Skip to main content

Advertisement

SpringerLink
Log in

A review of the influence of mammographic density on breast cancer clinical and pathological phenotype

  • Review
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

It is well established that high mammographic density (MD), when adjusted for age and body mass index, is one of the strongest known risk factors for breast cancer (BC), and also associates with higher incidence of interval cancers in screening due to the masking of early mammographic abnormalities. Increasing research is being undertaken to determine the underlying histological and biochemical determinants of MD and their consequences for BC pathogenesis, anticipating that improved mechanistic insights may lead to novel preventative or treatment interventions. At the same time, technological advances in digital and contrast mammography are such that the validity of well-established relationships needs to be re-examined in this context.

Methods

With attention to old versus new technologies, we conducted a literature review to summarise the relationships between clinicopathologic features of BC and the density of the surrounding breast tissue on mammography, including the associations with BC biological features inclusive of subtype, and implications for the clinical disease course encompassing relapse, progression, treatment response and survival.

Results and conclusions

There is reasonable evidence to support positive relationships between high MD (HMD) and tumour size, lymph node positivity and local relapse in the absence of radiotherapy, but not between HMD and LVI, regional relapse or distant metastasis. Conflicting data exist for associations of HMD with tumour location, grade, intrinsic subtype, receptor status, second primary incidence and survival, which need further confirmatory studies. We did not identify any relationships that did not hold up when data involving newer imaging techniques were employed in analysis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. American Cancer Society (2019) Cancer Facts & Figures

  2. Sak MA, Littrup PJ, Duric N, Mullooly M, Sherman ME, Gierach GL (2015) Current and future methods for measuring breast density: a brief comparative review. Breast Cancer Manag 4(4):209–221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Hugo HJ, Tourell MC, O’Gorman PM, et al (2018) Looking beyond the mammogram to assess mammographic density: A narrative review. Biomedical Spectroscopy and Imaging. (Preprint):1–18

  4. Boyd NF, Guo H, Martin LJ et al (2007) Mammographic density and the risk and detection of breast cancer. N Engl J Med 356(3):227–236

    Article  CAS  PubMed  Google Scholar 

  5. Rauh C, Hack CC, Häberle L et al (2012) Percent mammographic density and dense area as risk factors for breast cancer. Geburtshilfe Frauenheilkd 72(8):727–733

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Wolfe JN (1976) Risk for breast cancer development determined by mammographic parenchymal pattern. Cancer 37(5):2486–2492

    Article  CAS  PubMed  Google Scholar 

  7. Egan RL, Mosteller RC (1977) Breast cancer mammography patterns. Cancer 40(5):2087–2090

    Article  CAS  PubMed  Google Scholar 

  8. Veronesi U, Boyle P, Goldhirsch A, Orecchia R, Viale G (2005) Breast cancer. Lancet 365(9472):1727–1741

    Article  PubMed  Google Scholar 

  9. McCormack VA, dos Santos Silva I (2006) Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis. Cancer Epidemiol Biomark Prev 15(6):1159–1169

    Article  Google Scholar 

  10. Hopper JL (2015) Odds per adjusted standard deviation: comparing strengths of associations for risk factors measured on different scales and across diseases and populations. Am J Epidemiol 182(10):863–867

    Article  PubMed  PubMed Central  Google Scholar 

  11. Krishnan K, Baglietto L, Apicella C et al (2016) Mammographic density and risk of breast cancer by mode of detection and tumor size: a case-control study. Breast Cancer Res 18:63

    Article  PubMed  PubMed Central  Google Scholar 

  12. Ghosh K, Vachon CM, Pankratz VS et al (2010) Independent association of lobular involution and mammographic breast density with breast cancer risk. J Natl Cancer Inst 102(22):1716–1723

    Article  PubMed  PubMed Central  Google Scholar 

  13. Mitchell G, Antoniou AC, Warren R et al (2006) Mammographic density and breast cancer risk in BRCA1 and BRCA2 mutation carriers. Cancer Res 66(3):1866–1872

    Article  CAS  PubMed  Google Scholar 

  14. Martin LJ, Melnichouk O, Guo H et al (2010) Family history, mammographic density, and risk of breast cancer. Cancer Epidemiol Biomark Prev 19(2):456–463

    Article  Google Scholar 

  15. Sung H, Ren J, Li J et al (2018) Breast cancer risk factors and mammographic density among high-risk women in urban China. NPJ breast cancer. 4(1):3

    Article  PubMed  PubMed Central  Google Scholar 

  16. Huo CW, Chew GL, Britt KL et al (2014) Mammographic density-a review on the current understanding of its association with breast cancer. Breast Cancer Res Treat 144(3):479–502

    Article  CAS  PubMed  Google Scholar 

  17. Mullooly M, Pfeiffer RM, Nyante SJ et al (2016) Mammographic density as a biosensor of tamoxifen effectiveness in adjuvant endocrine treatment of breast cancer: opportunities and implications. J Clin Oncol 34(18):2093–2097

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Shawky MS, Martin H, Hugo HJ et al (2017) Mammographic density: a potential monitoring biomarker for adjuvant and preventative breast cancer endocrine therapies. Oncotarget 8(3):5578–5591

    Article  PubMed  Google Scholar 

  19. Hassanzadeh J, Moradzadeh R, Rajaee Fard A, Tahmasebi S, Golmohammadi P (2012) A comparison of case-control and case-only designs to investigate gene-environment interactions using breast cancer data. Iran J Med Sci 37(2):112–118

    PubMed  PubMed Central  Google Scholar 

  20. Harvey JA (2004) Quantitative assessment of percent breast density: analog versus digital acquisition. Technol Cancer Res Treat 3(6):611–616

    Article  PubMed  Google Scholar 

  21. Harvey JA, Gard CC, Miglioretti DL et al (2013) Reported mammographic density: film-screen versus digital acquisition. Radiology 266(3):752–758

    Article  PubMed  PubMed Central  Google Scholar 

  22. Tagliafico AS, Tagliafico G, Cavagnetto F, Calabrese M, Houssami N (2013) Estimation of percentage breast tissue density: comparison between digital mammography (2D full field digital mammography) and digital breast tomosynthesis according to different BI-RADS categories. Br J Radiol 86(1031):20130255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Moshina N, Roman M, Sebuodegard S, Waade GG, Ursin G, Hofvind S (2018) Comparison of subjective and fully automated methods for measuring mammographic density. Acta Radiol 59(2):154–160

    Article  PubMed  Google Scholar 

  24. Olsen AH, Bihrmann K, Jensen MB, Vejborg I, Lynge E (2009) Breast density and outcome of mammography screening: a cohort study. Br J Cancer 100(7):1205–1208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hodge R, Hellmann SS, von Euler-Chelpin M, Vejborg I, Andersen ZJ (2014) Comparison of Danish dichotomous and BI-RADS classifications of mammographic density. Acta Radiol Short Rep. 3(5):2047981614536558

    PubMed  PubMed Central  Google Scholar 

  26. van der Waal D, den Heeten GJ, Pijnappel RM et al (2015) Comparing visually assessed BI-RADS breast density and automated volumetric breast density software: a cross-sectional study in a breast cancer screening setting. PLoS ONE 10(9):e0136667

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Ji Y, Shao ZZ, Liu JJ, Hao YJ, Liu PF (2018) The correlation between mammographic densities and molecular pathology in breast cancer. Cancer Biomark 22(3):523–531

    Article  CAS  PubMed  Google Scholar 

  28. Masroor I, Rasool M, Saeed SA, Sohail S (2016) To asses inter- and intra-observer variability for breast density and BIRADS assessment categories in mammographic reporting. J Pak Med Assoc 66(2):194–197

    PubMed  Google Scholar 

  29. Ang T, Harkness EF, Maxwell AJ, et al (2017) Visual assessment of breast density using Visual Analogue Scales: observer variability, reader attributes and reading time. Medical Imaging 2017: Image Perception, Observer Performance, and Technology Assessment; 2017: International Society for Optics and Photonics, p. 1013608

  30. Checka CM, Chun JE, Schnabel FR, Lee J, Toth H (2012) The relationship of mammographic density and age: implications for breast cancer screening. AJR Am J Roentgenol 198(3):W292–W295

    Article  PubMed  Google Scholar 

  31. Tseng M, Byrne C (2011) Adiposity, adult weight gain, and mammographic breast density in US Chinese women. International journal of cancer Journal international du cancer. 128(2):418–425

    Article  CAS  PubMed  Google Scholar 

  32. Bertrand KA, Tamimi RM, Scott CG et al (2013) Mammographic density and risk of breast cancer by age and tumor characteristics. Breast Cancer Res 15(6):R104

    Article  PubMed  PubMed Central  Google Scholar 

  33. Cil T, Fishell E, Hanna W et al (2009) Mammographic density and the risk of breast cancer recurrence after breast-conserving surgery. Cancer 115(24):5780–5787

    Article  PubMed  Google Scholar 

  34. Habel LA, Capra AM, Achacoso NS et al (2010) Mammographic density and risk of second breast cancer after ductal carcinoma in situ. Cancer Epidemiol Biomark Prevent 19(10):2488–2495

    Article  Google Scholar 

  35. Boyd NF, Byng JW, Jong RA et al (1995) Quantitative classification of mammographic densities and breast cancer risk: results from the Canadian National Breast Screening Study. J Natl Cancer Inst 87(9):670–675

    Article  CAS  PubMed  Google Scholar 

  36. Boyd NF, Jensen HM, Cooke G, Han HL (1992) Relationship between mammographic and histological risk factors for breast cancer. J Natl Cancer Inst 84(15):1170–1179

    Article  CAS  PubMed  Google Scholar 

  37. Boyd NF, Jensen HM, Cooke G, Han HL, Lockwood GA, Miller AB (2000) Mammographic densities and the prevalence and incidence of histological types of benign breast disease. Reference Pathologists of the Canadian National Breast Screening Study. Eur J Cancer Prev 9(1):15–24

    Article  CAS  PubMed  Google Scholar 

  38. Yaghjyan L, Colditz GA, Collins LC et al (2011) Mammographic breast density and subsequent risk of breast cancer in postmenopausal women according to tumor characteristics. J Natl Cancer Inst 103(15):1179–1189

    Article  PubMed  PubMed Central  Google Scholar 

  39. Sala E, Solomon L, Warren R et al (2000) Size, node status and grade of breast tumours: association with mammographic parenchymal patterns. Eur Radiol 10(1):157–161

    Article  CAS  PubMed  Google Scholar 

  40. Pollan M, Ascunce N, Ederra M et al (2013) Mammographic density and risk of breast cancer according to tumor characteristics and mode of detection: a Spanish population-based case-control study. Breast Cancer Res 15(1):R9

    Article  PubMed  PubMed Central  Google Scholar 

  41. Ko H, Shin J, Lee JE et al (2017) Comparison of the association of mammographic density and clinical factors with ductal carcinoma in situ versus invasive ductal breast cancer in Korean women. BMC cancer. 17(1):821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Gill JK, Maskarinec G, Pagano I, Kolonel LN (2006) The association of mammographic density with ductal carcinoma in situ of the breast: the Multiethnic Cohort. Breast Cancer Res 8(3):R30

    Article  PubMed  PubMed Central  Google Scholar 

  43. Britt K, Ingman W, Huo C, Chew G, Thompson E (2014) The pathobiology of mammographic density. Journal of Cancer Biology & Research. 2(1):1021

    Google Scholar 

  44. Fasching PA, Heusinger K, Loehberg CR et al (2006) Influence of mammographic density on the diagnostic accuracy of tumor size assessment and association with breast cancer tumor characteristics. Eur J Radiol 60(3):398–404

    Article  PubMed  Google Scholar 

  45. Arora N, King TA, Jacks LM et al (2010) Impact of breast density on the presenting features of malignancy. Ann Surg Oncol 17(3):211–218

    Article  PubMed  Google Scholar 

  46. Krishnan K, Baglietto L, Stone J et al (2017) Mammographic density and risk of breast cancer by tumor characteristics: a case-control study. BMC cancer. 17(1):859

    Article  PubMed  PubMed Central  Google Scholar 

  47. Shaikh AJ, Mullooly M, Sayed S et al (2018) Mammographic breast density and breast cancer molecular subtypes: the Kenyan-African aspect. Biomed Res Int. https://doi.org/10.1155/2018/6026315

    Article  PubMed  PubMed Central  Google Scholar 

  48. Maskarinec G, Dartois L, Delaloge S, Hopper J, Clavel-Chapelon F, Baglietto L (2017) Tumor characteristics and family history in relation to mammographic density and breast cancer: the French E3N cohort. Cancer Epidemiol 49(101508793):156–160

    Article  PubMed  Google Scholar 

  49. Aiello EJ, Buist DSM, White E, Porter PL (2005) Association between mammographic breast density and breast cancer tumor characteristics. Cancer Epidemiol BiomarkPrev 14(3):662–668

    Article  Google Scholar 

  50. Eriksson L, Czene K, Rosenberg L, Humphreys K, Hall P (2012) The influence of mammographic density on breast tumor characteristics. Breast Cancer Res Treat 134(2):859–866

    Article  PubMed  Google Scholar 

  51. Ghosh K, Brandt KR, Sellers TA et al (2008) Association of mammographic density with the pathology of subsequent breast cancer among postmenopausal women. Cancer Epidemiol Biomark Prev 17(4):872–879

    Article  Google Scholar 

  52. Masarwah A, Auvinen P, Sudah M et al (2015) Very low mammographic breast density predicts poorer outcome in patients with invasive breast cancer. Eur Radiol 25(7):1875–1882

    Article  PubMed  Google Scholar 

  53. Hawes D, Downey S, Pearce CL et al (2006) Dense breast stromal tissue shows greatly increased concentration of breast epithelium but no increase in its proliferative activity. Breast Cancer Res 8(2):R24

    Article  PubMed  PubMed Central  Google Scholar 

  54. Guo YP, Martin LJ, Hanna W et al (2001) Growth factors and stromal matrix proteins associated with mammographic densities. Cancer Epidemiol Biomark Prev 10(3):243–248

    CAS  Google Scholar 

  55. Huo CW, Huang D, Chew GL et al (2016) Human glandular organoid formation in murine engineering chambers after collagenase digestion and flow cytometry isolation of normal human breast tissue single cells. Cell Biol Int 40(11):1212–1223

    Article  CAS  PubMed  Google Scholar 

  56. Ghosh K, Brandt KR, Reynolds C et al (2012) Tissue composition of mammographically dense and non-dense breast tissue. Breast Cancer Res Treat 131(1):267–275

    Article  PubMed  Google Scholar 

  57. Pinto Pereira SM, McCormack VA, Hipwell JH et al (2011) Localized fibroglandular tissue as a predictor of future tumor location within the breast. Cancer Epidemiol Biomark Prev 20(8):1718–1725

    Article  Google Scholar 

  58. Ursin G, Hovanessian-Larsen L, Parisky YR, Pike MC, Wu AH (2005) Greatly increased occurrence of breast cancers in areas of mammographically dense tissue. Breast Cancer Res 7(5):R605–R608

    Article  PubMed  PubMed Central  Google Scholar 

  59. Vachon CM, Brandt KR, Ghosh K et al (2007) Mammographic breast density as a general marker of breast cancer risk. Cancer Epidemiol Biomark Prev 16(1):43–49

    Article  Google Scholar 

  60. Chan S, Chen J-H, Li S et al (2017) Evaluation of the association between quantitative mammographic density and breast cancer occurred in different quadrants. BMC Cancer 17(1):274

    Article  PubMed  PubMed Central  Google Scholar 

  61. Boyd NF, Dite GS, Stone J et al (2002) Heritability of mammographic density, a risk factor for breast cancer. N Engl J Med 347(12):886–894

    Article  PubMed  Google Scholar 

  62. Brand JS, Humphreys K, Li J, Karlsson R, Hall P, Czene K (2018) Common genetic variation and novel loci associated with volumetric mammographic density. Breast Cancer Res 20(1):30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Boyd NF, Lockwood GA, Byng JW, Tritchler DL, Yaffe MJ (1998) Mammographic densities and breast cancer risk. Cancer Epidemiol Biomark Prev 7(12):1133–1144

    CAS  Google Scholar 

  64. 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 

  65. Bhoo-Pathy N, Verkooijen HM, Tan E-Y et al (2015) Trends in presentation, management and survival of patients with de novo metastatic breast cancer in a Southeast Asian setting. Sci Rep 5:16252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Bozcuk H, Uslu G, Pestereli E et al (2001) Predictors of distant metastasis at presentation in breast cancer: a study also evaluating associations among common biological indicators. Breast Cancer Res Treat 68(3):239–248

    Article  CAS  PubMed  Google Scholar 

  67. Carter CL, Allen C, Henson DE (1989) Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer 63(1):181–187

    Article  CAS  PubMed  Google Scholar 

  68. Huo CW, Waltham M, Khoo C et al (2016) Mammographically dense human breast tissue stimulates MCF10DCIS.com progression to invasive lesions and metastasis. Breast Cancer Res 18(1):106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Eriksson L, Czene K, Rosenberg L, Humphreys K, Hall P (2013) Possible influence of mammographic density on local and locoregional recurrence of breast cancer. Breast Cancer Res 15(4):R56

    Article  PubMed  PubMed Central  Google Scholar 

  70. Huang YS, Chen JLY, Huang CS et al (2016) High mammographic breast density predicts locoregional recurrence after modified radical mastectomy for invasive breast cancer: a case-control study. Breast Cancer Res 18:120

    Article  PubMed  PubMed Central  Google Scholar 

  71. Park CC, Rembert J, Chew K, Moore D, Kerlikowske K (2009) High mammographic breast density is independent predictor of local but not distant recurrence after lumpectomy and radiotherapy for invasive breast cancer. Int J Radiat Oncol Biol Phys 73(1):75–79

    Article  PubMed  Google Scholar 

  72. Bae MS, Moon HG, Han W et al (2016) Early stage triple-negative breast cancer: imaging and clinical-pathologic factors associated with recurrence. Radiology 278(2):356–364

    Article  PubMed  Google Scholar 

  73. Buist DS, Abraham LA, Barlow WE et al (2010) Diagnosis of second breast cancer events after initial diagnosis of early stage breast cancer. Breast Cancer Res Treat 124(3):863–873

    Article  PubMed  PubMed Central  Google Scholar 

  74. Strand F, Humphreys K, Holm J et al (2018) Long-term prognostic implications of risk factors associated with tumor size: a case study of women regularly attending screening. Breast Cancer Res 20(1):31

    Article  PubMed  PubMed Central  Google Scholar 

  75. Raviraj V, Fok S, Zhao J et al (2012) Regulation of ROCK1 via Notch1 during breast cancer cell migration into dense matrices. BMC Cell Biol 13:12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Boyd NF, Melnichouk O, Martin LJ et al (2011) Mammographic density, response to hormones, and breast cancer risk. J Clin Oncol 29(22):2985–2992

    Article  CAS  PubMed  Google Scholar 

  77. Sprague BL, Trentham-Dietz A, Gangnon RE et al (2011) Circulating sex hormones and mammographic breast density among postmenopausal women. Horm Cancer 2(1):62–72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Conroy SM, Pagano I, Kolonel LN, Maskarinec G (2011) Mammographic density and hormone receptor expression in breast cancer: the Multiethnic Cohort Study. Cancer Epidemiol 35(5):448–452

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Ding J, Warren R, Girling A, Thompson D, Easton D (2010) Mammographic density, estrogen receptor status and other breast cancer tumor characteristics. Breast J 16(3):279–289

    Article  PubMed  Google Scholar 

  80. Hinton CP, Roebuck EJ, Williams MR et al (1985) Mammographic parenchymal patterns—value as a predictor of hormone dependency and survival in breast-canceR. Am J Roentgenol 144(6):1103–1107

    Article  CAS  Google Scholar 

  81. Kim MY, Choi N, Yang JH, Yoo YB, Park KS (2015) Background parenchymal enhancement on breast MRI and mammographic breast density: correlation with tumour characteristics. Clin Radiol 70(7):706–710

    Article  CAS  PubMed  Google Scholar 

  82. Heusinger K, Jud SM, Haberle L et al (2012) Association of mammographic density with hormone receptors in invasive breast cancers: results from a case-only study. Int J Cancer 131(11):2643–2649

    Article  CAS  PubMed  Google Scholar 

  83. Roubidoux MA, Bailey JE, Wray LA, Helvie MA (2004) Invasive cancers detected after breast cancer screening yielded a negative result: relationship of mammographic density to tumor prognostic factors. Radiology 230(1):42–48

    Article  PubMed  Google Scholar 

  84. Nielsen NS, Andersen J, Poulsen HS, Mathiessen O (1992) Prediction of hormone responsiveness by mammographic parenchymal pattern in advanced primary breast cancer. Breast Cancer Res Treat 23(3):219–222

    Article  CAS  PubMed  Google Scholar 

  85. Verheus M, Maskarinec G, Erber E et al (2009) Mammographic density and epithelial histopathologic markers. BMC Cancer 9:182

    Article  PubMed  PubMed Central  Google Scholar 

  86. Shaaban AM, O’Neill PA, Davies MP et al (2003) Declining estrogen receptor-beta expression defines malignant progression of human breast neoplasia. Am J Surg Pathol 27(12):1502–1512

    Article  PubMed  Google Scholar 

  87. Nelson AW, Groen AJ, Miller JL et al (2017) Comprehensive assessment of estrogen receptor beta antibodies in cancer cell line models and tissue reveals critical limitations in reagent specificity. Mol Cell Endocrinol 440:138–150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Hwang K-T, Chu AJ, Kim J et al (2018) Prognostic influence of preoperative mammographic breast density in operable invasive female breast cancer. Sci Rep 8(1):16075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Edwards BL, Atkins KA, Stukenborg GJ et al (2017) The association of mammographic density and molecular breast cancer subtype. Cancer Epidemiol Biomark Prev 26(10):1487–1492

    Article  Google Scholar 

  90. Krishnan K, Baglietto L, Stone J et al (2017) Longitudinal study of mammographic density measures that predict breast cancer risk. Cancer Epidemiol Biomark Prev 26(4):651–660

    Article  Google Scholar 

  91. Brisson J, Morrison AS, Khalid N (1988) Mammographic parenchymal features and breast-cancer in the breast-cancer detection demonstration project. J Natl Cancer Inst 80(19):1534–1540

    Article  CAS  PubMed  Google Scholar 

  92. Gilliland FD, Joste N, Stauber PM et al (2000) Biologic characteristics of interval and screen-detected breast cancers. J Natl Cancer Inst 92(9):743–749

    Article  CAS  PubMed  Google Scholar 

  93. Strand F, Humphreys K, Eriksson M et al (2017) Longitudinal fluctuation in mammographic percent density differentiates between interval and screen-detected breast cancer. Int J Cancer 140(1):34–40

    Article  CAS  PubMed  Google Scholar 

  94. Nickson C, Arzhaeva Y, Aitken Z et al (2013) AutoDensity: an automated method to measure mammographic breast density that predicts breast cancer risk and screening outcomes. Breast Cancer Res 15(5):R80

    Article  PubMed  PubMed Central  Google Scholar 

  95. Olsson Å, Sartor H, Borgquist S, Zackrisson S, Manjer J (2014) Breast density and mode of detection in relation to breast cancer specific survival: a cohort study. BMC Cancer 14:229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. van der Waal D, Verbeek ALM, Broeders MJM (2018) Breast density and breast cancer-specific survival by detection mode. BMC Cancer 18(1):386

    Article  PubMed  PubMed Central  Google Scholar 

  97. Holm J, Humphreys K, Li J et al (2015) Risk factors and tumor characteristics of interval cancers by mammographic density. J Clin Oncol 33(9):1030–1037

    Article  PubMed  Google Scholar 

  98. Kamineni A, Anderson ML, White E et al (2013) Body mass index, tumor characteristics, and prognosis following diagnosis of early-stage breast cancer in a mammographically screened population. Cancer Causes Control 24(2):305–312

    Article  PubMed  Google Scholar 

  99. Eriksson L, Czene K, Rosenberg LU, Tornberg S, Humphreys K, Hall P (2013) Mammographic density and survival in interval breast cancers. Breast Cancer Res 15(3):R48

    Article  PubMed  PubMed Central  Google Scholar 

  100. Elsamany S, Alzahrani A, Abozeed WN et al (2015) Mammographic breast density: predictive value for pathological response to neoadjuvant chemotherapy in breast cancer patients. Breast 24(5):576–581

    Article  CAS  PubMed  Google Scholar 

  101. Li J, Humphreys K, Eriksson L, Edgren G, Czene K, Hall P (2013) Mammographic density reduction is a prognostic marker of response to adjuvant tamoxifen therapy in postmenopausal patients with breast cancer. J Clin Oncol 31(18):2249–2256

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Nyante SJ, Sherman ME, Pfeiffer RM et al (2015) Prognostic significance of mammographic density change after initiation of tamoxifen for ER-positive breast cancer. J Natl Cancer Inst 107(3):dju425

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Ko KL, Shin IS, You JY, Jung SY, Ro J, Lee ES (2013) Adjuvant tamoxifen-induced mammographic breast density reduction as a predictor for recurrence in estrogen receptor-positive premenopausal breast cancer patients. Breast Cancer Res Treat 142(3):559–567

    Article  CAS  PubMed  Google Scholar 

  104. Kim J, Han W, Moon HG et al (2012) Breast density change as a predictive surrogate for response to adjuvant endocrine therapy in hormone receptor positive breast cancer. Breast Cancer Res 14(4):R102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Redfern A, Martin H, Stone J, Davidson J, Yap F, Chung K (2016) Mammographic breast density as a predictor of hormone receptor positive breast cancer recurrence: a single centre longitudinal analysis. Can Res 76(4 Supplement):PD1-06-PD1

    Google Scholar 

  106. Sandberg MEC, Li J, Hall P et al (2013) Change of mammographic density predicts the risk of contralateral breast cancer–a case-control study. Breast Cancer Res 15(4):R57

    Article  PubMed  PubMed Central  Google Scholar 

  107. Chowdhury M, Euhus D, Onega T, Biswas S, Choudhary PK (2017) A model for individualized risk prediction of contralateral breast cancer. Breast Cancer Res Treat 161(1):153–160

    Article  CAS  PubMed  Google Scholar 

  108. Hwang ES, Miglioretti DL, Ballard-Barbash R, Weaver DL, Kerlikowske K (2007) Association between breast density and subsequent breast cancer following treatment for ductal carcinoma in situ. Cancer Epidemiol Biomark Prev 16(12):2587–2593

    Article  Google Scholar 

  109. Chowdhury M, Euhus D, O’Donnell M, Onega T, Choudhary PK, Biswas S (2018) Dose-dependent effect of mammographic breast density on the risk of contralateral breast cancer. Breast Cancer Res Treat 170(1):143–148

    Article  PubMed  PubMed Central  Google Scholar 

  110. Knight JA, Blackmore KM, Fan J et al (2018) The association of mammographic density with risk of contralateral breast cancer and change in density with treatment in the WECARE study. Breast Cancer Res 20(1):23

    Article  PubMed  PubMed Central  Google Scholar 

  111. Raghavendra A, Sinha AK, Le-Petross HT et al (2017) Mammographic breast density is associated with the development of contralateral breast cancer. Cancer 123(11):1935–1940

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Maskarinec G, Pagano IS, Little MA, Conroy SM, Park SY, Kolonel LN (2013) Mammographic density as a predictor of breast cancer survival: the Multiethnic Cohort. Breast Cancer Res 15(1):R7

    Article  PubMed  PubMed Central  Google Scholar 

  113. Habel LA, Dignam JJ, Land SR, Salane M, Capra AM, Julian TB (2004) Mammographic density and breast cancer after ductal carcinoma in situ. J Natl Cancer Inst 96(19):1467–1472

    Article  PubMed  PubMed Central  Google Scholar 

  114. Barcellos-Hoff MH, Medina D (2005) New highlights on stroma-epithelial interactions in breast cancer. Breast Cancer Res 7(1):33–36

    Article  CAS  PubMed  Google Scholar 

  115. Ziv E, Shepherd J, Smith-Bindman R, Kerlikowske K (2003) Mammographic breast density and family history of breast cancer. J Natl Cancer Inst 95(7):556–558

    Article  PubMed  Google Scholar 

  116. Andersson TML, Crowther MJ, Czene K, Hall P, Humphreys K (2017) Mammographic density reduction as a prognostic marker for postmenopausal breast cancer: results using a joint longitudinal-survival modeling approach. Am J Epidemiol 186(9):1065–1073

    Article  PubMed  PubMed Central  Google Scholar 

  117. Gierach GL, Ichikawa L, Kerlikowske K et al (2012) Relationship between mammographic density and breast cancer death in the Breast Cancer Surveillance Consortium. J Natl Cancer Inst 104(16):1218–1227

    Article  PubMed  PubMed Central  Google Scholar 

  118. Porter GJR, Evans AJ, Cornford EJ et al (2007) Influence of mammographic parenchymal pattern in screening-detected and interval invasive breast cancers on pathologic features, mammographic features, and patient survival. Am J Roentgenol 188(3):676–683

    Article  Google Scholar 

  119. Chiu SY, Duffy S, Yen AM, Tabar L, Smith RA, Chen HH (2010) Effect of baseline breast density on breast cancer incidence, stage, mortality, and screening parameters: 25-year follow-up of a Swedish mammographic screening. Cancer Epidemiol Biomark Prev 19(5):1219–1228

    Article  Google Scholar 

  120. Zhang S, Ivy JS, Diehl KM, Yankaskas BC (2013) The association of breast density with breast cancer mortality in African American and white women screened in community practice. Breast Cancer Res Treat 137(1):273–283

    Article  PubMed  Google Scholar 

  121. Elsamany S, Alzahrani A, Elkhalik SA et al (2014) Prognostic value of mammographic breast density in patients with metastatic breast cancer. Med Oncol 31(8):96

    Article  PubMed  Google Scholar 

  122. Radenkovic S, Konjevic G, Gavrilovic D et al (2018) pSTAT3 expression associated with survival and mammographic density of breast cancer patients. Pathol Res Pract 215:366–372

    Article  CAS  PubMed  Google Scholar 

  123. Raviraj V, Zhang H, Chien HY, Cole L, Thompson EW, Soon L (2012) Dormant but migratory tumour cells in desmoplastic stroma of invasive ductal carcinomas. Clin Exp Metastasis 29(3):273–292

    Article  PubMed  Google Scholar 

  124. Redfern AD, Spalding LJ, Thompson EW (2018) The Kraken Wakes: induced EMT as a driver of tumour aggression and poor outcome. Clin Exp Metastasis 35(4):285–308

    Article  PubMed  Google Scholar 

  125. Vachon CM, Suman VJ, Brandt KR et al (2013) Mammographic breast density response to aromatase inhibition. Clin Cancer Res 19(8):2144–2153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Boyd NF, Osullivan B, Campbell JE et al (1982) Mammographic patterns and bias in breast-cancer detection. Radiology 143(3):671–674

    Article  CAS  PubMed  Google Scholar 

  127. Sala E, Warren R, McCann J, Duffy S, Luben R, Day N (2001) Mammographic parenchymal patterns and breast cancer natural history–a case-control study. Acta Oncol 40(4):461–465

    Article  CAS  PubMed  Google Scholar 

  128. Morishita M, Ohtsuru A, Hayashi T et al (2005) Clinical significance of categorisation of mammographic density for breast cancer prognosis. Int J Oncol 26(5):1307–1312

    PubMed  Google Scholar 

  129. Garnett S, Wallis M, Morgan G (2009) Do screen-detected lobular and ductal carcinoma present with different mammographic features? Br J Radiol 82(973):20–27

    Article  CAS  PubMed  Google Scholar 

  130. Nickson C, Kavanagh AM (2009) Tumour size at detection according to different measures of mammographic breast density. J Med Screen 16(3):140–146

    Article  PubMed  Google Scholar 

  131. Pinker K, Perry N, Vinnicombe S, Shiel S, Weber M (2011) Conspicuity of breast cancer according to histopathological type and breast density when imaged by full-field digital mammography compared with screen-film mammography. Eur Radiol 21(1):18–25

    Article  PubMed  Google Scholar 

  132. Eriksson L, Hall P, Czene K et al (2012) Mammographic density and molecular subtypes of breast cancer. Br J Cancer 107(1):18–23

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Moshina N, Ursin G, Hoff SR et al (2015) Mammographic density and histopathologic characteristics of screen-detected tumors in the Norwegian Breast Cancer Screening Program. Acta Radiol Open 4(9):2058460115604340

    PubMed  PubMed Central  Google Scholar 

  134. Ciatto S, Cecchini S, Iossa A et al (1989) Association of estrogen receptors with parenchymal pattern at mammography. Radiology 170(3 Pt 1):695–697

    Article  CAS  PubMed  Google Scholar 

  135. Ferranti C, Coopmans de Yoldi G, Biganzoli E et al (2000) Relationships between age, mammographic features and pathological tumour characteristics in non-palpable breast cancer. Br J Radiol 73(871):698–705

    Article  CAS  PubMed  Google Scholar 

  136. Ziv E, Tice J, Smith-Bindman R, Shepherd J, Cummings S, Kerlikowske K (2004) Mammographic density and estrogen receptor status of breast cancer. Cancer Epidemiol Biomark Prev 13(12):2090–2095

    CAS  Google Scholar 

  137. Yang WT, Dryden M, Broglio K et al (2008) Mammographic features of triple receptor-negative primary breast cancers in young premenopausal women. Breast Cancer Res Treat 111(3):405–410

    Article  PubMed  Google Scholar 

  138. Kavanagh AM, Byrnes GB, Nickson C et al (2008) Using mammographic density to improve breast cancer screening outcomes. Cancer Epidemiol Biomark Prev 17(10):2818–2824

    Article  Google Scholar 

  139. Ma H, Luo J, Press MF, Wang Y, Bernstein L, Ursin G (2009) Is there a difference in the association between percent mammographic density and subtypes of breast cancer? Luminal A and triple-negative breast cancer. Cancer Epidemiol Biomark Prev 18(2):479–485

    Article  CAS  Google Scholar 

  140. Jiang LY, Ma TT, Moran MS et al (2011) Mammographic Features Are Associated with Clinicopathological Characteristics in Invasive Breast Cancer. Anticancer Res 31(6):2327–2334

    CAS  PubMed  Google Scholar 

  141. Phipps AI, Buist DSM, Malone KE et al (2012) Breast density, body mass index, and risk of tumor marker-defined subtypes of breast cancer. Ann Epidemiol 22(5):340–348

    Article  PubMed  PubMed Central  Google Scholar 

  142. Razzaghi H, Troester MA, Gierach GL, Olshan AF, Yankaskas BC, Millikan RC (2013) Association between mammographic density and basal-like and luminal A breast cancer subtypes. Breast Cancer Res 15(5):R76

    Article  PubMed  PubMed Central  Google Scholar 

  143. Kim MY, Choi N (2013) Mammographic and ultrasonographic features of triple-negative breast cancer: a comparison with other breast cancer subtypes. Acta Radiol 54(8):889–894

    Article  PubMed  Google Scholar 

  144. Rauch GM, Kuerer HM, Scoggins ME et al (2013) Clinicopathologic, mammographic, and sonographic features in 1,187 patients with pure ductal carcinoma in situ of the breast by estrogen receptor status. Breast Cancer Res Treat 139(3):639–647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Gao B, Zhang H, Zhang SD et al (2014) Mammographic and clinicopathological features of triple-negative breast cancer. Br J Radiol 87(1039):20130496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Yaghjyan L, Pettersson A, Colditz GA et al (2015) Postmenopausal mammographic breast density and subsequent breast cancer risk according to selected tissue markers. Br J Cancer 113(7):1104–1113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Sartor H, Zackrisson S, Elebro K, Hartman L, Borgquist S (2015) Mammographic density in relation to tumor biomarkers, molecular subtypes, and mode of detection in breast cancer. Cancer Causes Control 26(6):931–939

    Article  PubMed  Google Scholar 

  148. Kim MY, Kim HS, Choi N, Yang JH, Yoo YB, Park KS (2015) Screening mammography-detected ductal carcinoma in situ: mammographic features based on breast cancer subtypes. Clin Imaging 39(6):983–986

    Article  PubMed  Google Scholar 

  149. Jung HK, Han K, Lee YJ, Moon HJ, Kim E-K, Kim MJ (2015) Mammographic and sonographic features of triple-negative invasive carcinoma of no special type. Ultrasound Med Biol 41(2):375–383

    Article  PubMed  Google Scholar 

  150. Shin J, Lee JE, Ko HY et al (2018) Association between mammographic density and tumor marker-defined breast cancer subtypes: a case-control study. Eur J Cancer Prev 27(3):239–247

    CAS  PubMed  Google Scholar 

  151. van Gils CH, Otten JDM, Hendriks J, Holland R, Straatman H, Verbeek ALM (1999) High mammographic breast density and its implications for the early detection of breast cancer. J Med Screen 6(4):200–204

    Article  PubMed  Google Scholar 

  152. Mandelson MT, Oestreicher N, Porter PL et al (2000) Breast density as a predictor of mammographic detection: comparison of interval- and screen-detected cancers. J Natl Cancer Inst 92(13):1081–1087

    Article  CAS  PubMed  Google Scholar 

  153. Crane CEB, Luke CG, Rogers JM, Playford PE, Roder DM (2002) An analysis of factors associated with interval as opposed to screen-detected breast cancers, including hormone therapy and mammographic density. Breast 11(2):131–136

    Article  CAS  PubMed  Google Scholar 

  154. Ciatto S, Visioli C, Paci E, Zappa M (2004) Breast density as a determinant of interval cancer at mammographic screening. Br J Cancer 90(2):393–396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Chiarelli AM, Kirsh VA, Klar NS et al (2006) Influence of patterns of hormone replacement therapy use and mammographic density on breast cancer detection. Cancer Epidemiol Biomark Prev 15(10):1856–1862

    Article  CAS  Google Scholar 

  156. Domingo L, Salas D, Zubizarreta R et al (2014) Tumor phenotype and breast density in distinct categories of interval cancer: results of population-based mammography screening in Spain. Breast Cancer Res 16(1):R3

    Article  PubMed  PubMed Central  Google Scholar 

  157. Chiarelli AM, Prummel MV, Muradali D et al (2015) Digital versus screen-film mammography: impact of mammographic density and hormone therapy on breast cancer detection. Breast Cancer Res Treat 154(2):377–387

    Article  PubMed  Google Scholar 

  158. Strand F, Humphreys K, Cheddad A et al (2016) Novel mammographic image features differentiate between interval and screen-detected breast cancer: a case-case study. Breast Cancer Res 18:100

    Article  PubMed  PubMed Central  Google Scholar 

  159. Timmermans L, Bleyen L, Bacher K et al (2017) Screen-detected versus interval cancers: effect of imaging modality and breast density in the Flemish Breast Cancer Screening Programme. Eur Radiol 27(9):3810–3819

    Article  PubMed  Google Scholar 

  160. Nguyen TL, Aung YK, Li S et al (2018) Predicting interval and screen-detected breast cancers from mammographic density defined by different brightness thresholds. Breast Cancer Res 20:152

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The Translational Research Institute receives funding from the Australian Government. Author M.S.S. would like to thank the Ministry of Higher Education-Missions sector, Egypt, and the British Council for their support through Newton–Mosharafa programme via the Egyptian Cultural Bureau in London.

Funding

The authors have received research grants from the University of Melbourne and St Vincent’s Hospital Melbourne Foundation, Melbourne, Australia; the Translational Research Institute and Princess Alexandra Research Foundation, Brisbane, Australia; however, none have any financial relationship with these organisations.

Author information

Author notes

  1. Michael S Shawky and Cecilia W Huo: co-first authors with equal contribution.

  2. Kara Britt and Erik W Thompson: co-senior authors with equal contribution.

Authors and Affiliations

  1. Department of Head and Neck and Endocrine Surgery, Faculty of Medicine, University of Alexandria, Alexandria, Egypt

    Michael S. Shawky

  2. Department of Breast Surgery, St Bartholomew Hospital (Barts), London, UK

    Michael S. Shawky

  3. Department of Surgery, St Vincent’s Hospital, University of Melbourne, Melbourne, VIC, Australia

    Cecilia W. Huo, Michael A. Henderson & Erik W. Thompson

  4. Sir Peter MacCallum Department of Oncology, University of Melbourne, Grattan Street, Parkville, Melbourne, VIC, 3010, Australia

    Kara Britt

  5. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

    Michael A. Henderson & Kara Britt

  6. School of Medicine, University of Western Australia, Perth, WA, Australia

    Andrew Redfern

  7. Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia

    Erik W. Thompson

  8. Translational Research Institute, Rm 7031, 37 Kent St., Woolloongabba, Brisbane, QLD, Australia

    Erik W. Thompson

Authors
  1. Michael S. Shawky
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cecilia W. Huo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael A. Henderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Andrew Redfern
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kara Britt
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Erik W. Thompson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Erik W. Thompson.

Ethics declarations

Conflict of interest

Author Redfern is on Advisory Boards for Novartis, Roche, Eisai and Pfizer, but has no shares or other investments. Author Thompson has received consultancy fees from Eisai for a different topic but has no shares or other investments. None of these companies stand to benefit directly or indirectly from this paper. All authors declare that they have no conflict of interest.

Ethical approval/informed consent

This is a review article that does not contain any studies with human participants or animals performed by any of the authors.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shawky, M.S., Huo, C.W., Henderson, M.A. et al. A review of the influence of mammographic density on breast cancer clinical and pathological phenotype. Breast Cancer Res Treat 177, 251–276 (2019). https://doi.org/10.1007/s10549-019-05300-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-019-05300-1

Keywords

Search

Navigation