. Merajver S.D. Newman L.A. Triple-negative breast cancer in Ghanaian women: the Korle Bu Teaching Hospital experience.Breast J. 2015; 21: 627-633Crossref PubMed Scopus (52) Google Scholar, 35Ohene-Yeboah M. Adjei E. Breast cancer in Kumasi, Ghana.Ghana Med J. 2012; 46: 8-13Crossref PubMed Scopus (31) Google Scholar, 36Nwafor C.C. Keshinro S.O. Pattern of hormone receptors and human epidermal growth factor receptor 2 status in sub-Saharan breast cancer cases: private practice experience.Niger J Clin Pract. 2015; 18: 553-558PubMed Google Scholar, 37Proctor E. Kidwell K.M. Jiagge E. Bensenhaver J. Awuah B. Gyan K. Toy K. Oppong J.K. Kyei I. Aitpillah F. Osei-Bonsu E. Adjei E. Ohene-Yeboah M. Brewer R.N. Fondjo L.A. Owusu-Afriyie O. Wicha M. Merajver S. Kleer C. Newman L. Characterizing breast cancer in a population with increased prevalence of triple-negative breast cancer: androgen receptor and ALDH1 expression in Ghanaian women.Ann Surg Oncol. 2015; 22: 3831-3835Crossref PubMed Scopus (13) Google Scholar In contrast, the frequency of TNBC is <20% in many studies in patients from northern and eastern Africa.5Jiagge E. Jibril A.S. Chitale D. Bensenhaver J.M. Awuah B. Hoenerhoff M. Adjei E. Bekele M. Abebe E. Nathanson S.D. Gyan K. Salem B. Oppong J. Aitpillah F. Kyei I. Bonsu E.O. Proctor E. Merajver S.D. Wicha M. Stark A. Newman L.A. Comparative analysis of breast cancer phenotypes in African American, White American, and West versus East African patients: correlation between African ancestry and triple-negative breast cancer.Ann Surg Oncol. 2016; 23: 3843-3849Crossref PubMed Scopus (50) Google Scholar, 38Rais G. Raissouni S. Aitelhaj M. Rais F. Naciri S. Khoyaali S. Abahssain H. Bensouda Y. Khannoussi B. Mrabti H. Errihani H. Triple negative breast cancer in Moroccan women: clinicopathological and therapeutic study at the National Institute of Oncology.BMC Womens Health. 2012; 12: 35Crossref PubMed Scopus (24) Google Scholar, 39Bennis S. Abbass F. Akasbi Y. Znati K. Joutei K.A. El Mesbahi O. Amarti A. Prevalence of molecular subtypes and prognosis of invasive breast cancer in north-east of Morocco: retrospective study.BMC Res Notes. 2012; 5: 436Crossref PubMed Scopus (22) Google Scholar, 40Salhia B. Tapia C. Ishak E.A. Gaber S. Berghuis B. Hussain K.H. DuQuette R.A. Resau J. Carpten J. Molecular subtype analysis determines the association of advanced breast cancer in Egypt with favorable biology.BMC Womens Health. 2011; 11: 44Crossref PubMed Scopus (22) Google Scholar, 41Aiad H.A. Wahed M.M. Asaad N.Y. El-Tahmody M. Elhosary E. Immunohistochemical expression of GPR30 in breast carcinoma of Egyptian patients: an association with immunohistochemical subtypes.APMIS. 2014; 122: 976-984Crossref PubMed Scopus (46) Google Scholar The colonial-era trans-Atlantic slave trade resulted in the forced migration of Africans from the continent's gold coast to the Americas, resulting in shared ancestry between African Americans and western, sub-Saharan Africans42Campbell M.C. Hirbo J.B. Townsend J.P. Tishkoff S.A. The peopling of the African continent and the diaspora into the new world.Curr Opin Genet Dev. 2014; 29: 120-132Crossref PubMed Scopus (19) Google Scholar and potentially explaining similarities in breast cancer patterns in these two population subsets. TNBCs have morphologic growth patterns illustrating heterogeneity and highlighting distinctive biological features, clinical presentations, responses to therapy, and outcomes. There are several morphologic variants, with the high histologic grade invasive ductal carcinoma being the most common, associated with high mitotic rates, central necrotic or fibrotic zones, pushing borders, and conspicuous lymphocytic infiltrate. Other morphologies that are typically triple negative include medullary, secretory, and apocrine carcinomas—all of which have relatively more favorable biologic behaviors—and metaplastic carcinomas, which tend to be biologically more aggressive. This heterogeneous morphologic spectrum of subtypes is further supported and defined by diverse genetic pathways. Lehmann et al43Lehmann B.D. Bauer J.A. Chen X. Sanders M.E. Chakravarthy A.B. Shyr Y. Pietenpol J.A. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies.J Clin Invest. 2011; 121: 2750-2767Crossref PubMed Scopus (37) Google Scholar were among the early investigators identifying these triple-negative subtypes, and their efforts were based on analyses of gene-expression profiles from 21 publicly available data sets that included 587 TNBC cases. They identified six different subtypes—two basal-like subtypes, an immunomodulatory subtype, a mesenchymal subtype, a mesenchymal stem–like subtype, and a luminal androgen receptor subtype. Similarly, Burstein et al44Burstein M.D. Tsimelzon A. Poage G.M. Covington K.R. Contreras A. Fuqua S.A. Savage M.I. Osborne C.K. Hilsenbeck S.G. Chang J.C. Mills G.B. Lau C.C. Brown P.H. Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer.Clin Cancer Res. 2015; 21: 1688-1698Crossref PubMed Scopus (3440) Google Scholar identified four TNBC subtypes based on the gene-expression profiles of 198 cases from the Baylor College of Medicine (Houston, TX): i) a luminal androgen receptor subtype; ii) a mesenchymal subtype; iii) a basal-like immune-suppressed subtype; and iv) a basal-like immune-activated subtype. These different patterns have been shown to be associated with prognostic as well as predictive therapeutic value; the luminal androgen receptor subtype tends to respond poorly to neoadjuvant chemotherapy45Masuda H. Baggerly K.A. Wang Y. Zhang Y. Gonzalez-Angulo A.M. Meric-Bernstam F. Valero V. Lehmann B.D. Pietenpol J.A. Hortobagyi G.N. Symmans W.F. Ueno N.T. Differential response to neoadjuvant chemotherapy among 7 triple-negative breast cancer molecular subtypes.Clin Cancer Res. 2013; 19: 5533-5540Crossref PubMed Scopus (753) Google Scholar, 46Lehmann B.D. Jovanovic B. Chen X. Estrada M.V. Johnson K.N. Shyr Y. Moses H.L. Sanders M.E. Pietenpol J.A. Refinement of triple-negative breast cancer molecular subtypes: implications for neoadjuvant chemotherapy selection.PLoS One. 2016; 11: e0157368Crossref PubMed Scopus (507) Google Scholar and may be amenable to endocrine manipulation through anti-androgen therapy. Unfortunately, however, neither of these data sets included meaningful samples of triple-negative tumors from women of African ancestry. A few studies have provided limited but important findings with regard to gene-expression profiles of African-American breast cancer patients. Lindner et al47Lindner R. Sullivan C. Offor O. Lezon-Geyda K. Halligan K. Fischbach N. Shah M. Bossuyt V. Schulz V. Tuck D.P. Harris L.N. Molecular phenotypes in triple negative breast cancer from African American patients suggest targets for therapy.PLoS One. 2013; 8: e71915Crossref PubMed Scopus (686) Google Scholar evaluated 136 tumors f
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