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Reproductive risk factors for breast cancer and association with novel breast density measurements among Hispanic, Black, and White women

  • Epidemiology
  • Published:
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Abstract

Purpose

There are differences in the distributions of breast cancer incidence and risk factors by race and ethnicity. Given the strong association between breast density and breast cancer, it is of interest describe racial and ethnic variation in the determinants of breast density.

Methods

We characterized racial and ethnic variation in reproductive history and several measures of breast density for Hispanic (n = 286), non-Hispanic Black (n = 255), and non-Hispanic White (n = 1694) women imaged at a single hospital. We quantified associations between reproductive factors and percent volumetric density (PVD), dense volume (DV), non-dense volume (NDV), and a novel measure of pixel intensity variation (V) using multivariable-adjusted linear regression, and tested for statistical heterogeneity by race and ethnicity.

Results

Reproductive factors most strongly associated with breast density were age at menarche, parity, and oral contraceptive use. Variation by race and ethnicity was most evident for the associations between reproductive factors and NDV (minimum p-heterogeneity:0.008) and V (minimum p-heterogeneity:0.004) and least evident for PVD (minimum p-heterogeneity:0.042) and DV (minimum p-heterogeneity:0.041).

Conclusion

Reproductive choices, particularly those related to childbearing and oral contraceptive use, may contribute to racial and ethnic variation in breast density.

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Data availability

Study data may be shared upon reasonable request and with approval of the appropriate Institutional Review Boards.

References

  1. Siegel RL, Miller KD, Fuchs HE, Jemal A (2022) Cancer statistics, 2022. CA Cancer J Clin 72(1):7–33. https://doi.org/10.3322/caac.21708

    Article  PubMed  Google Scholar 

  2. Miller BA, Chu KC, Hankey BF, Ries LA (2008) Cancer incidence and mortality patterns among specific Asian and Pacific Islander populations in the U.S. Cancer Causes Control 19(3):227–56. https://doi.org/10.1007/s10552-007-9088-3

    Article  PubMed  Google Scholar 

  3. Pathak DR, Osuch JR, He J (2000) Breast carcinoma etiology: current knowledge and new insights into the effects of reproductive and hormonal risk factors in black and white populations. Cancer 88(5 Suppl):1230–1238. https://doi.org/10.1002/(SICI)1097-0142(20000301)88

    Article  CAS  PubMed  Google Scholar 

  4. Palmer JR, Wise LA, Horton NJ, Adams-Campbell LL, Rosenberg L (2003) Dual effect of parity on breast cancer risk in African-American women. J Natl Cancer Inst 95(6):478–483

    Article  PubMed  Google Scholar 

  5. Ursin G, Bernstein L, Wang Y, Lord SJ, Deapen D, Liff JM et al (2004) Reproductive factors and risk of breast carcinoma in a study of white and African-American women. Cancer 101(2):353–362. https://doi.org/10.1002/cncr.20373

    Article  PubMed  Google Scholar 

  6. Masi CM, Olopade OI (2005) Racial and ethnic disparities in breast cancer: a multilevel perspective. Med Clin North Am 89(4):753–770. https://doi.org/10.1016/j.mcna.2005.02.004

    Article  PubMed  Google Scholar 

  7. Warner ET, Tamimi RM, Boggs DA, Rosner B, Rosenberg L, Colditz GA et al (2013) Estrogen receptor positive tumors: do reproductive factors explain differences in incidence between black and white women? Cancer Causes Control 24(4):731–739. https://doi.org/10.1007/s10552-013-0153-9

    Article  PubMed  PubMed Central  Google Scholar 

  8. Bissell MCS, Kerlikowske K, Sprague BL, Tice JA, Gard CC, Tossas KY et al (2020) Breast cancer population attributable risk proportions associated with body mass index and breast density by race/ethnicity and menopausal status. Cancer Epidemiol Biomarkers Prev 29(10):2048–2056. https://doi.org/10.1158/1055-9965.EPI-20-0358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Barnard ME, Martheswaran T, Van Meter M, Buys SS, Curtin K, Doherty JA (2022) Body mass index and mammographic density in a multiracial and multiethnic population-based study. Cancer Epidemiol Biomarkers Prev 31(7):1313–1323. https://doi.org/10.1158/1055-9965.EPI-21-1249

    Article  PubMed  PubMed Central  Google Scholar 

  10. McCormack VA (2006) Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis. Cancer Epidemiol Biomark Prev 15(6):1159–1169. https://doi.org/10.1158/1055-9965.epi-06-0034

    Article  Google Scholar 

  11. Holowko N, Eriksson M, Kuja-Halkola R, Azam S, He W, Hall P et al (2020) Heritability of mammographic breast density, density change, microcalcifications, and masses. Cancer Res 80(7):1590–1600. https://doi.org/10.1158/0008-5472.CAN-19-2455

    Article  CAS  PubMed  Google Scholar 

  12. Grove JS, Goodman MJ, Gilbert FI Jr, Mi MP (1985) Factors associated with mammographic pattern. Br J Radiol 58(685):21–25. https://doi.org/10.1259/0007-1285-58-688-B21

    Article  CAS  PubMed  Google Scholar 

  13. Byrne C, Schairer C, Wolfe J, Parekh N, Salane M, Brinton LA et al (1995) Mammographic features and breast cancer risk: effects with time, age, and menopause status. J Natl Cancer Inst 87(21):1622–1629

    Article  CAS  PubMed  Google Scholar 

  14. Brisson J, Sadowsky NL, Twaddle JA, Morrison AS, Cole P, Merletti F (1982) The relation of mammographic features of the breast to breast cancer risk factors. Am J Epidemiol 115(3):438–443

    Article  CAS  PubMed  Google Scholar 

  15. Vachon CM, Kuni CC, Anderson K, Anderson VE, Sellers TA (2000) Association of mammographically defined percent breast density with epidemiologic risk factors for breast cancer (United States). Cancer Causes Control 11(7):653–662

    Article  CAS  PubMed  Google Scholar 

  16. Yaghjyan L, Mahoney MC, Succop P, Wones R, Buckholz J, Pinney SM (2012) Relationship between breast cancer risk factors and mammographic breast density in the Fernald Community Cohort. Br J Cancer 106(5):996–1003. https://doi.org/10.1038/bjc.2012.1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Harris HR, Tamimi RM, Willett WC, Hankinson SE, Michels KB (2011) Body size across the life course, mammographic density, and risk of breast cancer. Am J Epidemiol 174(8):909–918. https://doi.org/10.1093/aje/kwr225

    Article  PubMed  PubMed Central  Google Scholar 

  18. El-Bastawissi AY, White E, Mandelson MT, Taplin SH (2000) Reproductive and hormonal factors associated with mammographic breast density by age (United States). Cancer Causes Control 11(10):955–963

    Article  CAS  PubMed  Google Scholar 

  19. Boyd NF, Martin LJ, Sun L, Guo H, Chiarelli A, Hislop G et al (2006) Body size, mammographic density, and breast cancer risk. Cancer Epidemiol Biomark Prev 15(11):2086–2092. https://doi.org/10.1158/1055-9965.epi-06-0345

    Article  Google Scholar 

  20. Titus-Ernstoff L, Tosteson ANA, Kasales C, Weiss J, Goodrich M, Hatch EE et al (2006) Breast cancer risk factors in relation to breast density (United States). Cancer Causes Control 17(10):1281–1290. https://doi.org/10.1007/s10552-006-0071-1

    Article  PubMed  PubMed Central  Google Scholar 

  21. Moore JX, Han Y, Appleton C, Colditz G, Toriola AT (2020) Determinants of mammographic breast density by race among a large screening population. JNCI Cancer Spectr 4(2):pkaa010. https://doi.org/10.1093/jncics/pkaa010

    Article  PubMed  PubMed Central  Google Scholar 

  22. Alexeeff SE, Odo NU, McBride R, McGuire V, Achacoso N, Rothstein JH et al (2019) Reproductive factors and mammographic density: associations among 24,840 women and comparison of studies using digitized film-screen mammography and full-field digital mammography. Am J Epidemiol 188(6):1144–1154. https://doi.org/10.1093/aje/kwz033

    Article  PubMed  PubMed Central  Google Scholar 

  23. Alexeeff SE, Odo NU, Lipson JA, Achacoso N, Rothstein JH, Yaffe MJ et al (2017) Age at menarche and late adolescent adiposity associated with mammographic density on processed digital mammograms in 24,840 women. Cancer Epidemiol Biomarkers Prev 26(9):1450–1458. https://doi.org/10.1158/1055-9965.EPI-17-0264

    Article  PubMed  PubMed Central  Google Scholar 

  24. Ward SV, Burton A, Tamimi RM, Pereira A, Garmendia ML, Pollan M et al (2022) The association of age at menarche and adult height with mammographic density in the International Consortium of Mammographic Density. Breast Cancer Res 24(1):49. https://doi.org/10.1186/s13058-022-01545-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Jeffreys M, Warren R, Gunnell D, McCarron P, Smith GD (2004) Life course breast cancer risk factors and adult breast density (United Kingdom). Cancer Causes Control 15(9):947–955. https://doi.org/10.1007/s10522-004-2473-3

    Article  PubMed  Google Scholar 

  26. Rice MS, Bertrand KA, Lajous M, Tamimi RM, Torres G, Lopez-Ridaura R et al (2015) Reproductive and lifestyle risk factors and mammographic density in Mexican women. Ann Epidemiol 25(11):868–873. https://doi.org/10.1016/j.annepidem.2015.08.006

    Article  PubMed  PubMed Central  Google Scholar 

  27. Butler LM, Gold EB, Greendale GA, Crandall CJ, Modugno F, Oestreicher N et al (2008) Menstrual and reproductive factors in relation to mammographic density: the Study of Women’s Health Across the Nation (SWAN). Breast Cancer Res Treat 112(1):165–174. https://doi.org/10.1007/s10549-007-9840-0

    Article  PubMed  Google Scholar 

  28. Dorgan JF, Klifa C, Deshmukh S, Egleston BL, Shepherd JA, Kwiterovich PO et al (2013) Menstrual and reproductive characteristics and breast density in young women. Cancer Causes Control 24(11):1973–1983. https://doi.org/10.1007/s10552-013-0273-2

    Article  PubMed  PubMed Central  Google Scholar 

  29. McCormack VA, Perry N, Vinnicombe SJ, Silva IdS (2008) Ethnic variations in mammographic density: a British Multiethnic Longitudinal Study. Am J Epidemiol 168(4):412–21. https://doi.org/10.1093/aje/kwn169

    Article  PubMed  Google Scholar 

  30. Lope V, Pérez-Gómez B, Sánchez-Contador C, Santamariña MC, Moreo P, Vidal C et al (2012) Obstetric history and mammographic density: a population-based cross-sectional study in Spain (DDM-Spain). Breast Cancer Res Treat 132(3):1137–1146. https://doi.org/10.1007/s10549-011-1936-x

    Article  PubMed  PubMed Central  Google Scholar 

  31. van Duijnhoven FJB, Peeters PHM, Warren RML, Bingham SA, van Noord PAH, Monninkhof EM et al (2007) Postmenopausal hormone therapy and changes in mammographic density. J Clin Oncol 25(11):1323–1328. https://doi.org/10.1200/jco.2005.04.7332

    Article  PubMed  Google Scholar 

  32. Vachon CM, Sellers TA, Vierkant RA, Wu FF, Brandt KR (2002) Case-control study of increased mammographic breast density response to hormone replacement therapy. Cancer Epidemiol Biomarkers Prev 11(11):1382–1388

    CAS  PubMed  Google Scholar 

  33. Rutter CM (2001) Changes in breast density associated with initiation, discontinuation, and continuing use of hormone replacement therapy. JAMA 285(2):171. https://doi.org/10.1001/jama.285.2.171

    Article  CAS  PubMed  Google Scholar 

  34. McTiernan A, Martin CF, Peck JD, Aragaki AK, Chlebowski RT, Pisano ED et al (2005) Estrogen-plus-progestin use and mammographic density in postmenopausal women: women’s health initiative randomized trial. JNCI 97(18):1366–1376. https://doi.org/10.1093/jnci/dji279

    Article  CAS  PubMed  Google Scholar 

  35. Lundstrom E, Wilczek B, von Palffy Z, Soderqvist G, von Schoultz B (1999) Mammographic breast density during hormone replacement therapy: differences according to treatment. Am J Obstet Gynecol 181(2):348–352

    Article  CAS  PubMed  Google Scholar 

  36. Greendale GA, Reboussin BA, Slone S, Wasilauskas C, Pike MC, Ursin G (2003) Postmenopausal hormone therapy and change in mammographic density. J Natl Cancer Inst 95(1):30–37

    Article  CAS  PubMed  Google Scholar 

  37. Freedman M, San Martin J, O’Gorman J, Eckert S, Lippman ME, Lo SC et al (2001) Digitized mammography: a clinical trial of postmenopausal women randomly assigned to receive raloxifene, estrogen, or placebo. J Natl Cancer Inst 93(1):51–56

    Article  CAS  PubMed  Google Scholar 

  38. Highnam R, Brady SM, Yaffe MJ, Karssemeijer N, Harvey J. Robust Breast Composition Measurement - VolparaTM. Berlin, Heidelberg: Springer Berlin Heidelberg; 2010. p. 342–9.

  39. Heine JJ, Cao K, Rollison DE (2011) Calibrated measures for breast density estimation. Acad Radiol 18(5):547–555. https://doi.org/10.1016/j.acra.2010.12.007

    Article  PubMed  PubMed Central  Google Scholar 

  40. Heine JJ, Scott CG, Sellers TA, Brandt KR, Serie DJ, Wu FF et al (2012) A novel automated mammographic density measure and breast cancer risk. J Natl Cancer Inst 104(13):1028–1037. https://doi.org/10.1093/jnci/djs254

    Article  PubMed  PubMed Central  Google Scholar 

  41. Oh H, Rice MS, Warner ET, Bertrand KA, Fowler EE, Eliassen AH et al (2020) Early-life and adult anthropometrics in relation to mammographic image intensity variation in the Nurses’ Health Studies. Cancer Epidemiol Biomarkers Prev 29(2):343–351. https://doi.org/10.1158/1055-9965.EPI-19-0832

    Article  PubMed  Google Scholar 

  42. Heine J, Fowler E, Scott CG, Jensen MR, Shepherd J, Hruska CB et al (2021) Mammographic variation measures, breast density, and breast cancer risk. AJR Am J Roentgenol 217(2):326–335. https://doi.org/10.2214/AJR.20.22794

    Article  PubMed  PubMed Central  Google Scholar 

  43. Warner ET, Rice MS, Zeleznik OA, Fowler EE, Murthy D, Vachon CM et al (2021) Automated percent mammographic density, mammographic texture variation, and risk of breast cancer: a nested case-control study. NPJ Breast Cancer 7(1):68. https://doi.org/10.1038/s41523-021-00272-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Blair LK, Warner ET, James P, Hart JE, VoPham T, Barnard ME et al (2022) Exposure to natural vegetation in relation to mammographic density in a Massachusetts-based clinical cohort. Environ Epidemiol 6(4):e216. https://doi.org/10.1097/EE9.0000000000000216

    Article  PubMed  PubMed Central  Google Scholar 

  45. Highnam RP, Brady M, Yaffe MJ, Karssemeijer N, Harvey JA. Robust Breast Composition Measurement - VolparaTM. Digital Mammography/IWDM2010.

  46. Keller BM, Nathan DL, Wang Y, Zheng Y, Gee JC, Conant EF et al (2012) Estimation of breast percent density in raw and processed full field digital mammography images via adaptive fuzzy c-means clustering and support vector machine segmentation. Med Phys 39(8):4903–4917. https://doi.org/10.1118/1.4736530

    Article  PubMed  PubMed Central  Google Scholar 

  47. Eng A, Gallant Z, Shepherd J, McCormack V, Li J, Dowsett M et al (2014) Digital mammographic density and breast cancer risk: a case-control study of six alternative density assessment methods. Breast Cancer Res 16(5):439. https://doi.org/10.1186/s13058-014-0439-1

    Article  PubMed  PubMed Central  Google Scholar 

  48. del Carmen MG, Hughes KS, Halpern E, Rafferty E, Kopans D, Parisky YR et al (2003) Racial differences in mammographic breast density. Cancer 98(3):590–596. https://doi.org/10.1002/cncr.11517

    Article  PubMed  Google Scholar 

  49. Ellison-Loschmann L, McKenzie F, Highnam R, Cave A, Walker J, Jeffreys M (2013) Age and ethnic differences in volumetric breast density in New Zealand women: a cross-sectional study. PLoS ONE 8(7):e70217. https://doi.org/10.1371/journal.pone.0070217

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  50. Rajaram N, Mariapun S, Eriksson M, Tapia J, Kwan PY, Ho WK et al (2017) Differences in mammographic density between Asian and Caucasian populations: a comparative analysis. Breast Cancer Res Treat 161(2):353–362. https://doi.org/10.1007/s10549-016-4054-y

    Article  PubMed  Google Scholar 

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Funding

Researchers were supported in part by the National Cancer Institute of the National Institutes of Health via K00 CA212222 (MEB), T32 CA09001 (MEB, NCD) and K01 CA188075 (ETW), the Karin Grunebaum Cancer Research Foundation (MEB), the Dahod Breast Cancer Research Program of the Boston University School of Medicine (MEB), and the National Institute of Environmental Health Sciences of the National Institutes of Health via the University of Louisville Center for Integrative Environmental Health Sciences (CIEHS) P30 ES030283 (NCD). The contents of this manuscript are solely the responsibility of the authors. The funders played no role in study design, data collection, analysis and interpretation of data, or the writing of this manuscript.

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Author notes

  1. Erica T. Warner and Rulla M. Tamimi have contributed equally to this work.

Authors and Affiliations

  1. Slone Epidemiology Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, 02118, USA

    Mollie E. Barnard

  2. University of Utah Intermountain Healthcare Department of Population Health Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA

    Mollie E. Barnard

  3. Department of Epidemiology and Population Health, School of Public Health and Information Sciences, University of Louisville, Louisville, KY, USA

    Natalie C. DuPré

  4. Division of Population Sciences, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA

    John J. Heine & Erin E. Fowler

  5. Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Divya J. Murthy & Rebecca L. Nelleke

  6. Volpara Health Technologies Ltd., Wellington, New Zealand

    Ariane Chan

  7. Clinical Translational Epidemiology Unit, Department of Medicine, Mongan Institute, Massachusetts General Hospital, Boston, MA, USA

    Erica T. Warner

  8. Department of Population Health Sciences, Weill Cornell Medical, New York, NY, USA

    Rulla M. Tamimi

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  1. Mollie E. Barnard
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  7. Ariane Chan
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Contributions

All nine co-authors meet the authorship guidelines suggested by the International Committee of Medical Journal Editors. Seven co-authors contributed to the conception and design of the work (MEB, NCD, JJH, DJM, AC, ETW, RMT); six co-authors collected the data (MEB, NCD, JJH, EEF, DJM, AC); one co-author conducted the analyses and wrote the first draft of this manuscript (MEB); eight co-authors provided feedback on analyses and intellectually contributed to revision of the manuscript (NCD, JJH, EEF, DJM, AC, RLN, ETW, RMT), and two co-authors provided supervision at all stages of the project (ETW and RMT). All authors read and approved the final manuscript.

Corresponding author

Correspondence to Mollie E. Barnard.

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Competing Interests

Mollie E. Barnard reports personal fees from Epi Excellence LLC outside of the submitted work. Ariane Chan was an employee of Volpara Health Technologies Ltd. while contributing to this manuscript and holds shares in the company.

Ethical approval

All study procedures were approved by the Institutional Review Board at Brigham and Women’s Hospital of Mass General Brigham.

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All participants provided written informed consent to participate in the study.

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Barnard, M.E., DuPré, N.C., Heine, J.J. et al. Reproductive risk factors for breast cancer and association with novel breast density measurements among Hispanic, Black, and White women. Breast Cancer Res Treat 204, 309–325 (2024). https://doi.org/10.1007/s10549-023-07174-w

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