Mammographic density and factors determining it from the point of view of high oncological risks

There is now extensive proof that high percentage of mammographic density (MD) is an independent risk factor for breast cance.r Taking this into account, the research data are summarized with regard to relation of MD to anthropometric, as well as hormonal, genetic and genotoxic factors. There is a negative correlation between MD and such risk factors as age, number of deliveries, BMI and waist-hip ratio. Most inves- tigations show a direct connection between MD and prolactin level or insulin-like growth factor in blood, mostly in premenopaus al women. Relations of MD with blood estrogens, testosterone, sex hormone binding globulin prove to be too diverse to be taken in account of. It is pos- sible that the action of hormones, especially estrogens, is mediated through their metabolites catecholestrogens and / or reactive oxygen spe- cies. There is certain evidence that a genetic component plays a role in MD. It refers to COMT Val158Met, IGF-I rs6220 A> G and UGT1A1 in premenopausal women, and to ESR1 (XbaI и PvuII) in menopausal cases.
Although it is obvious that the risk of breast cancer related to MD is brought about by many factors, there is a necessity for studying addi- tional criteria modifying the process, as well as for searching means for preventing it.

1. Чиссов В.И., Старинский В.В., Петрова Г.В. Злокачественные новообразования в России в 2007 году (заболеваемость и смертность). М.: МНИОИ им. П.А. Герцена, 2009.

2. Ginsburg O.M., Martin L.J., Boyd N.F. Mammographic density, lobular involution, and risk of breast cancer. Br J Cancer 2008;99(9):1369–74.

3. Li T., Sun L., Miller N. et al. The association of measured breast tissue characteristics with mammographic density and other risk factors for breast cancer. Cancer Epidemiol Biomark Prev 2005;14(2):343–9.

4. Boyd N.F., Guo H., Martin L.J. et al. Mammographic density and the risk and detection of breast cancer. N Engl J Med 2007;356(3):227–36.

5. Martin L.J., Boyd N.F. Mammographic density. Potential mechanisms of breast cancer risk associated with mammographic density: hypotheses based on epidemiological evidence. Breast Cancer Res 2008;10(1):201.

6. Maskarinec G., Pagano I., Lurie G., Kolonel L.N. A longitudinal investigation of mammographic density: the multiethnic cohort. Cancer Epidemiol Biomark Prev 2006;15(4):732–9.

7. Васильев Д.А., Семенова Н.В., Берштейн Л.М. Сахарный диабет, нарушение толерантности к глюкозе и злокачественные образования: степень риска и меры воздействия. Рос онкол журн 2008;(3):49–54.

8. Семиглазов В.Ф., Семиглазов В.В., Клецель А.Е. Неинвазивные и инвазивные опухоли молочной железы. СПб., 2006.

9. Vachon C.M., Sellers T.A., Vierkant R.A. et al. Case-control study of increased mammographic breast density response to hormone replacement therapy. Cancer Epidemiol Biomark Prev 2002;11(11):1382–8.

10. McCormack V.A., dos Santos Silva I. Breast density and parenchymal patterns as markers of breast cancer risk: a meta- analysis. Cancer Epidemiol Biomark Prev 2006;15(6):1159–69.

11. Santen R.J., Boyd N.F., Chlebowski R.T. et al. Critical assessment of new risk factors for breast cancer: considerations for development of an improved risk prediction model. Endocr Relat Cancer 2007;14(2):169–87.

12. Pike M.C., Krailo M.D., Henderson B.E. et al. “Hormonal” risk factors, “breast tissue age” and the age-incidence of breast cancer. Nature 1983;303(5920):767–70.

13. Diorio C., Pollak M., Byrne C. et al. Levels of C-peptide and mammographic breast density. Cancer Epidemiol Biomark Prev 2005;14:2661–4.

14. Furberg A.S., Jasienska G., Bjurstam N. et al. Metabolic and hormonal profiles: HDL cholesterol as a plausible biomarker of breast cancer risk. The Norwegian EBBA Study. Cancer Epidemiol Biomark Prev 2005;14(1):33–40.

15. Maskarinec G., Woolcott C., Steude J.S. et al. The relation of leptin and adiponectin with breast density among premenopausal women. Eur J Cancer Prev 2010;19(1):55–60.

16. Reeves K.W., Stone R.A., Modugno F. et al. Longitudinal association of anthropometry with mammographic breast density in the Study of Women's Health Across the Nation. Int J Cancer 2009;124(5):1169–77.

17. de Moura Ramos E.H., Martinelli S., Silva I. et al. Association between estrogen receptor gene polymorphisms and breast density in postmenopausal women. Climacteric 2009;12(6):490–501.

18. Guthrie J.R., Milne R.L., Hopper J.L. et al. Mammographic densities during the menopausal transition: a longitudinal study of Australian-born women. Menopause 2007;14(2):208–15.

19. Tamimi R.M., Byrne C., Colditz G.A., Hankinson S.E. Endogenous hormone levels, mammographic density, and subsequent risk of breast cancer in postmenopausal women. J Natl Cancer Inst 2007;99(15):1178–87.

20. Riza E., Remoundos D.D., Bakali E. et al. Anthropometric characteristics and mammographic parenchymal patterns in post-menopausal women: a population- based study in Northern Greece. Cancer Causes Control 2009;20(2):181–91.

21. Коновалова В.Н. Взаимосвязь состояния молочных желез и гидроксиметаболизма эстрогенов у женщин в постменопаузе на фоне различных режимов заместительной гормонотерапии. Авто- реф. дис. ... канд. мед. наук. М., 2008.

22. Rutter C.M., Mandelson M.T., Laya M.B. et al. Changes in breast density associated with initiation, discontinuation, and continuing use of hormone replacement therapy. Jama 2001;285(2):171–6.

23. Becker S., Kaaks R. Exogenous and endogenous hormones, mammographic density and breast cancer risk: can mammo- graphic density be considered an intermediate marker of risk? Recent Results Cancer Res 2009;181:135–57.

24. Meyer F., Brisson J., Morrison A.S., Brown J.B. Endogenous sex hormones, prolactin, and mammography features of breast tissue in premenopausal women. J Natl Cancer Inst 1986;77(3):617–20.

25. Noh J.J., Maskarinec G., Pagano I. et al. Mammographic densities and circulating hormones: a cross-sectional study in premenopausal women. Breast 2006;15(1):20–8.

26. Bremnes Y., Ursin G., Bjurstam N. et al. Endogenous sex hormones, prolactin and mammographic density in postmenopausal Norwegian women. Int J Cancer 2007;121(11):2506–11.

27. Greendale G.A., Palla S.L., Ursin G. et al. The association of endogenous sex steroids and sex steroid binding proteins with mammographic density: results from the Postmenopausal Estrogen/Progestin Interventions Mammographic Density Study. Am J Epidemiol 2005;162(9):826–34.

28. Aiello E.J., Tworoger S.S., Yasui Y. et al. Associations among circulating sex hormones, insulin-like growth factor, lipids, and mammographic density in postmenopausal women. Cancer Epidemiol Biomark Prev 2005;14(6):1411–7.

29. McCormack V.A., Dowsett M., Folkerd E. et al. Sex steroids, growth factors and mammographic density: a cross- sectional study of UK postmenopausal Caucasian and Afro-Caribbean women. Breast Cancer Res 2009;11(3):38.

30. Sprague B.L., Trentham-Dietz A., Gangnon R.E. et al. Circulating sex hormones and mammographic breast density among postmenopausal women. Horm Cancer 2011;2(1):62–72.

31. Verheus M., Peeters P.H., van Noord P.A. et al. No relationship between circulating levels of sex steroids and mammographic breast density: the Prospect-EPIC cohort. Breast Cancer Res 2007;9(4):53.

32. Warren R., Skinner J., Sala E. et al. Associations among mammographic density, circulating sex hormones, and poly- morphisms in sex hormone metabolism genes in postmenopausal women. Cancer Epidemiol Biomark Prev 2006;15(8):1502–8.

33. Boyd N.F., Stone J., Martin L.J. et al. The association of breast mitogens with mammographic densities. Br J Cancer 2002;87(8):876–82.

34. Yong M., Atkinson C., Newton K.M. et al. Associations between endogenous sex hormone levels and mammographic and bone densities in premenopausal women. Cancer Causes Control 2009;20(7):1039–53.

35. Johansson H., Gandini S., Bonanni B. et al. Relationships between circulating hormone levels, mammographic percent density and breast cancer risk factors in postmenopausal women. Breast Cancer Res Treat 2008;108(1):57–67.

36. Walker K., Fletcher O., Johnson N. et al. Premenopausal mammographic density in relation to cyclic variations in endogenous sex hormone levels, prolactin, and insulin- like growth factors. Cancer Res 2009;69(16):6490–9.

37. Mulhall C., Hegele R.A., Cao H. et al. Pituitary growth hormone and growth hormone-releasing hormone receptor genes and associations with mammographic measures and serum growth hormone. Cancer Epidemiol Biomark Prev 2005;14:2648–54.

38. Maskarinec G., Takata Y., Chen Z. et al. IGF-I and mammographic density in four geographic locations: a pooled analysis. Int J Cancer 2007;121(8):1786–92.

39. Bremnes Y., Ursin G., Bjurstam N. et al. Insulin-like growth factor and mammo- graphic density in postmenopausal Norwegian women. Cancer Epidemiol Biomark Prev 2007;16(1):57–62.

40. Strange K.S., Wilkinson D., Edin G., Emerman J.T. Mitogenic properties of insulin-like growth factors I and II, insulin- like growth factor binding protein-3 and epidermal growth factor on human breast stromal cells in primary culture. Breast Cancer Res Treat 2004;84(2):77–84.

41. Byrne C., Colditz G.A., Willett W.C. et al. Plasma insulin-like growth factor (IGF) I, IGF-binding protein 3, and mammographic density. Cancer Res 2000;60(14):3744–8.

42. Diorio C., Pollak M., Byrne C. et al. Insulin-like growth factor-I, IGF-binding protein-3, and mammographic breast density. Cancer Epidemiol Biomark Prev 2005;14(5):1065–73.

43. Guo Y.P., Martin L.J., Hanna W. et al. Growth factors and stromal matrix proteins associated with mammographic densities. Cancer Epidemiol Biomark Prev 2001;10(3):243–8.

44. dos Santos Silva I., Johnson N., de Stavola B. et al. The insulin-like growth factor system and mammographic features in premenopausal and postmenopausal women. Cancer Epidemiol Biomark Prev 2006;15(3):449–55.

45. Lai J.H., Vesprini D., Zhang W. et al. A polymorphic locus in the promoter region of the IGFBP3 gene is related to mammo- graphic breast density. Cancer Epidemiol Biomark Prev 2004;13(4):573–82.

46. Verheus M., McKay J.D., Kaaks R. et al. Common genetic variation in the IGF-1 gene, serum IGF-I levels and breast density. Breast Cancer Res Treat 2008;112(1):109–22.

47. Verheus M., Peeters P.H., Kaaks R. et al. Premenopausal insulin-like growth factor-I serum levels and changes in breast density over menopause. Cancer Epidemiol Biomark Prev 2007;16(3):451–7.

48. Берштейн Л.М., Васильев Д.А., Коваленко И.Г. и др. Изучение связи маммографической плотности молочных желез с эффектами глюкозы и уровнем циркулирующих в крови стволовых клеток. Вопр онкол 2011;57(1):42–7.

49. Stuedal A., Ursin G., Veierod M.B. et al. Plasma levels of leptin and mammographic density among postmenopausal women: a cross-sectional study. Breast Cancer Res 2006;8(5):55.

50. Crest A.B., Aiello E.J., Anderson M.L., Buist D.S. Varying levels of family history of breast cancer in relation to mammographic breast density (United States). Cancer Causes Control 2006;17(6):843–50.

51. Hong C.C., Thompson H.J., Jiang C. et al. Val158Met polymorphism in catechol- O-methyltransferase gene associated with risk factors for breast cancer. Cancer Epidemiol Biomark Prev 2003;12(9):838–47.

52. Maskarinec G., Lurie G., Williams A.E., Le Marchand L. An investigation of mammographic density and gene variants in healthy women. Int J Cancer 2004;112(4):683–8.

53. Dumas I., Diorio C. Polymorphisms in genes involved in the estrogen pathway and mammographic density. BMC Cancer 2010;10:636.

54. Haiman C.A., Hankinson S.E., De Vivo I. et al. Polymorphisms in steroid hormone pathway genes and mammographic density. Breast Cancer Res Treat 2003;77(1):27–36.

55. van Duijnhoven F.J., Bezemer I.D., Peeters P.H. et al. Polymorphisms in the estrogen receptor alpha gene and mammo- graphic density. Cancer Epidemiol Biomark Prev 2005;14:2655–60.

56. Crandall C.J., Sehl M.E., Crawford S.L. et al. Sex steroid metabolism polymorphisms and mammographic density in pre- and early perimenopausal women. Breast Cancer Res 2009;11(4):51.

57. Haakensen V.D., Biong M., Lingjaerde O.C. et al. Expression levels of uridine 5'-diphospho- glucuronosyltransferase genes in breast tissue from healthy women are associated with mammographic density. Breast Cancer Res 2010;12(4):65.

58. Chambo D., Kemp C., Costa A.M. et al. Polymorphism in CYP17, GSTM1 and the progesterone receptor genes and its relationship with mammographic density. Braz J Med Biol Res 2009;42(4):323–9.

59. Diorio C., Brisson J., Berube S., Pollak M. Genetic polymorphisms involved in insulin-like growth factor (IGF) pathway in relation to mammographic breast density and IGF levels. Cancer Epidemiol Biomarkers Prev 2008;17(4):880–8.

60. Biong M., Gram I.T., Brill I. et al. Genotypes and haplotypes in the insulin-like growth factors, their receptors and binding proteins in relation to plasma metabolic levels and mammographic density. BMC Med Genomics 2010;3(9).

61. Mitchell G., Antoniou A.C., Warren R. et al. Mammographic density and breast cancer risk in BRCA1 and BRCA2 mutation carriers. Cancer Res 2006;66(3):1866–72.

62. Huo Z., Giger M.L., Olopade O.I. et al. Computerized analysis of digitized mammograms of BRCA1 and BRCA2 gene mutation carriers. Radiology 2002;225(2):519–26.

63. Берштейн Л.М. Гормональный канцерогенез. СПб.: Наука, 2000.

64. Берштейн Л.М. Онкоэндокринология. Традиции, современность и перспективы. СПб.: Наука, 2004.

65. Коваленко И.Г., Колесник О.С., Берштейн Л.М. Катехолэстрогены: образование, свойства и роль в канцерогенезе. Вопр онкол 1997;43(3):257–62.

66. Riza E., dos Santos Silva I., De Stavola B. et al. Urinary estrogen metabolites and mammographic parenchymal patterns in postmenopausal women. Cancer Epidemiol Biomark Prev 2001;10(6):627–34.

67. Boyd N.F., Connelly P., Byng J. et al. Plasma lipids, lipoproteins, and mammo- graphic densities. Cancer Epidemiol Biomark Prev 1995;4(7):727–33.

68. Hong C.C., Tang B.K., Rao V. et al. Cytochrome P450 1A2 (CYP1A2) activity, mammographic density, and oxidative stress: a cross-sectional study. Breast Cancer Res 2004;6(4):338–51.