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The Spectrum of Risk Lesions in Breast Pathology: Risk Factors or Cancer Precursors?

  • Kimberly AllisonEmail author
  • Kelly Mooney
Chapter

Abstract

Risk lesions of the breast are histologically, biologically, and clinically diverse, with varying associated risks of cancer development. In this chapter, the definitions of risk markers and precursor lesions are defined and explored. We summarize the contemporary paradigm of breast carcinogenesis and how atypical lesions of the breast may fit into the estrogen receptor-positive cancer development pathways. For atypical ductal hyperplasia, atypical lobular hyperplasia, flat epithelial atypia, radial scar, papilloma, and fibroepithelial lesions, evidence is summarized regarding each lesion’s (1) association with long-term overall risk of developing breast cancer and (2) possible precursor role in cancer development.

Keywords

Atypia Borderline Precursor Risk lesion Low-grade neoplasia pathway Atypical ductal hyperplasia Atypical lobular hyperplasia Flat epithelial atypia 

Abbreviations

ADH

Atypical ductal hyperplasia

ALH

Atypical lobular hyperplasia

DCIS

Ductal carcinoma in situ

ER

Estrogen receptor

FEA

Flat epithelial atypia

FEL

Fibroepithelial lesion

RS

Radial scar

References

  1. 1.
    Mayer S, Kayser G, Rücker G, Bögner D, Hirschfeld M, Hug C, et al. Absence of epithelial atypia in B3-lesions of the breast is associated with decreased risk for malignancy. Breast. 2017;31(Supplement C):144–9.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Perry N, Broeders M, de Wolf C, Törnberg S, Holland R, von Karsa L. European guidelines for quality assurance in breast cancer screening and diagnosis. Fourth edition—summary document. Ann Oncol. 2008;19(4):614–22.PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Houssami N, Ciatto S, Bilous M, Vezzosi V, Bianchi S. Borderline breast core needle histology: predictive values for malignancy in lesions of uncertain malignant potential (B3). Br J Cancer. 2007;96(8):1253–7.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Noske A, Pahl S, Fallenberg E. Flat epithelial atypia is a common subtype of B3 breast lesions and is associated with noninvasive cancer but not with invasive cancer in final excision histology. Hum Pathol. 2010;41:522–7.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Fitzgibbons PL, Henson DE, Hutter RV. Benign breast changes and the risk for subsequent breast cancer: an update of the 1985 consensus statement. Cancer Committee of the College of American Pathologists. Arch Pathol Lab Med. 1998;122(12):1053–5.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Ashbeck EL, Rosenberg RD, Stauber PM, Key CR. Benign breast biopsy diagnosis and subsequent risk of breast cancer. Cancer Epidemiol Prev Biomark. 2007;16(3):467–72.CrossRefGoogle Scholar
  7. 7.
    Sauter ER, Daly MB, editors. Breast cancer risk reduction and early detection [Internet]. Boston: Springer; 2010. [cited 2017 Oct 2]. Available from: http://link.springer.com/10.1007/978-0-387-87583-5 Google Scholar
  8. 8.
    Silvera SAN, Rohan TE. Benign proliferative epithelial disorders of the breast: a review of the epidemiologic evidence. Breast Cancer Res Treat. 2008;110(3):397–409.PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Cooper A, Royal College of Physicians of Edinburgh. Illustrations of the diseases of the breast ... Part 1 [Internet]. London: Longman, Rees, Orme, Brown, Green, and Longman; 1829 [cited 2017 Oct 2]. p. 150. Available from: http://archive.org/details/b21913249
  10. 10.
    Wellings SR, Jensen HM, Marcum RG. An atlas of subgross pathology of the human breast with special reference to possible precancerous lesions. J Natl Cancer Inst. 1975;55(2):231–73.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Simpson PT, Reis-Filho JS, Gale T, Lakhani SR. Molecular evolution of breast cancer. J Pathol. 2005;205(2):248–54.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Begg CB, Ostrovnaya I, Carniello JVS, Sakr RA, Giri D, Towers R, et al. Clonal relationships between lobular carcinoma in situ and other breast malignancies. Breast Cancer Res BCR. 2016;18(1):66.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Wellings SR, Jensen HM. On the origin and progression of ductal carcinoma in the human breast. J Natl Cancer Inst. 1973;50(5):1111–8.PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Reis-Filho JS, Simpson PT, Jones C, Steele D, Mackay A, Iravani M, et al. Pleomorphic lobular carcinoma of the breast: role of comprehensive molecular pathology in characterization of an entity. J Pathol. 2005;207(1):1–13.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Buerger H, Mommers EC, Littmann R, Simon R, Diallo R, Poremba C, et al. Ductal invasive G2 and G3 carcinomas of the breast are the end stages of at least two different lines of genetic evolution. J Pathol. 2001;194(2):165–70.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Roylance R, Gorman P, Harris W, Liebmann R, Barnes D, Hanby A, et al. Comparative genomic hybridization of breast tumors stratified by histological grade reveals new insights into the biological progression of breast cancer. Cancer Res. 1999;59(7):1433–6.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747–52.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Sørlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci. 2003;100(14):8418–23.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    van’t Veer LJ, Dai H, van de Vijver MJ, He YD, AAM H, Mao M, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415(6871):530–6.CrossRefGoogle Scholar
  20. 20.
    Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci. 2001;98(19):10869–74.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    King TA, Sakr RA, Muhsen S, Andrade VP, Giri D, Zee KJV, et al. Is there a low-grade precursor pathway in breast Cancer? Ann Surg Oncol. 2012;19(4):1115–21.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Lopez-Garcia MA, Geyer FC, Lacroix-Triki M, Marchió C, Reis-Filho JS. Breast cancer precursors revisited: molecular features and progression pathways. Histopathology. 2010;57(2):171–92.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Natrajan R, Lambros MB, Rodríguez-Pinilla SM, Moreno-Bueno G, Tan DSP, Marchió C, et al. Tiling path genomic profiling of grade 3 invasive ductal breast cancers. Clin Cancer Res. 2009;15(8):2711–22.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Natrajan R, Weigelt B, Mackay A, Geyer FC, Grigoriadis A, Tan DSP, et al. An integrative genomic and transcriptomic analysis reveals molecular pathways and networks regulated by copy number aberrations in basal-like, HER2 and luminal cancers. Breast Cancer Res Treat. 2010;121(3):575–89.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Bombonati A, Sgroi DC. The molecular pathology of breast cancer progression. J Pathol. 2011;223(2):308–18.CrossRefGoogle Scholar
  26. 26.
    Andre F, Job B, Dessen P, Tordai A, Michiels S, Liedtke C, et al. Molecular characterization of breast cancer with high-resolution oligonucleotide comparative genomic hybridization array. Clin Cancer Res Off J Am Assoc Cancer Res. 2009;15(2):441–51.CrossRefGoogle Scholar
  27. 27.
    Chin SF, Teschendorff AE, Marioni JC, Wang Y, Barbosa-Morais NL, Thorne NP, et al. High-resolution aCGH and expression profiling identifies a novel genomic subtype of ER negative breast cancer. Genome Biol. 2007;8:R215.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Jönsson G, Staaf J, Vallon-Christersson J, Ringnér M, Holm K, Hegardt C, et al. Genomic subtypes of breast cancer identified by array-comparative genomic hybridization display distinct molecular and clinical characteristics. Breast Cancer Res. 2010;12:R42.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Schnitt SJ, Collins LC. Biopsy interpretation of the breast. 2nd ed. Philadelphia: LWW; 2012. p. 512.Google Scholar
  30. 30.
    Rosen PP. Columnar cell hyperplasia is associated with lobular carcinoma in situ and tubular carcinoma. Am J Surg Pathol. 1999;23(12):1561.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Azzopardi JG, Ahmed A, Millis RR. Problems in breast pathology. Major Probl Pathol. 1979;11:i–xvi, 1–466.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Brandt SM, Young GQ, Hoda SA. The “Rosen Triad”: tubular carcinoma, lobular carcinoma in situ, and columnar cell lesions. Adv Anat Pathol. 2008;15(3):140–6.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Abdel-Fatah TMA, Powe DG, Hodi Z, Lee AHS, Reis-Filho JS, Ellis IO. High frequency of coexistence of columnar cell lesions, lobular neoplasia, and low grade ductal carcinoma in situ with invasive tubular carcinoma and invasive lobular carcinoma. Am J Surg Pathol. 2007;31(3):417–26.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Fraser JL, Raza S, Chorny K, Connolly JL, Schnitt SJ. Columnar alteration with prominent apical snouts and secretions: a spectrum of changes frequently present in breast biopsies performed for microcalcifications. Am J Surg Pathol. 1998;22(12):1521–7.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Goldstein NS, O’Malley BA. Cancerization of small ectatic ducts of the breast by ductal carcinoma in situ cells with apocrine snouts: a lesion associated with tubular carcinoma. Am J Clin Pathol. 1997;107(5):561–6.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Simpson PT, Gale T, Reis-Filho JS, Jones C, Parry S, Sloane JP, et al. Columnar cell lesions of the breast: the missing link in breast cancer progression? A morphological and molecular analysis. Am J Surg Pathol. 2005;29(6):734–46.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    McLaren BK, Gobbi H, Schuyler PA, Olson SJ, Parl FF, Dupont WD, et al. Immunohistochemical expression of estrogen receptor in enlarged lobular units with columnar alteration in benign breast biopsies: a nested case-control study. Am J Surg Pathol. 2005;29(1):105–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Webb PM, Byrne C, Schnitt SJ, Connolly JL, Jacobs T, Peiro G, et al. Family history of breast cancer, age and benign breast disease. Int J Cancer. 2002;100(3):375–8.PubMedCrossRefGoogle Scholar
  39. 39.
    Moinfar F, Man YG, Bratthauer GL. Genetic abnormalities in mammary ductal intraepithelial neoplasia-flat type (/`clinging ductal carcinoma in situ/’): a simulator of normal mammary epithelium. Cancer. 2000;88:2072–81.CrossRefGoogle Scholar
  40. 40.
    Dabbs DJ, Carter G, Fudge M, Peng Y, Swalsky P, Finkelstein S. Molecular alterations in columnar cell lesions of the breast. Mod Pathol Off J U S Can Acad Pathol Inc. 2006;19(3):344–9.Google Scholar
  41. 41.
    Sinn H-P, Elsawaf Z, Helmchen B, Aulmann S. Early breast Cancer precursor lesions: lessons learned from molecular and clinical studies. Breast Care Basel Switz. 2010;5(4):218–26.CrossRefGoogle Scholar
  42. 42.
    Elmore JG, Longton GM, Carney PA, Geller BM, Onega T, Tosteson ANA, et al. Diagnostic concordance among pathologists interpreting breast biopsy specimens. JAMA. 2015;313(11):1122–32.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Dupont WD, Page DL. Risk factors for breast cancer in women with proliferative breast disease. N Engl J Med. 1985;312(3):146–51.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Degnim AC, Visscher DW, Berman HK, Frost MH, Sellers TA, Vierkant RA, et al. Stratification of breast cancer risk in women with atypia: a mayo cohort study. J Clin Oncol. 2007;25(19):2671–7.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Hartmann LC, Radisky DC, Frost MH, Santen RJ, Vierkant RA, Benetti LL, et al. Understanding the premalignant potential of atypical hyperplasia through its natural history: a longitudinal cohort study. Cancer Prev Res Phila Pa. 2014;7(2):211–7.CrossRefGoogle Scholar
  46. 46.
    Collins LC, Baer HJ, Tamimi RM, Connolly JL, Colditz GA, Schnitt SJ. Magnitude and laterality of breast cancer risk according to histologic type of atypical hyperplasia: results from the nurses’ health study. Cancer. 2007;109(2):180–7.PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Carter CL, Corle DK, Micozzi MS, Schatzkin A, Taylor PR. A prospective study of the development of breast cancer in 16,692 women with benign breast disease. Am J Epidemiol. 1988;128(3):467–77.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    McDivitt RW, Stevens JA, Lee NC, Wingo PA, Rubin GL, Gersell D. Histologic types of benign breast disease and the risk for breast cancer. The cancer and steroid hormone study group. Cancer. 1992;69(6):1408–14.PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    London SJ, Connolly JL, Schnitt SJ, Colditz GA. A prospective study of benign breast disease and the risk of breast cancer. JAMA. 1992;267(7):941–4.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Gomes DS, Porto SS, Balabram D, Gobbi H. Inter-observer variability between general pathologists and a specialist in breast pathology in the diagnosis of lobular neoplasia, columnar cell lesions, atypical ductal hyperplasia and ductal carcinoma in situ of the breast. Diagn Pathol. 2014;9:121.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Tan PH, Ho BC-S, Selvarajan S, Yap WM, Hanby A. Pathological diagnosis of columnar cell lesions of the breast: are there issues of reproducibility? J Clin Pathol. 2005;58(7):705–9.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    O’Malley FP, Mohsin SK, Badve S, Bose S, Collins LC, Ennis M, et al. Interobserver reproducibility in the diagnosis of flat epithelial atypia of the breast. Mod Pathol Off J U S Can Acad Pathol Inc. 2006;19(2):172–9.Google Scholar
  53. 53.
    Gong G, DeVries S, Chew KL, Cha I, Ljung BM, Waldman FM. Genetic changes in paired atypical and usual ductal hyperplasia of the breast by comparative genomic hybridization. Clin Cancer Res Off J Am Assoc Cancer Res. 2001;7(8):2410–4.Google Scholar
  54. 54.
    Amari M, Suzuki A, Moriya T, Yoshinaga K, Amano G, Sasano H, et al. LOH analyses of premalignant and malignant lesions of human breast: frequent LOH in 8p, 16q, and 17q in atypical ductal hyperplasia. Oncol Rep. 1999;6(6):1277–80.PubMedPubMedCentralGoogle Scholar
  55. 55.
    Lakhani SR, Collins N, Stratton MR, Sloane JP. Atypical ductal hyperplasia of the breast: clonal proliferation with loss of heterozygosity on chromosomes 16q and 17p. J Clin Pathol. 1995;48(7):611–5.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Larson PS, de las Morenas A, Cerda SR, Bennett SR, Cupples LA, Rosenberg CL. Quantitative analysis of allele imbalance supports atypical ductal hyperplasia lesions as direct breast cancer precursors. J Pathol. 2006;209(3):307–16.PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    McDivitt RW, Hutter RV, Foote FW, Stewart FW. In situ lobular carcinoma. A prospective follow-up study indicating cumulative patient risks. JAMA. 1967;201(2):82–6.PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Bodian CA, Perzin KH, Lattes R. Lobular neoplasia. Long term risk of breast cancer and relation to other factors. Cancer. 1996;78(5):1024–34.PubMedCrossRefPubMedCentralGoogle Scholar
  59. 59.
    Page DL, Schuyler PA, Dupont WD, Jensen RA, Plummer WD, Simpson JF. Atypical lobular hyperplasia as a unilateral predictor of breast cancer risk: a retrospective cohort study. Lancet Lond Engl. 2003;361(9352):125–9.CrossRefGoogle Scholar
  60. 60.
    Lu YJ, Osin P, Lakhani SR, Di Palma S, Gusterson BA, Shipley JM. Comparative genomic hybridization analysis of lobular carcinoma in situ and atypical lobular hyperplasia and potential roles for gains and losses of genetic material in breast neoplasia. Cancer Res. 1998;58(20):4721–7.PubMedPubMedCentralGoogle Scholar
  61. 61.
    Nishizaki T, Chew K, Chu L, Isola J, Kallioniemi A, Weidner N, et al. Genetic alterations in lobular breast cancer by comparative genomic hybridization. Int J Cancer. 1997;74(5):513–7.PubMedCrossRefPubMedCentralGoogle Scholar
  62. 62.
    Hwang ES, Nyante SJ, Yi Chen Y, Moore D, DeVries S, Korkola JE, et al. Clonality of lobular carcinoma in situ and synchronous invasive lobular carcinoma. Cancer. 2004;100(12):2562–72.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Hartmann LC, Sellers TA, Frost MH, Lingle WL, Degnim AC, Ghosh K, et al. Benign breast disease and the risk of breast cancer. N Engl J Med. 2005;353(3):229–37.CrossRefGoogle Scholar
  64. 64.
    Baer HJ, Collins LC, Connolly JL, Colditz GA, Schnitt SJ, Tamimi RM. Lobule type and subsequent breast cancer risk: results from the nurses’ health studies. Cancer. 2009;115(7):1404–11.PubMedCrossRefPubMedCentralGoogle Scholar
  65. 65.
    Ottesen GL, Graversen HP, Blichert-Toft M, Zedeler K, Andersen JA. Lobular carcinoma in situ of the female breast. Short-term results of a prospective nationwide study. The Danish breast cancer cooperative group. Am J Surg Pathol. 1993;17(1):14–21.PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Sanders ME, Page DL, Simpson JF, Schuyler PA, Dale Plummer W, Dupont WD. Interdependence of radial scar and proliferative disease with respect to invasive breast carcinoma risk in patients with benign breast biopsies. Cancer. 2006;106(7):1453–61.CrossRefGoogle Scholar
  67. 67.
    Page DL, Salhany KE, Jensen RA, Dupont WD. Subsequent breast carcinoma risk after biopsy with atypia in a breast papilloma. Cancer. 1996;78(2):258–66.PubMedCrossRefPubMedCentralGoogle Scholar
  68. 68.
    Sloane JP, Mayers MM. Carcinoma and atypical hyperplasia in radial scars and complex sclerosing lesions: importance of lesion size and patient age. Histopathology. 1993;23(3):225–31.PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Anderson TJ, Battersby S. Radial scars of benign and malignant breasts: comparative features and significance. J Pathol. 1985;147(1):23–32.PubMedCrossRefPubMedCentralGoogle Scholar
  70. 70.
    Wellings SR, Alpers CE. Subgross pathologic features and incidence of radial scars in the breast. Hum Pathol. 1984;15(5):475–9.PubMedCrossRefPubMedCentralGoogle Scholar
  71. 71.
    Nielsen M, Jensen J, Andersen JA. An autopsy study of radial scar in the female breast. Histopathology. 1985;9(3):287–95.PubMedCrossRefPubMedCentralGoogle Scholar
  72. 72.
    Aroner SA, Collins LC, Connolly JL, Colditz GA, Schnitt SJ, Rosner BA, et al. Radial scars and subsequent breast cancer risk: results from the nurses’ health studies. Breast Cancer Res Treat. 2013;139(1):277–85.PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Jacobs TW, Byrne C, Colditz G, Connolly JL, Schnitt SJ. Radial scars in benign breast-biopsy specimens and the risk of breast cancer. N Engl J Med. 1999;340(6):430–6.CrossRefGoogle Scholar
  74. 74.
    Lv M, Zhu X, Zhong S, Chen W, Hu Q, Ma T, et al. Radial scars and subsequent breast cancer risk: a meta-analysis. PLoS One. 2014;9(7):e102503.PubMedCrossRefPubMedCentralGoogle Scholar
  75. 75.
    Bunting DM, Steel JR, Holgate CS, Watkins RM. Long term follow-up and risk of breast cancer after a radial scar or complex sclerosing lesion has been identified in a benign open breast biopsy. Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol. 2011;37(8):709–13.Google Scholar
  76. 76.
    Rønnov-Jessen L, Petersen OW, Bissell MJ. Cellular changes involved in conversion of normal to malignant breast: importance of the stromal reaction. Physiol Rev. 1996;76(1):69–125.PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    Mokbel K, Price RK, Mostafa A, Williams N, Wells CA, Perry N, et al. Radial scar and carcinoma of the breast: microscopic findings in 32 cases. Breast Edinb Scotl. 1999;8(6):339–42.CrossRefGoogle Scholar
  78. 78.
    Alvarado-Cabrero I, Tavassoli FA. Neoplastic and malignant lesions involving or arising in a radial scar: a clinicopathologic analysis of 17 cases. Breast J. 2000;6(2):96–102.PubMedCrossRefPubMedCentralGoogle Scholar
  79. 79.
    Patterson JA, Scott M, Anderson N, Kirk SJ. Radial scar, complex sclerosing lesion and risk of breast cancer. Analysis of 175 cases in Northern Ireland. Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol. 2004;30(10):1065–8.Google Scholar
  80. 80.
    Iqbal M, Shoker BS, Foster CS, Jarvis C, Sibson DR, Davies MPA. Molecular and genetic abnormalities in radial scar. Hum Pathol. 2002;33(7):715–22.PubMedCrossRefPubMedCentralGoogle Scholar
  81. 81.
    Fisher ER, Palekar AS, Kotwal N, Lipana N. A nonencapsulated sclerosing lesion of the breast. Am J Clin Pathol. 1979;71(3):240–6.PubMedCrossRefPubMedCentralGoogle Scholar
  82. 82.
    Adair FE. Sanguineous discharge from the nipple and its significance in relation to cancer of the breast: a study based on 108 cases. Ann Surg. 1930;91(2):197–209.PubMedCrossRefPubMedCentralGoogle Scholar
  83. 83.
    Carter D. Intraductal papillary tumors of the breast: a study of 78 cases. Cancer. 1977;39(4):1689–92.PubMedCrossRefPubMedCentralGoogle Scholar
  84. 84.
    Lewison EF, Lyons JG. Relationship between benign breast disease and cancer. AMA Arch Surg. 1953;66(1):94–114.PubMedCrossRefPubMedCentralGoogle Scholar
  85. 85.
    Haagensen CD, Stout AP, Phillips JS. The papillary neoplasms of the breast. I. Benign intraductal papilloma. Ann Surg. 1951;133(1):18–36.PubMedCrossRefPubMedCentralGoogle Scholar
  86. 86.
    Buhl-Jorgensen SE, Fischermann K, Johansen H, Petersen B. Cancer risk in intraductal papilloma and papillomatosis. Surg Gynecol Obstet. 1968;127(6):1307–12.PubMedPubMedCentralGoogle Scholar
  87. 87.
    Kilgore AR, Fleming R, Ramos MM. The incidence of cancer with nipple discharge and the risk of cancer in the presence of papillary disease of the breast. Surg Gynecol Obstet. 1953;96(6):649–60.PubMedPubMedCentralGoogle Scholar
  88. 88.
    Mulligan AM, O’malley FP. Papillary lesions of the breast: a review. Adv Anat Pathol. 2007;14(2):108–19.PubMedCrossRefPubMedCentralGoogle Scholar
  89. 89.
    Lewis JT, Hartmann LC, Vierkant RA, Maloney SD, Shane Pankratz V, Allers TM, et al. An analysis of breast cancer risk in women with single, multiple, and atypical papilloma. Am J Surg Pathol. 2006;30(6):665–72.PubMedCrossRefPubMedCentralGoogle Scholar
  90. 90.
    Ciatto S, Andreoli C, Cirillo A, Bonardi R, Bianchi S, Santoro G, et al. The risk of breast cancer subsequent to histologic diagnosis of benign intraductal papilloma follow-up study of 339 cases. Tumori. 1991;77(1):41–3.PubMedCrossRefPubMedCentralGoogle Scholar
  91. 91.
    Pellettiere EV. The clinical and pathologic aspects of papillomatous disease of the breast: a follow-up study of 97 patients treated by local excision. Am J Clin Pathol. 1971;55(6):740–8.PubMedCrossRefPubMedCentralGoogle Scholar
  92. 92.
    Ali-Fehmi R, Carolin K, Wallis T, Visscher DW. Clinicopathologic analysis of breast lesions associated with multiple papillomas. Hum Pathol. 2003;34(3):234–9.PubMedCrossRefPubMedCentralGoogle Scholar
  93. 93.
    Noguchi S, Motomura K, Inaji H, Imaoka S, Koyama H. Clonal analysis of solitary intraductal papilloma of the breast by means of polymerase chain reaction. Am J Pathol. 1994;144(6):1320–5.PubMedPubMedCentralGoogle Scholar
  94. 94.
    Noguchi S, Aihara T, Koyama H, Motomura K, Inaji H, Imaoka S. Clonal analysis of benign and malignant human breast tumors by means of polymerase chain reaction. Cancer Lett. 1995;90(1):57–63.PubMedCrossRefPubMedCentralGoogle Scholar
  95. 95.
    Tsuda H, Takarabe T, Inazawa J, Hirohashi S. Detection of numerical alterations of chromosomes 3, 7, 17 and X in low-grade Intracystic papillary tumors of the breast by multi-color fluorescence in situ hybridization. Breast Cancer Tokyo Jpn. 1997;4(4):247–52.CrossRefGoogle Scholar
  96. 96.
    Lininger RA, Park WS, Man YG, Pham T, MacGrogan G, Zhuang Z, et al. LOH at 16p13 is a novel chromosomal alteration detected in benign and malignant microdissected papillary neoplasms of the breast. Hum Pathol. 1998;29(10):1113–8.PubMedCrossRefPubMedCentralGoogle Scholar
  97. 97.
    Di Cristofano C, Mrad K, Zavaglia K, Bertacca G, Aretini P, Cipollini G, et al. Papillary lesions of the breast: a molecular progression? Breast Cancer Res Treat. 2005;90(1):71–6.PubMedCrossRefPubMedCentralGoogle Scholar
  98. 98.
    Boecker W, Buerger H, Schmitz K, Ellis IA, van Diest PJ, Sinn HP, et al. Ductal epithelial proliferations of the breast: a biological continuum? Comparative genomic hybridization and high-molecular-weight cytokeratin expression patterns. J Pathol. 2001;195(4):415–21.PubMedCrossRefPubMedCentralGoogle Scholar
  99. 99.
    Dietrich CU, Pandis N, Teixeira MR, Bardi G, Gerdes AM, Andersen JA, et al. Chromosome abnormalities in benign hyperproliferative disorders of epithelial and stromal breast tissue. Int J Cancer. 1995;60(1):49–53.PubMedCrossRefPubMedCentralGoogle Scholar
  100. 100.
    Komoike Y, Motomura K, Inaji H, Koyama H. Diagnosis of ductal carcinoma in situ (DCIS) and intraductal papilloma using fluorescence in situ hybridization (FISH) analysis. Breast Cancer Tokyo Jpn. 2000;7(4):332–6.CrossRefGoogle Scholar
  101. 101.
    Troxell ML, Levine J, Beadling C, Warrick A, Dunlap J, Presnell A, et al. High prevalence of PIK3CA/AKT pathway mutations in papillary neoplasms of the breast. Mod Pathol. 2009;23(1):27–37.PubMedCrossRefPubMedCentralGoogle Scholar
  102. 102.
    Dupont WD, Page DL, Parl FF, Vnencak-Jones CL, Plummer WDJ, Rados MS, et al. Long-term risk of breast cancer in women with Fibroadenoma. N Engl J Med. 1994;331(1):10–5.PubMedCrossRefPubMedCentralGoogle Scholar
  103. 103.
    Carter BA, Page DL, Schuyler P, Parl FF, Simpson JF, Jensen RA, et al. No elevation in long-term breast carcinoma risk for women with fibroadenomas that contain atypical hyperplasia. Cancer. 2001;92(1):30–6.PubMedCrossRefPubMedCentralGoogle Scholar
  104. 104.
    Nassar A, Visscher DW, Degnim AC, Frank RD, Vierkant RA, Frost M, et al. Complex fibroadenoma and breast cancer risk: a mayo clinic benign breast disease cohort study. Breast Cancer Res Treat. 2015;153(2):397–405.PubMedCrossRefPubMedCentralGoogle Scholar
  105. 105.
    Hua B, Xu J-Y, Jiang L, Wang Z. Fibroadenoma with an unexpected lobular carcinoma in situ: a case report and review of the literature. Oncol Lett. 2015;10(3):1397–401.PubMedCrossRefPubMedCentralGoogle Scholar
  106. 106.
    Buzanowski-Konakry K, Harrison EG, Payne WS. Lobular carcinoma arising in fibroadenoma of the breast. Cancer. 1975;35(2):450–6.PubMedCrossRefPubMedCentralGoogle Scholar
  107. 107.
    Diaz NM, Palmer JO, McDivitt RW. Carcinoma arising within fibroadenomas of the breast. A clinicopathologic study of 105 patients. Am J Clin Pathol. 1991;95(5):614–22.PubMedCrossRefPubMedCentralGoogle Scholar
  108. 108.
    Fives C, O’Neill CJ, Murphy R, Corrigan MA, O’Sullivan MJ, Feeley L, et al. When pathological and radiological correlation is achieved, excision of fibroadenoma with lobular neoplasia on core biopsy is not warranted. Breast Edinb Scotl. 2016;30:125–9.CrossRefGoogle Scholar
  109. 109.
    Lawton TJ, Acs G, Argani P, Farshid G, Gilcrease M, Goldstein N, et al. Interobserver variability by pathologists in the distinction between cellular fibroadenomas and phyllodes tumors. Int J Surg Pathol. 2014;22(8):695–8.PubMedCrossRefPubMedCentralGoogle Scholar
  110. 110.
    Krings G, Bean GR, Chen Y-Y. Fibroepithelial lesions; the WHO spectrum. Semin Diagn Pathol. 2017;34(5):438–52.PubMedCrossRefPubMedCentralGoogle Scholar
  111. 111.
    Tan PH, Thike AA, Tan WJ, Thu MMM, Busmanis I, Li H, et al. Predicting clinical behaviour of breast phyllodes tumours: a nomogram based on histological criteria and surgical margins. J Clin Pathol. 2012;65(1):69–76.PubMedCrossRefPubMedCentralGoogle Scholar
  112. 112.
    Tan WJ, Cima I, Choudhury Y, Wei X, Lim JCT, Thike AA, et al. A five-gene reverse transcription-PCR assay for pre-operative classification of breast fibroepithelial lesions. Breast Cancer Res BCR. 2016;18(1):31.PubMedCrossRefPubMedCentralGoogle Scholar
  113. 113.
    Yasir S, Gamez R, Jenkins S, Visscher DW, Nassar A. Significant histologic features differentiating cellular fibroadenoma from phyllodes tumor on core needle biopsy specimens. Am J Clin Pathol. 2014;142(3):362–9.PubMedCrossRefPubMedCentralGoogle Scholar
  114. 114.
    Tse GMK, Lee CS, Kung FYL, Scolyer RA, Law BKB, Lau T, et al. Hormonal receptors expression in epithelial cells of mammary phyllodes tumors correlates with pathologic grade of the tumor: a multicenter study of 143 cases. Am J Clin Pathol. 2002;118(4):522–6.PubMedCrossRefPubMedCentralGoogle Scholar
  115. 115.
    Jacobs TW, Chen Y-Y, Guinee DG, Holden JA, Cha I, Bauermeister DE, et al. Fibroepithelial lesions with cellular stroma on breast core needle biopsy: are there predictors of outcome on surgical excision? Am J Clin Pathol. 2005;124(3):342–54.PubMedCrossRefPubMedCentralGoogle Scholar
  116. 116.
    Lu YJ, Birdsall S, Osin P, Gusterson B, Shipley J. Phyllodes tumors of the breast analyzed by comparative genomic hybridization and association of increased 1q copy number with stromal overgrowth and recurrence. Genes Chromosomes Cancer. 1997;20(3):275–81.PubMedCrossRefPubMedCentralGoogle Scholar
  117. 117.
    Yoshida M, Sekine S, Ogawa R, Yoshida H, Maeshima A, Kanai Y, et al. Frequent MED12 mutations in phyllodes tumours of the breast. Br J Cancer. 2015;112(10):1703–8.PubMedCrossRefPubMedCentralGoogle Scholar
  118. 118.
    Piscuoglio S, Murray M, Fusco N, Marchiò C, Loo FL, Martelotto LG, et al. MED12 somatic mutations in fibroadenomas and phyllodes tumours of the breast. Histopathology. 2015;67(5):719–29.PubMedCrossRefPubMedCentralGoogle Scholar
  119. 119.
    Nagasawa S, Maeda I, Fukuda T, Wu W, Hayami R, Kojima Y, et al. MED12 exon 2 mutations in phyllodes tumors of the breast. Cancer Med. 2015;4(7):1117–21.PubMedCrossRefPubMedCentralGoogle Scholar
  120. 120.
    Cani AK, Hovelson DH, McDaniel AS, Sadis S, Haller MJ, Yadati V, et al. Next-gen sequencing exposes frequent MED12 mutations and actionable therapeutic targets in phyllodes tumors. Mol Cancer Res MCR. 2015;13(4):613–9.PubMedCrossRefPubMedCentralGoogle Scholar
  121. 121.
    Laé M, Vincent-Salomon A, Savignoni A, Huon I, Fréneaux P, Sigal-Zafrani B, et al. Phyllodes tumors of the breast segregate in two groups according to genetic criteria. Mod Pathol Off J U S Can Acad Pathol Inc. 2007;20(4):435–44.Google Scholar
  122. 122.
    Jones AM, Mitter R, Springall R, Graham T, Winter E, Gillett C, et al. A comprehensive genetic profile of phyllodes tumours of the breast detects important mutations, intra-tumoral genetic heterogeneity and new genetic changes on recurrence. J Pathol. 2008;214(5):533–44.PubMedCrossRefPubMedCentralGoogle Scholar
  123. 123.
    Lv S, Niu Y, Wei L, Liu Q, Wang X, Chen Y. Chromosomal aberrations and genetic relations in benign, borderline and malignant phyllodes tumors of the breast: a comparative genomic hybridization study. Breast Cancer Res Treat. 2008;112(3):411–8.PubMedCrossRefPubMedCentralGoogle Scholar
  124. 124.
    Noguchi S, Motomura K, Inaji H, Imaoka S, Koyama H. Clonal analysis of fibroadenoma and phyllodes tumor of the breast. Cancer Res. 1993;53(17):4071–4.PubMedPubMedCentralGoogle Scholar
  125. 125.
    Noguchi S, Yokouchi H, Aihara T, Motomura K, Inaji H, Imaoka S, et al. Progression of fibroadenoma to phyllodes tumor demonstrated by clonal analysis. Cancer. 1995;76(10):1779–85.PubMedCrossRefPubMedCentralGoogle Scholar
  126. 126.
    Sawyer EJ, Hanby AM, Ellis P, Lakhani SR, Ellis IO, Boyle S, et al. Molecular analysis of phyllodes tumors reveals distinct changes in the epithelial and stromal components. Am J Pathol. 2000;156(3):1093–8.PubMedCrossRefPubMedCentralGoogle Scholar
  127. 127.
    Sawyer EJ, Hanby AM, Rowan AJ, Gillett CE, Thomas RE, Poulsom R, et al. The Wnt pathway, epithelial-stromal interactions, and malignant progression in phyllodes tumours. J Pathol. 2002;196(4):437–44.PubMedCrossRefPubMedCentralGoogle Scholar
  128. 128.
    Wang ZC, Buraimoh A, Iglehart JD, Richardson AL. Genome-wide analysis for loss of heterozygosity in primary and recurrent phyllodes tumor and fibroadenoma of breast using single nucleotide polymorphism arrays. Breast Cancer Res Treat. 2006;97(3):301–9.PubMedCrossRefPubMedCentralGoogle Scholar
  129. 129.
    Sawhney N, Garrahan N, Douglas-Jones AG, Williams ED. Epithelial – stromal interactions in tumors. A morphologic study of fibroepithelial tumors of the breast. Cancer. 1992;70(8):2115–20.PubMedCrossRefPubMedCentralGoogle Scholar
  130. 130.
    Mooney KL, Bassett LW, Apple SK. Upgrade rates of high-risk breast lesions diagnosed on core needle biopsy: a single-institution experience and literature review. Mod Pathol. 2016;29(12):1471–84.PubMedCrossRefPubMedCentralGoogle Scholar
  131. 131.
    Cancer of the breast (female) – SEER cancer stat facts [Internet]. [cited 2017 Oct 2]. Available from: https://seer.cancer.gov/statfacts/html/breast.html
  132. 132.
    Cheeney S, Rahbar H, Dontchos BN, Javid SH, Rendi MH, Partridge SC. Apparent diffusion coefficient values may help predict which MRI-detected high-risk breast lesions will upgrade at surgical excision. J Magn Reson Imaging JMRI. 2017;46(4):1028–36.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PathologyStanford University, School of MedicinePalo AltoUSA

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