Breast cancer is a leading cause of cancer death in the world. The triple-negative breast cancer subtype is associated with poorer prognosis than hormone receptor-positive subtypes and is more prevalent among African Americans than white, European Americans. The goal of this study has been to elucidate environmental, hormonal, and cultural factors that may be contributing to this disparity in an effort to identify modifiable risk factors and improve triple-negative breast cancer outcomes. Factors that may impact risk include vitamin D defiency, hormonal factors, environmental and dietary exposure, radiation exposure, and obesity. These factors may disproportionately affect African American women as a result of socioeconomic status, lifestyle, and cultural norms. Furthermore, disparities in prognosis may be compounded by barriers such as access to healthcare, prevention education, and perceptions of healthcare. Both biological and sociocultural factors impacting risk must be addressed in order for future prevention and treatment efforts to succeed.
Mark A. Brown,
Cultural and Environmental Factors of Triple-Negative Breast Carcinomas, Cancer Research Journal.
Vol. 2, No. 2,
2014, pp. 18-28.
Society AC: Global Cancer Facts and Figures: 2nd Edition. 2011.
Society AC: Cancer Facts & Figures 2013. 2013.
Society AC: Breast Cancer Facts & Figures 2011-2012. 2012.
Stark A, Kleer CG, Martin I, Awuah B, Nsiah-Asare A, Takyi V, Braman M, Quayson SE, Zarbo R, Wicha M et al: African ancestry and higher prevalence of triple-negative breast cancer: findings from an international study. Cancer 2010, 116(21):4926-4932.
Pang J, Toy KA, Griffith KA, Awuah B, Quayson S, Newman LA, Kleer CG: Invasive breast carcinomas in Ghana: high frequency of high grade, basal-like histology and high EZH2 expression. Breast Cancer Res Treat 2012, 135(1):59-66.
Albain KS, Unger JM, Crowley JJ, Coltman CA, Jr., Hershman DL: Racial disparities in cancer survival among randomized clinical trials patients of the Southwest Oncology Group. J Natl Cancer Inst 2009, 101(14):984-992.
Griffiths CL, Olin JL: Triple negative breast cancer: a brief review of its characteristics and treatment options. Journal of pharmacy practice 2012, 25(3):319-323.
Yao S, Ambrosone CB: Associations between vitamin D deficiency and risk of aggressive breast cancer in African-American women. J Steroid Biochem Mol Biol 2012.
Dawood S: Triple-negative breast cancer: epidemiology and management options. Drugs 2010, 70(17):2247-2258.
Boyle P: Triple-negative breast cancer: epidemiological considerations and recommendations. Ann Oncol 2012, 23 Suppl 6:vi7-12.
Kwan ML, Kushi LH, Weltzien E, Maring B, Kutner SE, Fulton RS, Lee MM, Ambrosone CB, Caan BJ: Epidemiology of breast cancer subtypes in two prospective cohort studies of breast cancer survivors. Breast Cancer Res 2009, 11(3):R31.
Phipps AI, Malone KE, Porter PL, Daling JR, Li CI: Reproductive and hormonal risk factors for postmenopausal luminal, HER-2-overexpressing, and triple-negative breast cancer. Cancer 2008, 113(7):1521-1526.
Adisa CA, Eleweke N, Alfred AA, Campbell MJ, Sharma R, Nseyo O, Tandon V, Mukhtar R, Greninger A, Risi JD et al: Biology of breast cancer in Nigerian women: a pilot study. Ann Afr Med 2012, 11(3):169-175.
Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V: 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. Cancer 2007, 109(9):1721-1728.
Ma H, Wang Y, Sullivan-Halley J, Weiss L, Marchbanks PA, Spirtas R, Ursin G, Burkman RT, Simon MS, Malone KE et al: Use of four biomarkers to evaluate the risk of breast cancer subtypes in the women's contraceptive and reproductive experiences study. Cancer Res 2010, 70(2):575-587.
Brewster K, Wileyto EP, Kessler L, Collier A, Weathers B, Stopfer JE, Domchek S, Halbert CH: Sociocultural predictors of breast cancer risk perceptions in African American breast cancer survivors. Cancer Epidemiol Biomarkers Prev 2007, 16(2):244-248.
Coyle YM: The effect of environment on breast cancer risk. Breast Cancer Res Treat 2004, 84(3):273-288.
Tseng M, Byrne C, Evers KA, Daly MB: Dietary intake and breast density in high-risk women: a cross-sectional study. Breast Cancer Res 2007, 9(5):R72.
Garland CF, Gorham ED, Mohr SB, Grant WB, Giovannucci EL, Lipkin M, Newmark H, Holick MF, Garland FC: Vitamin D and prevention of breast cancer: pooled analysis. J Steroid Biochem Mol Biol 2007, 103(3-5):708-711.
Mohr SB, Gorham ED, Alcaraz JE, Kane CI, Macera CA, Parsons JK, Wingard DL, Garland CF: Does the evidence for an inverse relationship between serum vitamin D status and breast cancer risk satisfy the Hill criteria? Dermatoendocrinol 2012, 4(2):152-157.
Giovannucci E: Vitamin D and cancer incidence in the Harvard cohorts. Ann Epidemiol 2009, 19(2):84-88.
Pirianov G, Colston KW: Interaction of vitamin D analogs with signaling pathways leading to active cell death in breast cancer cells. Steroids 2001, 66(3-5):309-318.
Neuhouser ML, Sorensen B, Hollis BW, Ambs A, Ulrich CM, McTiernan A, Bernstein L, Wayne S, Gilliland F, Baumgartner K et al: Vitamin D insufficiency in a multiethnic cohort of breast cancer survivors. Am J Clin Nutr 2008, 88(1):133-139.
Lewis TJ, Dupont WD, Egan KM, Jones CD, Disher AC, Riddle WR, Fair AM: The "Got D'ViBE?" study: an inter-institutional project assessing vitamin D and mammographic breast density. J Health Care Poor Underserved 2010, 21(1 Suppl):17-25.
Bertone-Johnson ER, McTiernan A, Thomson CA, Wactawski-Wende J, Aragaki AK, Rohan TE, Vitolins MZ, Tamimi RM, Johnson KC, Lane D et al: Vitamin D and calcium supplementation and one-year change in mammographic density in the women's health initiative calcium and vitamin D trial. Cancer Epidemiol Biomarkers Prev 2012, 21(3):462-473.
Rozen F, Pollak M: Inhibition of insulin-like growth factor I receptor signaling by the vitamin D analogue EB1089 in MCF-7 breast cancer cells: A role for insulin-like growth factor binding proteins. Int J Oncol 1999, 15(3):589-594.
Suba Z: Light deficiency confers breast cancer risk by endocrine disorders. Recent Pat Anticancer Drug Discov 2012, 7(3):337-344.
Egan KM, Signorello LB, Munro HM, Hargreaves MK, Hollis BW, Blot WJ: Vitamin D insufficiency among African-Americans in the southeastern United States: implications for cancer disparities (United States). Cancer Causes Control 2008, 19(5):527-535.
Yao S, Zirpoli G, Bovbjerg DH, Jandorf L, Hong CC, Zhao H, Sucheston LE, Tang L, Roberts M, Ciupak G et al: Variants in the vitamin D pathway, serum levels of vitamin D, and estrogen receptor negative breast cancer among African-American women: a case-control study. Breast Cancer Res 2012, 14(2):R58.
Grant WB, Peiris AN: Differences in vitamin D status may account for unexplained disparities in cancer survival rates between African and white Americans. Dermatoendocrinol 2012, 4(2):85-94.
Macdonald HM: Contributions of sunlight and diet to vitamin D status. Calcif Tissue Int 2013, 92(2):163-176.
Wejse C, Olesen R, Rabna P, Kaestel P, Gustafson P, Aaby P, Andersen PL, Glerup H, Sodemann M: Serum 25-hydroxyvitamin D in a West African population of tuberculosis patients and unmatched healthy controls. Am J Clin Nutr 2007, 86(5):1376-1383.
Gerend MA, Pai M: Social determinants of Black-White disparities in breast cancer mortality: a review. Cancer Epidemiol Biomarkers Prev 2008, 17(11):2913-2923.
Flegal KM, Carroll MD, Kit BK, Ogden CL: Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010. Jama 2012, 307(5):491-497.
Garland CF, French CB, Baggerly LL, Heaney RP: Vitamin D supplement doses and serum 25-hydroxyvitamin D in the range associated with cancer prevention. Anticancer Res 2011, 31(2):607-611.
Phipps AI, Chlebowski RT, Prentice R, McTiernan A, Wactawski-Wende J, Kuller LH, Adams-Campbell LL, Lane D, Stefanick ML, Vitolins M et al: Reproductive history and oral contraceptive use in relation to risk of triple-negative breast cancer. J Natl Cancer Inst 2011, 103(6):470-477.
Palmer JR, Boggs DA, Wise LA, Ambrosone CB, Adams-Campbell LL, Rosenberg L: Parity and lactation in relation to estrogen receptor negative breast cancer in African American women. Cancer Epidemiol Biomarkers Prev 2011, 20(9):1883-1891.
Shinde SS, Forman MR, Kuerer HM, Yan K, Peintinger F, Hunt KK, Hortobagyi GN, Pusztai L, Symmans WF: Higher parity and shorter breastfeeding duration: association with triple-negative phenotype of breast cancer. Cancer 2010, 116(21):4933-4943.
Trivers KF, Lund MJ, Porter PL, Liff JM, Flagg EW, Coates RJ, Eley JW: The epidemiology of triple-negative breast cancer, including race. Cancer Causes Control 2009, 20(7):1071-1082.
Millikan RC, Newman B, Tse CK, Moorman PG, Conway K, Dressler LG, Smith LV, Labbok MH, Geradts J, Bensen JT et al: Epidemiology of basal-like breast cancer. Breast Cancer Res Treat 2008, 109(1):123-139.
Bulbul NH, Ozden S, Dayicioglu V: Effects of hormone replacement therapy on mammographic findings. Arch Gynecol Obstet 2003, 268(1):5-8.
Chen WY: Exogenous and endogenous hormones and breast cancer. Best Pract Res Clin Endocrinol Metab 2008, 22(4):573-585.
Spector D, Mishel M, Skinner CS, Deroo LA, Vanriper M, Sandler DP: Breast cancer risk perception and lifestyle behaviors among White and Black women with a family history of the disease. Cancer Nurs 2009, 32(4):299-308.
Dolle JM, Daling JR, White E, Brinton LA, Doody DR, Porter PL, Malone KE: Risk factors for triple-negative breast cancer in women under the age of 45 years. Cancer Epidemiol Biomarkers Prev 2009, 18(4):1157-1166.
Gupta PB, Proia D, Cingoz O, Weremowicz J, Naber SP, Weinberg RA, Kuperwasser C: Systemic stromal effects of estrogen promote the growth of estrogen receptor-negative cancers. Cancer Res 2007, 67(5):2062-2071.
Iyer V, Klebba I, McCready J, Arendt LM, Betancur-Boissel M, Wu MF, Zhang X, Lewis MT, Kuperwasser C: Estrogen promotes ER-negative tumor growth and angiogenesis through mobilization of bone marrow-derived monocytes. Cancer Res 2012, 72(11):2705-2713.
Parentes-Vieira J, Lopes-Costa P, Pires C, Dos Santos A, Pereira-Filho J, da Silva B: Quantification of angiogenesis in estrogen receptor-positive and negative breast carcinoma. Int Semin Surg Oncol 2007, 4:22.
Elkin M, Orgel A, Kleinman HK: An angiogenic switch in breast cancer involves estrogen and soluble vascular endothelial growth factor receptor 1. J Natl Cancer Inst 2004, 96(11):875-878.
Jian J, Yang Q, Dai J, Eckard J, Axelrod D, Smith J, Huang X: Effects of iron deficiency and iron overload on angiogenesis and oxidative stress-a potential dual role for iron in breast cancer. Free Radic Biol Med 2011, 50(7):841-847.
Wang CT, Chang WT, Yang TL: Study of the concentrations of calcium, copper, iron, magnesium and zinc in the hair of breast cancer patients. Trace Elements and Electrolytes 2006, 23(4):281-286.
Cui Y, Vogt S, Olson N, Glass AG, Rohan TE: Levels of zinc, selenium, calcium, and iron in benign breast tissue and risk of subsequent breast cancer. Cancer Epidemiol Biomarkers Prev 2007, 16(8):1682-1685.
Miller LD, Coffman LG, Chou JW, Black MA, Bergh J, D'Agostino R, Jr., Torti SV, Torti FM: An iron regulatory gene signature predicts outcome in breast cancer. Cancer Res 2011, 71(21):6728-6737.
Benbrahim-Tallaa L, Tokar EJ, Diwan BA, Dill AL, Coppin JF, Waalkes MP: Cadmium malignantly transforms normal human breast epithelial cells into a basal-like phenotype. Environ Health Perspect 2009, 117(12):1847-1852.
Gallagher CM, Chen JJ, Kovach JS: Environmental cadmium and breast cancer risk. Aging (Albany NY) 2010, 2(11):804-814.
Julin B, Wolk A, Bergkvist L, Bottai M, Akesson A: Dietary cadmium exposure and risk of postmenopausal breast cancer: a population-based prospective cohort study. Cancer Res 2012, 72(6):1459-1466.
McElroy JA, Shafer MM, Trentham-Dietz A, Hampton JM, Newcomb PA: Cadmium exposure and breast cancer risk. J Natl Cancer Inst 2006, 98(12):869-873.
Pasha Q, Malik SA, Iqbal J, Shaheen N, Shah MH: Screening of trace metals in the plasma of breast cancer patients in comparison with a healthy population. Human and Ecological Risk Assessment 2009, 15:1016-1032.
Saleh F, Behbehani A, Asfar S, Khan I, Ibrahim G: Abnormal blood levels of trace elements and metals, DNA damage, and breast cancer in the state of Kuwait. Biol Trace Elem Res 2011, 141(1-3):96-109.
Stawarz R, Formicki G, Zakrzewiski M, Rys J, Rozmus M: Distribution of heavy metals and trace elements in human breast cancer tissues and in adjacent normal tissues of women in Poland. Fresenius Environmental Bulletin 2009, 18(2):182-188.
Adams SV, Passarelli MN, Newcomb PA: Cadmium exposure and cancer mortality in the Third National Health and Nutrition Examination Survey cohort. Occup Environ Med 2012, 69(2):153-156.
Egwuogu H, Shendell DG, Okosun IS, Goodfellow L: The effect of urinary cadmium on cardiovascular fitness as measured by VO2 max in white, black and Mexican Americans. Environ Res 2009, 109(3):292-300.
Zhai H, Chen X, Hu Z: Study on the relationship between intake of trace elements and breast cancer mortality with chemometric methods. Comput Biol Chem 2003, 27(6):581-586.
Yang CY, Chiu HF, Cheng MF, Hsu TY, Cheng MF, Wu TN: Calcium and magnesium in drinking water and the risk of death from breast cancer. J Toxicol Environ Health A 2000, 60(4):231-241.
Barcellos-Hoff MH: New biological insights on the link between radiation exposure and breast cancer risk. J Mammary Gland Biol Neoplasia 2013, 18(1):3-13.
Lin NU, Vanderplas A, Hughes ME, Theriault RL, Edge SB, Wong YN, Blayney DW, Niland JC, Winer EP, Weeks JC: Clinicopathologic features, patterns of recurrence, and survival among women with triple-negative breast cancer in the National Comprehensive Cancer Network. Cancer 2012, 118(22):5463-5472.
Vona-Davis L, Rose DP: The influence of socioeconomic disparities on breast cancer tumor biology and prognosis: a review. J Womens Health (Larchmt) 2009, 18(6):883-893.
Kabat GC, Kim M, Phipps AI, Li CI, Messina CR, Wactawski-Wende J, Kuller L, Simon MS, Yasmeen S, Wassertheil-Smoller S et al: Smoking and alcohol consumption in relation to risk of triple-negative breast cancer in a cohort of postmenopausal women. Cancer Causes Control 2011, 22(5):775-783.
Sellers TA, Vierkant RA, Cerhan JR, Gapstur SM, Vachon CM, Olson JE, Pankratz VS, Kushi LH, Folsom AR: Interaction of dietary folate intake, alcohol, and risk of hormone receptor-defined breast cancer in a prospective study of postmenopausal women. Cancer Epidemiol Biomarkers Prev 2002, 11(10 Pt 1):1104-1107.
Brawley OW: Is race really a negative prognostic factor for cancer? J Natl Cancer Inst 2009, 101(14):970-971.
Chu QD, Henderson AE, Ampil F, Li BD: Outcome for patients with triple-negative breast cancer is not dependent on race/ethnicity. Int J Breast Cancer 2012, 2012:764570.
DeSantis C, Jemal A, Ward E: Disparities in breast cancer prognostic factors by race, insurance status, and education. Cancer Causes Control 2010, 21(9):1445-1450.
Dunn BK, Agurs-Collins T, Browne D, Lubet R, Johnson KA: Health disparities in breast cancer: biology meets socioeconomic status. Breast Cancer Res Treat 2010, 121(2):281-292.
Gordon NH: Association of education and income with estrogen receptor status in primary breast cancer. Am J Epidemiol 1995, 142(8):796-803.
Thomson CS, Hole DJ, Twelves CJ, Brewster DH, Black RJ: Prognostic factors in women with breast cancer: distribution by socioeconomic status and effect on differences in survival. J Epidemiol Community Health 2001, 55(5):308-315.
Mukhtar RA, Moore AP, Nseyo O, Baehner FL, Au A, Moore DH, Twomey P, Campbell MJ, Esserman LJ: Elevated PCNA+ tumor-associated macrophages in breast cancer are associated with early recurrence and non-Caucasian ethnicity. Breast Cancer Res Treat 2011, 130(2):635-644.
Avis-Williams A, Khoury A, Lisovicz N, Graham-Kresge S: Knowledge, attitudes, and practices of underserved women in the rural South toward breast cancer prevention and detection. Fam Community Health 2009, 32(3):238-246.
Fair AM, Monahan PO, Russell K, Zhao Q, Champion VL: The interaction of perceived risk and benefits and the relationship to predicting mammography adherence in African American women. Oncol Nurs Forum 2012, 39(1):53-60.
West DS, Greene PG, Kratt PP, Pulley L, Weiss HL, Siegfried N, Gore SA: The impact of a family history of breast cancer on screening practices and attitudes in low-income, rural, African American women. J Womens Health (Larchmt) 2003, 12(8):779-787.
Masi CM, Gehlert S: Perceptions of breast cancer treatment among African-American women and men: implications for interventions. J Gen Intern Med 2009, 24(3):408-414.
Haggstrom DA, Schapira MM: Black-white differences in risk perceptions of breast cancer survival and screening mammography benefit. J Gen Intern Med 2006, 21(4):371-377.
Hall AG, Khoury AJ, Lopez ED, Lisovicz N, Avis-Williams A, Mitra A: Breast cancer fatalism: the role of women's perceptions of the health care system. J Health Care Poor Underserved 2008, 19(4):1321-1335.
Spurlock WR, Cullins LS: Cancer fatalism and breast cancer screening in African American women. Abnf J 2006, 17(1):38-43.
Quach T, Nuru-Jeter A, Morris P, Allen L, Shema SJ, Winters JK, Le GM, Gomez SL: Experiences and perceptions of medical discrimination among a multiethnic sample of breast cancer patients in the Greater San Francisco Bay Area, California. Am J Public Health 2012, 102(5):1027-1034.
Song L, Hamilton JB, Moore AD: Patient-healthcare provider communication: perspectives of African American cancer patients. Health Psychol 2012, 31(5):539-547.