Abstract
Purpose
Breast cancer is a heterogeneous disease, with at least five intrinsic subtypes defined by molecular characteristics. Tumors that express the estrogen receptor (ER+) have better outcomes than ER− tumors, due in part to the success of hormonal therapies that target ER+ tumors. The incidence of ER− breast cancer, and the subset of ER− cancers that are basal-like, is about twice as high among African American (AA) women as among US women of European descent (EA). This disparity appears to explain, in part, the disproportionately high mortality from breast cancer that occurs in AA women. Epidemiologic research on breast cancer in AA women lags behind research in EA women. Here, we review differences in the etiology of breast cancer subtypes among AA women and describe a new consortium of ongoing studies of breast cancer in AA women.
Methods
We combined samples and data from four large epidemiologic studies of breast cancer in AA women, two cohort and two case-control, creating the African American Breast Cancer Epidemiology and Risk consortium. Tumor tissue is obtained and stored in tissue microarrays, with assays of molecular markers carried out at a pathology core. Genotyping, carried out centrally, includes a whole exome SNP array and over 180,000 custom SNPs for fine-mapping of genome-wide association studies loci and candidate pathways.
Results
To date, questionnaire data from 5,739 breast cancer cases and 14,273 controls have been harmonized. Genotyping of the first 3,200 cases and 3,700 controls is underway, with a total of 6,000 each expected by the end of the study period.
Conclusions
The new consortium will likely have sufficient statistical power to assess potential risk factors, both genetic and non-genetic, in relation to specific subtypes of breast cancer in AA women.
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Parker JS, Mullins M, Cheang MC et al (2009) Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol 27(8):1160–1167
Perou CM, Sorlie T, Eisen MB et al (2000) Molecular portraits of human breast tumours. Nature 406(6797):747–752
Goss PE, Ingle JN, Martino S et al (2007) Efficacy of letrozole extended adjuvant therapy according to estrogen receptor and progesterone receptor status of the primary tumor: National Cancer Institute of Canada Clinical Trials Group MA.17. J Clin Oncol 25(15):2006–2011
Berry DA, Cirrincione C, Henderson IC et al (2006) Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. JAMA 295(14):1658–1667
Burstein HJ, Prestrud AA, Seidenfeld J et al (2010) American Society of Clinical Oncology clinical practice guideline: update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. J Clin Oncol 28(23):3784–3796
Bardou VJ, Arpino G, Elledge RM et al (2003) Progesterone receptor status significantly improves outcome prediction over estrogen receptor status alone for adjuvant endocrine therapy in two large breast cancer databases. J Clin Oncol 21(10):1973–1979
Jemal A, Ward E, Thun MJ (2007) Recent trends in breast cancer incidence rates by age and tumor characteristics among US women. Breast Cancer Res 9(3):R28
Anderson WF, Chatterjee N, Ershler WB et al (2002) Estrogen receptor breast cancer phenotypes in the surveillance, epidemiology, and end results database. Breast Cancer Res Treat 76(1):27–36
Chu KC, Anderson WF (2002) Rates for breast cancer characteristics by estrogen and progesterone receptor status in the major racial/ethnic groups. Breast Cancer Res Treat 74(3):199–211
Furberg H, Millikan R, Dressler L et al (2001) Tumor characteristics in African American and white women. Breast Cancer Res Treat 68(1):33–43
Gapstur SM, Dupuis J, Gann P et al (1996) Hormone receptor status of breast tumors in black, Hispanic, and non-Hispanic white women. An analysis of 13,239 cases. Cancer 77(8):1465–1471
Joslyn SA (2002) Racial differences in treatment and survival from early-stage breast carcinoma. Cancer 95(8):1759–1766
Amend K, Hicks D, Ambrosone CB (2006) Breast cancer in African-American women: differences in tumor biology from European-American women. Cancer Res 66(17):8327–8330
Chlebowski RT, Chen Z, Anderson GL et al (2005) Ethnicity and breast cancer: factors influencing differences in incidence and outcome. J Natl Cancer Inst 97(6):439–448
Yang XR, Sherman ME, Rimm DL et al (2007) Differences in risk factors for breast cancer molecular subtypes in a population-based study. Cancer Epidemiol Biomarkers Prev 16(3):439–443
Kim MJ, Ro JY, Ahn SH et al (2006) Clinicopathologic significance of the basal-like subtype of breast cancer: a comparison with hormone receptor and Her2/neu-overexpressing phenotypes. Hum Pathol 37(9):1217–1226
Kurebayashi J, Moriya T, Ishida T et al (2007) The prevalence of intrinsic subtypes and prognosis in breast cancer patients of different races. Breast 16(Suppl 2):S72–S77
Lin CH, Liau JY, Lu YS et al (2009) Molecular subtypes of breast cancer emerging in young women in Taiwan: evidence for more than just westernization as a reason for the disease in Asia. Cancer Epidemiol Biomarkers Prev 18(6):1807–1814
Bauer KR, Brown M, Cress RD et al (2007) 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 109(9):1721–1728
Carey LA, Perou CM, Livasy CA et al (2006) Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA 295(21):2492–2502
Cheang MC, Chia SK, Voduc D et al (2009) Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst 101(10):736–750
Cheang MC, Voduc D, Bajdik C et al (2008) Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin Cancer Res 14(5):1368–1376
Millikan RC, Newman B, Tse CK et al (2008) Epidemiology of basal-like breast cancer. Breast Cancer Res Treat 109(1):123–139
Yang XR, Chang-Claude J, Goode EL et al (2011) Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies. J Natl Cancer Inst 103(3):250–263
Palmer JR, Adams-Campbell LL, Boggs DA et al (2007) A prospective study of body size and breast cancer in black women. Cancer Epidemiol Biomarkers Prev 16(9):1795–1802
Trivers KF, Lund MJ, Porter PL et al (2009) The epidemiology of triple-negative breast cancer, including race. Cancer Causes Control 20(7):1071–1082
Schatzkin A, Palmer JR, Rosenberg L et al (1987) Risk factors for breast cancer in black women. J Natl Cancer Inst 78(2):213–217
Ogundiran TO, Huo D, Adenipekun A et al (2010) Case-control study of body size and breast cancer risk in Nigerian women. Am J Epidemiol 172(6):682–690
Palmer JR, Boggs DA, Wise LA et al (2011) Parity and lactation in relation to estrogen receptor negative breast cancer in African American women. Cancer Epidemiol Biomarkers Prev 20(9):1883–1891
Phipps AI, Chlebowski RT, Prentice R et al (2011) Reproductive history and oral contraceptive use in relation to risk of triple-negative breast cancer. J Natl Cancer Inst 103(6):470–477
Kwan ML, Kushi LH, Weltzien E et al (2009) Epidemiology of breast cancer subtypes in two prospective cohort studies of breast cancer survivors. Breast Cancer Res 11(3):R31
Shinde SS, Forman MR, Kuerer HM et al (2010) Higher parity and shorter breastfeeding duration: association with triple-negative phenotype of breast cancer. Cancer 116(21):4933–4943
Schedin P (2006) Pregnancy-associated breast cancer and metastasis. Nat Rev Cancer 6(4):281–291
Ma H, Bernstein L, Ross RK et al (2006) Hormone-related risk factors for breast cancer in women under age 50 years by estrogen and progesterone receptor status: results from a case-control and a case–case comparison. Breast Cancer Res 8(4):R39
Rosenberg L, Boggs DA, Wise LA et al (2010) Oral contraceptive use and estrogen/progesterone receptor-negative breast cancer among African American women. Cancer Epidemiol Biomarkers Prev 19(8):2073–2079
Bernstein L, Teal CR, Joslyn S et al (2003) Ethnicity-related variation in breast cancer risk factors. Cancer 97(1 Suppl):222–229
Kim SY, Dietz PM, England L et al (2007) Trends in pre-pregnancy obesity in nine states, 1993–2003. Obesity (Silver Spring) 15(4):986–993
Ogden CL, Carroll MD, Curtin LR et al (2006) Prevalence of overweight and obesity in the United States, 1999–2004. JAMA 295(13):1549–1555
Harvie M, Hooper L, Howell AH (2003) Central obesity and breast cancer risk: a systematic review. Obes Rev 4(3):157–173
Okosun IS, Chandra KM, Boev A et al (2004) Abdominal adiposity in US adults: prevalence and trends, 1960–2000. Prev Med 39(1):197–206
National Institutes of Health/National Heart Lung and Blood (1998) Clinical Guidelines on identification, evaluation, and treatment of overweight and obesity in adults. The evidence report. Obes Res 6:51S–209S
National task force on the prevention and treatment of obesity (2000) Overweight, obesity, and health risk. Arch Intern Med 160(7):898–904
Flegal KM, Graubard BI, Williamson DF et al (2005) Excess deaths associated with underweight, overweight, and obesity. JAMA 293(15):1861–1867
Ballard-Barbash R (1994) Anthropometry and breast cancer. Body size—a moving target. Cancer 74(3 Suppl):1090–1100
Despres JP (1993) Abdominal obesity as important component of insulin-resistance syndrome. Nutrition 9(5):452–459
Kirschner MA, Samojlik E, Drejka M et al (1990) Androgen-estrogen metabolism in women with upper body versus lower body obesity. J Clin Endocrinol Metab 70(2):473–479
Kissebah AH, Krakower GR (1994) Regional adiposity and morbidity. Physiol Rev 74(4):761–811
Okosun IS, Boltri JM, Anochie LK et al (2004) Racial/ethnic differences in prehypertension in American adults: population and relative attributable risks of abdominal obesity. J Hum Hypertens 18(12):849–855
Stevens J (1995) Obesity, fat patterning and cardiovascular risk. Adv Exp Med Biol 369:21–27
Hall IJ, Newman B, Millikan RC et al (2000) Body size and breast cancer risk in black women and white women: the Carolina Breast Cancer Study. Am J Epidemiol 151(8):754–764
Lahmann PH, Hoffmann K, Allen N et al (2004) Body size and breast cancer risk: findings from the European Prospective Investigation into Cancer and Nutrition (EPIC). Int J Cancer 111(5):762–771
van den Brandt PA, Spiegelman D, Yaun SS et al (2000) Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk. Am J Epidemiol 152(6):514–527
Connolly BS, Barnett C, Vogt KN et al (2002) A meta-analysis of published literature on waist-to-hip ratio and risk of breast cancer. Nutr Cancer 44(2):127–138
Althuis MD, Fergenbaum JH, Garcia-Closas M et al (2004) Etiology of hormone receptor-defined breast cancer: a systematic review of the literature. Cancer Epidemiol Biomarkers Prev 13(10):1558–1568
Colditz GA, Rosner BA, Chen WY et al (2004) Risk factors for breast cancer according to estrogen and progesterone receptor status. J Natl Cancer Inst 96(3):218–228
Setiawan VW, Monroe KR, Wilkens LR et al (2009) Breast cancer risk factors defined by estrogen and progesterone receptor status: the multiethnic cohort study. Am J Epidemiol 169(10):1251–1259
Adams-Campbell LL, Kim KS, Dunston G et al (1996) The relationship of body mass index to reproductive factors in pre- and postmenopausal African-American women with and without breast cancer. Obes Res 4(5):451–456
Austin H, Cole P, Wynder E (1979) Breast cancer in black American women. Int J Cancer 24(5):541–544
Zhu K, Caulfield J, Hunter S et al (2005) Body mass index and breast cancer risk in African American women. Ann Epidemiol 15(2):123–128
Berstad P, Coates RJ, Bernstein L et al (2010) A case-control study of body mass index and breast cancer risk in white and African-American women. Cancer Epidemiol Biomarkers Prev 19(6):1532–1544
Sachdev D, Yee D (2001) The IGF system and breast cancer. Endocr Relat Cancer 8(3):197–209
Hankinson SE, Schernhammer ES (2003) Insulin-like growth factor and breast cancer risk: evidence from observational studies. Breast Dis 17:27–40
Wiseman M (2008) The second World Cancer Research Fund/American Institute for Cancer Research expert report. Food, nutrition, physical activity, and the prevention of cancer: a global perspective. Proc Nutr Soc 67(3):253–256
Friedenreich CM, Cust AE (2008) Physical activity and breast cancer risk: impact of timing, type and dose of activity and population subgroup effects. Br J Sports Med 42(8):636–647
McTiernan A, Kooperberg C, White E et al (2003) Recreational physical activity and the risk of breast cancer in postmenopausal women: the Women’s Health Initiative Cohort Study. JAMA 290(10):1331–1336
Dallal CM, Sullivan-Halley J, Ross RK et al (2007) Long-term recreational physical activity and risk of invasive and in situ breast cancer: the California teachers study. Arch Intern Med 167(4):408–415
Bernstein L, Patel AV, Ursin G et al (2005) Lifetime recreational exercise activity and breast cancer risk among black women and white women. J Natl Cancer Inst 97(22):1671–1679
Peters TM, Schatzkin A, Gierach GL et al (2009) Physical activity and postmenopausal breast cancer risk in the NIH-AARP diet and health study. Cancer Epidemiol Biomarkers Prev 18(1):289–296
Adams SA, Matthews CE, Hebert JR et al (2006) Association of physical activity with hormone receptor status: the Shanghai Breast Cancer Study. Cancer Epidemiol Biomarkers Prev 15(6):1170–1178
Bardia A, Hartmann LC, Vachon CM et al (2006) Recreational physical activity and risk of postmenopausal breast cancer based on hormone receptor status. Arch Intern Med 166(22):2478–2483
Enger SM, Ross RK, Paganini-Hill A et al (2000) Body size, physical activity, and breast cancer hormone receptor status: results from two case-control studies. Cancer Epidemiol Biomarkers Prev 9(7):681–687
Palmer JR, Ruiz-Narvaez EA, Rotimi CN et al (2013) Genetic susceptibility loci for subtypes of breast cancer in an African American population. Cancer Epidemiol Biomarkers Prev 22(1):127–134
Fejerman L, Haiman CA, Reich D et al (2009) An admixture scan in 1,484 African American women with breast cancer. Cancer Epidemiol Biomarkers Prev 18(11):3110–3117
Nesby-O’Dell S, Scanlon KS, Cogswell ME et al (2002) Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988–1994. Am J Clin Nutr 76(1):187–192
Ginde AA, Liu MC, Camargo CA Jr (2009) Demographic differences and trends of vitamin D insufficiency in the US population, 1988–2004. Arch Intern Med 169(6):626–632
Yao S, Zirpoli G, Bovbjerg DH et al (2012) 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 14(2):R58
Bauer SR, Hankinson SE, Bertone-Johnson ER et al (2013) Plasma vitamin D levels, menopause, and risk of breast cancer: dose-response meta-analysis of prospective studies. Medicine (Baltimore) 92(3):123–131
Yao S, Sucheston LE, Millen AE et al (2011) Pretreatment serum concentrations of 25-hydroxyvitamin D and breast cancer prognostic characteristics: a case-control and a case-series study. PLoS ONE 6(2):e17251
Peppone LJ, Rickles AS, Janelsins MC et al (2012) The association between breast cancer prognostic indicators and serum 25-OH vitamin D levels. Ann Surg Oncol 19(8):2590–2599
Rainville C, Khan Y, Tisman G (2009) Triple negative breast cancer patients presenting with low serum vitamin D levels: a case series. Cases J 2:8390
Kawase T, Matsuo K, Suzuki T et al (2010) Association between vitamin D and calcium intake and breast cancer risk according to menopausal status and receptor status in Japan. Cancer Sci 101(5):1234–1240
Eliassen AH, Spiegelman D, Hollis BW et al (2011) Plasma 25-hydroxyvitamin D and risk of breast cancer in the Nurses’ Health Study II. Breast Cancer Res 13(3):R50
Blackmore KM, Lesosky M, Barnett H et al (2008) Vitamin D from dietary intake and sunlight exposure and the risk of hormone-receptor-defined breast cancer. Am J Epidemiol 168(8):915–924
Heikkila K, Ebrahim S, Lawlor DA (2007) A systematic review of the association between circulating concentrations of C reactive protein and cancer. J Epidemiol Community Health 61(9):824–833
Gong Z, Quan L, Yao S et al (2013) Innate immunity pathways and breast cancer risk in African American and European-American women in the Women’s Circle of Health Study (WCHS). PLoS One 8(8):e72619
Quan L, Gong Z, Yao S et al (2013) Cytokine and cytokine receptor genes of adaptive immune response are differentially associated with breast cancer risk in American women of African and European ancestry. Int J Cancer. doi:10.1002/ijc.28458
Pierce BL, Ballard-Barbash R, Bernstein L et al (2009) Elevated biomarkers of inflammation are associated with reduced survival among breast cancer patients. J Clin Oncol 27(21):3437–3444
Lyon DE, McCain NL, Walter J et al (2008) Cytokine comparisons between women with breast cancer and women with a negative breast biopsy. Nurs Res 57(1):51–58
Rao VS, Dyer CE, Jameel JK et al (2006) Potential prognostic and therapeutic roles for cytokines in breast cancer (Review). Oncol Rep 15(1):179–185
Ness RB, Haggerty CL, Harger G et al (2004) Differential distribution of allelic variants in cytokine genes among African Americans and White Americans. Am J Epidemiol 160(11):1033–1038
Zabaleta J, Schneider BG, Ryckman K et al (2008) Ethnic differences in cytokine gene polymorphisms: potential implications for cancer development. Cancer Immunol Immunother 57(1):107–114
Kwiatkowski DP (2005) How malaria has affected the human genome and what human genetics can teach us about malaria. Am J Hum Genet 77(2):171–192
Campbell MC, Tishkoff SA (2008) African genetic diversity: implications for human demographic history, modern human origins, and complex disease mapping. Annu Rev Genomics Hum Genet 9:403–433
Shen H, Schuster R, Stringer KF et al (2006) The Duffy antigen/receptor for chemokines (DARC) regulates prostate tumor growth. FASEB J 20(1):59–64
Hong CC, Yao S, McCann SE et al (2013) Pretreatment levels of circulating Th1 and Th2 cytokines, and their ratios, are associated with ER-negative and triple negative breast cancers. Breast Cancer Res Treat 139(2):477–488
Chen F, Chen GK, Millikan RC et al (2011) Fine-mapping of breast cancer susceptibility loci characterizes genetic risk in African Americans. Hum Mol Genet 20(22):4491–4503
Chen F, Chen GK, Stram DO et al (2013) A genome-wide association study of breast cancer in women of African ancestry. Hum Genet 132(1):39–48
Huo D, Zheng Y, Ogundiran TO et al (2012) Evaluation of 19 susceptibility loci of breast cancer in women of African ancestry. Carcinogenesis 33(4):835–840
Michailidou K, Hall P, Gonzalez-Neira A et al (2013) Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Nat Genet 45(4):353–361, 361e1-2
Garcia-Closas M, Couch FJ, Lindstrom S et al (2013) Genome-wide association studies identify four ER negative-specific breast cancer risk loci. Nat Genet 45(4):392–398, 398e1-2
Zheng W, Cai Q, Signorello LB et al (2009) Evaluation of 11 breast cancer susceptibility loci in African-American women. Cancer Epidemiol Biomarkers Prev 18(10):2761–2764
Ruiz-Narvaez EA, Rosenberg L, Rotimi CN et al (2010) Genetic variants on chromosome 5p12 are associated with risk of breast cancer in African American women: the Black Women’s Health Study. Breast Cancer Res Treat 123(2):525–530
Hutter CM, Young AM, Ochs-Balcom HM et al (2011) Replication of breast cancer GWAS susceptibility loci in the Women’s Health Initiative African American SHARe Study. Cancer Epidemiol Biomarkers Prev 20(9):1950–1959
Haiman CA, Chen GK, Vachon CM et al (2011) A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer. Nat Genet 43(12):1210–1214
Newman B, Moorman PG, Millikan R et al (1995) The Carolina Breast Cancer Study: integrating population-based epidemiology and molecular biology. Breast Cancer Res Treat 35(1):51–60
McGee SA, Durham DD, Tse CK et al (2013) Determinants of breast cancer treatment delay differ for African American and white women. Cancer Epidemiol Biomarkers Prev 22(7):1227–1238
Ambrosone CB, Ciupak GL, Bandera EV et al (2009) Conducting molecular epidemiological research in the age of HIPAA: a multi-institutional case-control study of breast cancer in African-American and European-American Women. J Oncol 2009:871250
Bandera EV, Chandran U, Zirpoli G et al (2013) Rethinking sources of representative controls for the conduct of case-control studies in minority populations. BMC Med Res Methodol 13:71
Rosenberg L, Rao RS, Palmer JR (2003) A case-control study of acetaminophen use in relation to the risk of first myocardial infarction in men. Pharmacoepidemiol Drug Saf 12(6):459–465
Cozier YC, Palmer JR, Rosenberg L (2004) Comparison of methods for collection of DNA samples by mail in the Black Women’s Health Study. Ann Epidemiol 14(2):117–122
Kolonel LN, Henderson BE, Hankin JH et al (2000) A multiethnic cohort in Hawaii and Los Angeles: baseline characteristics. Am J Epidemiol 151(4):346–357
Khoury MJ, Wacholder S (2009) Invited commentary: from genome-wide association studies to gene-environment-wide interaction studies—challenges and opportunities. Am J Epidemiol 169(2):227–230; discussion 234–235
Acknowledgments
The authors wish to acknowledge the late Robert Millikan for his dedication to preventing breast cancer in African American women and for his thoughtfulness and energy in building this consortium. We also acknowledge the many AMBER consortium investigators who have contributed substantially to the inception and design of the original studies and working on the collaboration, in particular Lynn Rosenberg, Laurence Kolonel, Kathryn Lunetta, Chi-Chen Hong, Song Yao, Song Liu, Edward Ruiz-Narvaez, Traci Bethea, Patricia Coogan, Christopher Haiman, Melissa Troester, Jeannette Bensen, Nicholas Taylor, Mary Beth Bell, Patricia Basta, H. Shelton Earp, Warren Davis, Gary Zirpoli, Joseph Geradts, Wiam Bshara, Thaer Khoury, Stephanie Cohen, Gregory Ciupak, and Meghan O’Connor.
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Palmer, J.R., Ambrosone, C.B. & Olshan, A.F. A collaborative study of the etiology of breast cancer subtypes in African American women: the AMBER consortium. Cancer Causes Control 25, 309–319 (2014). https://doi.org/10.1007/s10552-013-0332-8
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DOI: https://doi.org/10.1007/s10552-013-0332-8