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The Sick Lobe Concept

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Breast Cancer

Abstract

Breast cancer is the most common malignancy among younger women worldwide [Boyle, Ferlay, Ann Oncol 16(3):481–8, 2005]. Women are at 100 times higher risk of getting breast cancer during their lifetime than men. The lifetime risk of getting the disease is, at least, fivefold higher in carriers of mutated BRCA1 and BRCA2 genes than in the normal population [Easton et al., Am J Hum Genet 61:120–8, 1997; Ford et al., Lancet 343: 692–5, 1994]. Certain geographic areas in the USA, Europe, Australia, and Canada are well known for their exceptionally high breast cancer incidence [Clarke et al., Breast Cancer Res 4:R13, 2002 ]. Female gender, carrying a mutated gene, living in a high-incidence country, and many other known cancer risk factors are characteristics of the entire organism and influence the genetic construction, as well as the milieu, of all the cells in the body. However, breast cancer develops in one quadrant of one breast in the vast majority of cases. This simple observation indicates presence of at-risk tissue in the breast that is more sensitive to oncogenic stimuli than the other structures of the human body. In our view, this at-risk tissue corresponds to a sick breast lobe [Tot, Virchows Arch 447:1–8, 2005].

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References

  1. Boyle P, Ferlay J. Cancer incidence and mortality in Europe 2004. Ann Oncol. 2005;16(3):481–8.

    Article  PubMed  CAS  Google Scholar 

  2. Easton DF, Steele L, Fields P, et al. Cancer risk in two large breast cancer families linked to BRCA2 on chromosome 13q12-13. Am J Hum Genet. 1997;61:120–8.

    Article  PubMed  CAS  Google Scholar 

  3. Ford D, Easton DF, Bishop DT, et al. Risk of cancer in BRCA1-mutation carriers. Breast cancer linkage consortium. Lancet. 1994;343:692–5.

    Article  PubMed  CAS  Google Scholar 

  4. Clarke CA, Glaser SL, West DW, et al. Breast cancer incidence and mortality trends in an affluent population: Marine county, California, USA, 1990-1996. Breast Cancer Res. 2002;4:R13.

    Article  PubMed  Google Scholar 

  5. Tot T. DCIS, cytokeratins, and the theory of the sick lobe. Virchows Arch. 2005;447:1–8.

    Article  PubMed  Google Scholar 

  6. Going JJ, Moffat DF. Escaping from flatland: clinical and biological aspects of human mammary duct anatomy in three dimensions. J Pathol. 2004;203:538–44.

    Article  PubMed  Google Scholar 

  7. Going JJ, Mohun TJ. Human breast duct anatomy, the ‘sick lobe’ hypothesis and intraductal approaches to breast cancer. Breast Cancer Res Treat. 2006;97:285–91.

    Article  PubMed  Google Scholar 

  8. Going JJ. Lobar anatomy of the human breast and its importance for breast cancer. In: Tot T, editor. Breast cancer—a lobar disease. New York: Springer; 2011. p. 19–37.

    Google Scholar 

  9. Amy D. Lobar ultrasound of the breast. In: Tot T, editor. Breast cancer—a lobar disease. New York: Springer; 2011. p. 153–62.

    Google Scholar 

  10. Gudjonsson T, Magnusson MK. Stem cell biology and the pathways of carcinogenesis. APMIS. 2005;113:922–9.

    Article  PubMed  Google Scholar 

  11. Fridriksdottir AJR, Petersen OW, Ronnow-Jessen L. Mammary gland stem cells: current status and future challenges. Int J Dev Biol. 2011;55:719–29.

    Article  PubMed  Google Scholar 

  12. Tot T. The theory of the sick lobe. In: Tot T, editor. Breast cancer—a lobar disease. New York: Springer; 2011. p. 1–17.

    Chapter  Google Scholar 

  13. Villadsen R. In search of stem cell hierarchy in the human breast and its relevance in breast cancer evolution. APMIS. 2005;113:903–21.

    Article  PubMed  Google Scholar 

  14. Villadsen R, Fridriksdottir AJ, Ronnov-Jenssen L, et al. Evidence for stem cell hierarchy in the adult human breast. J Cell Biol. 2007;177:87–101.

    Article  PubMed  CAS  Google Scholar 

  15. Smith GH, Boulanger CA. Epithelial stem cells transplantation and self renewal analysis. Cell Prolif. 2003;36 Suppl 1:3–15.

    Article  PubMed  CAS  Google Scholar 

  16. Al Hajj M, Wicha MS, Benito-Hernandez A, et al. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 2003;100:3983–8.

    Article  PubMed  CAS  Google Scholar 

  17. Reja T, Morrison SJ, Clarke MF, Weissmann IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414:105–11.

    Article  Google Scholar 

  18. Agelopoulos K, Buerger H, Brandt B. Allelic imbalance of the egfr gene as key event in breast cancer progression—the concept of committed progenitor cells. Curr Cancer Drug Targets. 2008;8:431–45.

    Article  PubMed  CAS  Google Scholar 

  19. Tot T. The theory of the sick breast lobe and the possible consequences. Int J Surg Pathol. 2007;15:369–75.

    Article  PubMed  Google Scholar 

  20. Tot T. The origins of early breast carcinoma. Semin Diagn Pathol. 2010;27:62–8.

    Article  PubMed  Google Scholar 

  21. Tot T, editor. Breast cancer—a lobar disease. New York: Springer; 2011.

    Google Scholar 

  22. Virchow R. Cellular-Pathologie. Archiv fur Pathologische Anatomie und Phisiologie fur Klinische Medizin. 1855;8:3–39.

    Google Scholar 

  23. Gibbs NM. Large paraffin sections and chemical clearance of axillary tissues as a routine procedure in the pathological examination of the breast. Histopathology. 1982;6(5):647–60.

    Article  PubMed  CAS  Google Scholar 

  24. Mai KT, Yazdi HM, Burns BF, Perkins DG. Pattern of distribution of intraductal and infiltrating ductal carcinoma: three-dimensional study using serial coronal giant sections of the breast. Hum Pathol. 2000;31:464–74.

    Article  PubMed  CAS  Google Scholar 

  25. Xue F, Michels KB. Intrauterine factors and risk of breast cancer: a systematic review and meta-analysis of current evidence. Lancet Oncol. 2007;8:1088–100.

    Article  PubMed  Google Scholar 

  26. Yan PS, Venkataramu C, Ibrahim A, et al. Mapping geographic zones of cancer risk with epigenetic biomarkers in normal breast tissue. Clin Cancer Res. 2006;12:6626–36.

    Article  PubMed  CAS  Google Scholar 

  27. Lakhani SR, Chaggar R, Davies S, et al. Genetic alterations in “normal” luminal and myoepithelial cells of the breast. J Pathol. 1999;189:496–503.

    Article  PubMed  CAS  Google Scholar 

  28. Barchie MF, Clive KS, Tyler JA, et al. Standardized pretreatment breast MRI-accuracy and influence on mastectomy decisions. J Surg Oncol. 2011;104(7):741–5.

    Article  PubMed  Google Scholar 

  29. Teboul M, Halliwell M. Atlas of ultrasound and ductal echography of the breast: the introduction of anatomic intelligence into breast imaging. London: Wiley-Blackwell; 1995. p. 380.

    Google Scholar 

  30. Tabár L, Chen HT, Yen MFA, et al. Mammographic tumor features can predict long-term outcomes reliably in women with 1-14 mm invasive carcinoma. Cancer. 2004;101:1745–59.

    Article  PubMed  Google Scholar 

  31. Andersen JA, Blichert-Toft M, Dyreborg U. In situ carcinomas of the breast. Types, growth pattern, diagnosis and treatment. Eur J Surg Oncol. 1987;13:105–11.

    PubMed  CAS  Google Scholar 

  32. Tot T. The subgross morphology of normal and pathologically altered breast tissue. In: Suri J, Rangayyan RM, editors. Recent advances in breast imaging, mammography and computer—aided diagnosis of breast cancer. Bellingham, WA: SPIE Press; 2006. p. 1–49.

    Chapter  Google Scholar 

  33. Tot T. The clinical relevance of the distribution of the lesions in 500 consecutive breast cancer cases documented in large-format histological sections. Cancer. 2007;110:2551–60.

    Article  PubMed  Google Scholar 

  34. Tot T. General morphology of benign and malignant breast lesions: old parameters in new perspectives. In: Suri J, Rangayyan RM, Laxminarayan S, editors. Emerging technologies in breast imaging and mammography. Valencia, CA: American Scientific Publisher; 2008. p. 1–12.

    Google Scholar 

  35. de Neergaard M, Kim J, Villadsen R, et al. Epithelial-stromal interaction 1 (EPSTI1) substitutes for peritumoral fibroblasts in the tumor microenvironment. Am J Pathol. 2010;176(3): 1229–40.

    Article  PubMed  Google Scholar 

  36. Asioli S, Eusebi V, Gaetano L, et al. The pre-lymphatic pathway, the roots of the lymphatic system in the breast tissue: a 3D study. Virchows Arch. 2008;453:401–6.

    Article  PubMed  Google Scholar 

  37. Tot T. The diffuse type of invasive lobular carcinoma of the breast: morphology and prognosis. Virchows Arch. 2003;443:718–24.

    Article  PubMed  Google Scholar 

  38. Tot T, Kahán Z. A new approach to early breast cancer. In: Kahán Z, Tot T, editors. Breast cancer, a heterogeneous disease entity. The very early stages. New York: Springer; 2011. p. 1–22.

    Chapter  Google Scholar 

  39. Clarke GM, Eidt S, Sun L, et al. Whole-specimen histopathology: a method to produce whole mount breast serial sections for 3-D digital histopathology imaging. Histopathology. 2007;50:232–42.

    Article  PubMed  CAS  Google Scholar 

  40. Egan RL. Multicentric breast carcinoma: clinical-radiographic-pathologic whole organ studies and 10-year survival. Cancer. 1982;49:1123–30.

    Article  PubMed  CAS  Google Scholar 

  41. Gallager HS, Martin JE. The study of mammary carcinoma by mammography and whole organ sectioning. Early observations. Cancer. 1969;23:855–73.

    Article  PubMed  CAS  Google Scholar 

  42. Holland R, Veling SH, Mravunac M, et al. Histologic multifocality of Tis, T1-2 breast carcinomas. Implications for clinical trials of breast conserving surgery. Cancer. 1985;56:979–90.

    Article  PubMed  CAS  Google Scholar 

  43. Foschini MP, Tot T, Eusebi V. Large section (macrosection) histologic slides. In: Silverstein MJ, editor. Ductal carcinoma in situ of the breast. 2nd ed. Philadelphia, PA: Lippincott, Williams and Wilkins; 2002. p. 249–54.

    Google Scholar 

  44. Foschini MP, Flamminio F, Miglio R, et al. The impact of large sections on the study of in situ and invasive duct carcinoma of the breast. Hum Pathol. 2007;38:1736–43.

    Article  PubMed  Google Scholar 

  45. Jackson PA, Merchant W, McCormick CJ, Cook MG. A comparison of large block macrosectioning and conventional techniques in breast pathology. Virchows Arch. 1994;425:243–8.

    Article  PubMed  CAS  Google Scholar 

  46. Mechine-Neuville MP, Chenard B, Gairard C, et al. Large sections in routine breast pathology. A technique adapted to conservative surgery. Ann Pathol. 2000;20:275–9.

    PubMed  CAS  Google Scholar 

  47. Tot T. The metastastic capacity of multifocal breast carcinomas: extensive tumors versus tumors of limited extent. Hum Pathol. 2009;40:199–205.

    Article  PubMed  Google Scholar 

  48. Tot T, Gy P, Hofmeyer S, et al. The distribution of lesions in 1-14-mm invasive breast carcinomas and its relation to metastatic potential. Virchows Arch. 2009;455:109–15.

    Article  PubMed  CAS  Google Scholar 

  49. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), Darby S, McGale P, Correa C, et al. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet. 2011;378(9804):1707–16.

    Article  PubMed  CAS  Google Scholar 

  50. Simone NL, Dan T, Shih J, et al. Twenty-five year results of the National Cancer Institute randomized breast conservation trial. Breast Cancer Res Treat. 2012;132(1):197–203.

    Article  PubMed  Google Scholar 

  51. Silverstein MJ, Lagios MD. Choosing treatment for patients with ductal carcinoma in situ: fine tuning the University of Southern California/Van Nuys Prognostic Index. J Natl Cancer Inst Monogr. 2010;41:193–6.

    Article  Google Scholar 

  52. Tot T. Subgross morphology, the sick lobe hypothesis, and the success of breast conservation. Int J Breast Cancer. 2011;2011:634021. doi:10.4061/2011/634021. Article ID 634021, 8 p.

    PubMed  Google Scholar 

  53. Lindquist D, Hellberg D, Tot T. Disease extent ≥4cm is a prognostic marker of local recurrence in T1-2 breast cancer. Patholog Res Int. 2011;2011:860584.

    PubMed  CAS  Google Scholar 

  54. Faverly DRG, Hendricks JHCL, Holland R. Breast carcinoma of limited extent. Frequency, radiologic—pathologic characteristics, and surgical margin requirements. Cancer. 2001;91: 647–59.

    Article  PubMed  CAS  Google Scholar 

  55. Holland R, Hendricks JH, Vebeek AL, et al. Extent, distribution, and mammographic/histological correlation of breast ductal carcinoma in situ. Lancet. 1990;335:519–22.

    Article  PubMed  CAS  Google Scholar 

  56. Dooley WC. Routine operative breast endoscopy during lumpectomy. Ann Surg Oncol. 2003;10:38–42.

    Article  PubMed  Google Scholar 

  57. Tot T, Gere M, Gy P, et al. Breast cancer multifocality, disease extent, and survival. Hum Pathol. 2011;42(11):1761–9.

    Article  PubMed  Google Scholar 

  58. Andea AA, Wallis T, Newman LA, et al. Pathologic analysis of tumor size and lymph node status in multifocal/multicentric breast carcinoma. Cancer. 2002;94:1383.1390.

    Article  PubMed  Google Scholar 

  59. Coombs NJ, Boyages J. Multifocal and multicentric breast cancer: does each focus matter? J Clin Oncol. 2005;34:7497–502.

    Article  Google Scholar 

  60. Pedersen L, Gunnarsdottir KA, Rasmussen BB, et al. The prognostic influence of multifocality in breast cancer patients. Breast. 2004;13:188–93.

    Article  PubMed  CAS  Google Scholar 

  61. Boyages J, Jajashinghe UW, Coombs N. Multifocal breast cancer and survival: each focus does matter particularly for larger tumours. Eur J Cancer. 2010;46:1990–6.

    Article  PubMed  Google Scholar 

  62. Weissenbacher TM, Zschage M, Janni W, et al. Multicentric and multifocal versus unifocal breast cancer: is the tumor-node-metastasis classification justified? Breast Cancer Res Treat. 2010;22:27–34.

    Article  Google Scholar 

  63. Chung AP, Huynh K, Kidner T, et al. Comparison of outcomes of breast conserving therapy in multifocal and unifocal invasive breast cancer. Am Coll Surg. 2012;215:137–47.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology and Clinical Cytology, Central Hospital Falun, Central Hospital, Falun, Sweden

    Tibor Tot M.D., Ph.D.

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  1. Tibor Tot M.D., Ph.D.
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Correspondence to Tibor Tot M.D., Ph.D. .

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Editors and Affiliations

  1. Department of Surgery, Rush University Medical Center, Chicago, Illinois, USA

    Darius S. Francescatti

  2. Hoag Breast Program, Hoag Memorial Hospital Presbyterian, Newport Beach, California, USA

    Melvin J. Silverstein

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Tot, T. (2014). The Sick Lobe Concept. In: Francescatti, D., Silverstein, M. (eds) Breast Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8063-1_3

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  • DOI: https://doi.org/10.1007/978-1-4614-8063-1_3

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