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Histological and molecular types of breast cancer: is there a unifying taxonomy?

Abstract

Breast cancer is a complex and heterogeneous disease, comprising multiple tumor entities associated with distinctive histological patterns and different biological features and clinical behaviors. Microarray-based high-throughput technologies have been employed to unravel the molecular characteristics of breast cancer, including its proclivity to disseminate to distant sites, and the molecular basis for histological grade. In addition, a breast cancer molecular taxonomy based solely on transcriptomic analysis has been proposed. Most microarray studies have focused on invasive ductal carcinomas of no special type, neglecting the important information about the biology and clinical behavior of breast cancers conveyed by histological type. Histological special types of breast cancer account for up to 25% of all invasive breast cancers. The histopathological characteristics of these cancers might be driven by specific genetic alterations, providing direct evidence for genotypic–phenotypic correlations between morphological patterns and molecular changes in breast cancer. We review the historical aspects of breast cancer taxonomy, discuss the possible origins of the diversity of breast cancer and propose an approach for the identification of novel therapeutic targets on the basis of histological special types of breast cancer.

Key Points

  • Breast cancer special types account for up to 25% of all invasive breast cancers and have distinct histological features and clinical implications

  • The relative rarity of each type, other than lobular, tubular, medullary and metaplastic tumors, renders them difficult to study in advanced molecular studies

  • Some special types of breast cancer are driven by a constellation of specific genetic aberrations (for example, metaplastic breast cancers often harbor dysfunctional p53 and BRCA1 pathways)

  • Each special type, apart from invasive lobular and apocrine carcinomas, is more homogeneous than invasive ductal carcinomas of no special type at the genomic, transcriptomic and immunohistochemical levels

  • Owing to their more homogeneous molecular make-up, studying special types of breast cancer could lead to the identification of novel therapeutic targets

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Figure 1: Histological special types of breast cancer.
Figure 2: Histological special types and molecular subtypes.
Figure 3: Theoretical models that explain breast cancer histological special types.
Figure 4: The low-grade breast neoplasia family.

References

  1. Reis-Filho, J. S. & Lakhani, S. R. Breast cancer special types: why bother? J. Pathol. 216, 394–398 (2008).

    Article  CAS  PubMed  Google Scholar 

  2. Simpson, P. T., Reis-Filho, J. S., Gale, T. & Lakhani, S. R. Molecular evolution of breast cancer. J. Pathol. 205, 248–254 (2005).

    Article  CAS  PubMed  Google Scholar 

  3. Vargo-Gogola, T. & Rosen, J. M. Modelling breast cancer: one size does not fit all. Nat. Rev. Cancer 7, 659–672 (2007).

    Article  CAS  PubMed  Google Scholar 

  4. Perou, C. M. et al. Molecular portraits of human breast tumours. Nature 406, 747–752 (2000).

    CAS  Article  PubMed  Google Scholar 

  5. Sorlie, T. et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc. Natl Acad. Sci. USA 98, 10869–10874 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Sorlie, T. et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc. Natl Acad. Sci. USA 100, 8418–8423 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Hu, Z. et al. The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics 7, 96 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Scarff, R. W. & Torloni, H. Histological Typing of Breast Tumours (WHO, Geneva, 1968).

    Google Scholar 

  9. Azzopardi, J. G., Ahmed, A. & Millis, R. R. Problems in Breast Pathology (W. B. Saunders Company Ltd, London, 1979).

    Google Scholar 

  10. Azzopardi, J. G. et al. The World Health Organization histological typing of breast tumors: second edition. The World Health Organization. Am. J. Clin. Pathol. 78, 806–816 (1982).

    Article  Google Scholar 

  11. Huvos, A. G., Lucas, J. C. Jr & Foote, F. W. Jr. Metaplastic breast carcinoma: rare form of mammary cancer. NY State J. Med. 73, 1078–1082 (1973).

    CAS  Google Scholar 

  12. Tavassoli, F. A. Pathology of the Breast (Appleton & Lange, Stamford, 1999).

    Google Scholar 

  13. Rosen, P. P. Rosen's Breast Pathology (Lippincott Williams & Wilkins, Philadelphia, 2001).

    Google Scholar 

  14. Page, D. L. & Anderson, T. J. Diagnostic Histopathology of the Breast (Churchill Livingstone, Edinburgh, 1987).

    Google Scholar 

  15. Elston, C. W. & Ellis, I. O. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 19, 403–410 (1991).

    Article  CAS  PubMed  Google Scholar 

  16. Ellis, I. O. et al. Pathological prognostic factors in breast cancer. II. Histological type: relationship with survival in a large study with long-term follow-up. Histopathology 20, 479–489 (1992).

    Article  CAS  PubMed  Google Scholar 

  17. Longacre, T. A. et al. Interobserver agreement and reproducibility in classification of invasive breast carcinoma: an NCI breast cancer family registry study. Mod. Pathol. 19, 195–207 (2006).

    Article  PubMed  Google Scholar 

  18. Rakha, E. A. et al. Prognostic significance of Nottingham histologic grade in invasive breast carcinoma. J. Clin. Oncol. 26, 3153–3158 (2008).

    Article  PubMed  Google Scholar 

  19. Habel, L. A. et al. A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients. Breast Cancer Res. 8, R25 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. van de Vijver, M. J. et al. A gene-expression signature as a predictor of survival in breast cancer. N. Engl. J. Med. 347, 1999–2009 (2002).

    Article  CAS  PubMed  Google Scholar 

  21. Sotiriou, C. et al. Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. J. Natl Cancer Inst. 98, 262–272 (2006).

    Article  CAS  PubMed  Google Scholar 

  22. Ellis, P. et al. in WHO Classification of Tumours. Pathology and Genetics of Tumours of the Breast and Female Genital Organs (eds Tavassoli, F. A. & Devilee, P) 13–59 (Lyon Press, Lyon, 2003).

    Google Scholar 

  23. Rakha, E. A. et al. Histologic grading is an independent prognostic factor in invasive lobular carcinoma of the breast. Breast Cancer Res. Treat 111, 121–127 (2008).

    Article  PubMed  Google Scholar 

  24. Wang, Y. et al. Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet 365, 671–679 (2005).

    Article  CAS  PubMed  Google Scholar 

  25. van 't Veer, L. J. et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature 415, 530–536 (2002).

    Article  CAS  PubMed  Google Scholar 

  26. Wirapati, P. et al. Meta-analysis of gene expression profiles in breast cancer: toward a unified understanding of breast cancer subtyping and prognosis signatures. Breast Cancer Res. 10, R65 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Geyer, F. C. & Reis-Filho, J. S. Microarray-based gene expression profiling as a clinical tool for breast cancer management: are we there yet? Int. J. Surg. Pathol. 17, 285–302 (2008).

    Article  Google Scholar 

  28. Farmer, P. et al. Identification of molecular apocrine breast tumours by microarray analysis. Oncogene 24, 4660–4671 (2005).

    Article  CAS  PubMed  Google Scholar 

  29. Abdullah-Sayani, A., Bueno- de-Mesquita, J. M. & van de Vijver, M. J. Technology Insight: tuning into the genetic orchestra using microarrays: limitations of DNA microarrays in clinical practice. Nat. Clin. Pract. Oncol. 3, 501–516 (2006).

    Article  CAS  PubMed  Google Scholar 

  30. Rosen, P. P. & Oberman, H. A. Tumors of the Mammary Gland (Armed Forces Institute of Pathology, Washington, DC, 1993).

    Google Scholar 

  31. Tavassoli, F. A. Classification of metaplastic carcinomas of the breast. Pathol. Annu. 27 (Pt 2), 89–119 (1992).

    PubMed  Google Scholar 

  32. Sakamoto, G. Histological classification of breast cancer [Japanese]. Gan No Rinsho (May Suppl.), 105–113 (1985).

  33. Sakamoto, G. Histological classification of breast cancer: 2 [Japanese]. Gan No Rinsho (Jan Suppl.), 197–204 (1986).

  34. Eusebi, V., Damiani, S., Ellis, I. O., Azzopardi, J. G. & Rosai J. Breast tumor resembling the tall cell variant of papillary thyroid carcinoma: report of 5 cases. Am. J. Surg. Pathol. 27, 1114–1118 (2003).

    Article  CAS  PubMed  Google Scholar 

  35. Asioli, S. et al. Polymorphous adenocarcinoma of the breast: report of three cases. Virchows Arch. 448, 29–34 (2006).

    Article  PubMed  Google Scholar 

  36. Collins, L. C. et al. Intracystic papillary carcinomas of the breast: a reevaluation using a panel of myoepithelial cell markers. Am. J. Surg. Pathol. 30, 1002–1007 (2006).

    Article  PubMed  Google Scholar 

  37. Mulligan, A. M. & O'Malley, F. P. Metastatic potential of encapsulated (intracystic) papillary carcinoma of the breast: a report of 2 cases with axillary lymph node micrometastases. Int. J. Surg. Pathol. 15, 143–147 (2007).

    Article  PubMed  Google Scholar 

  38. Leibl, S. & Moinfar, F. Mammary NOS-type sarcoma with CD10 expression: a rare entity with features of myoepithelial differentiation. Am. J. Surg. Pathol. 30, 450–456 (2006).

    Article  PubMed  Google Scholar 

  39. Wellings, S. R. & Jensen, H. M. On the origin and progression of ductal carcinoma in the human breast. J. Natl Cancer Inst. 50, 1111–1118 (1973).

    Article  CAS  PubMed  Google Scholar 

  40. Wellings, S. R., Jensen, H. M. & Marcum, R. G. An atlas of subgross pathology of the human breast with special reference to possible precancerous lesions. J. Natl Cancer Inst. 55, 231–273 (1975).

    CAS  PubMed  Google Scholar 

  41. Potti, A. et al. Genomic signatures to guide the use of chemotherapeutics. Nat. Med. 12, 1294–1300 (2006).

    Article  CAS  PubMed  Google Scholar 

  42. Peppercorn, J., Perou, C. M. & Carey, L. A. Molecular subtypes in breast cancer evaluation and management: divide and conquer. Cancer Invest. 26, 1–10 (2008).

    Article  CAS  PubMed  Google Scholar 

  43. Gusterson, B. Do 'basal-like' breast cancers really exist? Nat. Rev. Cancer 9, 128–134 (2009).

    Article  CAS  PubMed  Google Scholar 

  44. Moinfar, F. Is 'basal-like' carcinoma of the breast a distinct clinicopathological entity? A critical review with cautionary notes. Pathobiology 75, 119–131 (2008).

    Article  CAS  PubMed  Google Scholar 

  45. Rakha, E. A. et al. Morphological and immunophenotypic analysis of breast carcinomas with basal and myoepithelial differentiation. J. Pathol. 208, 495–506 (2006).

    Article  CAS  PubMed  Google Scholar 

  46. Livasy, C. A. et al. Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma. Mod. Pathol. 19, 264–271 (2006).

    Article  CAS  PubMed  Google Scholar 

  47. Rouzier, R. et al. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin. Cancer Res. 11, 5678–5685 (2005).

    Article  CAS  PubMed  Google Scholar 

  48. Parker, J. S. et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J. Clin. Oncol. 27, 1160–1167 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  49. Doane, A. S. et al. An estrogen receptor-negative breast cancer subset characterized by a hormonally regulated transcriptional program and response to androgen. Oncogene 25, 3994–4008 (2006).

    Article  CAS  PubMed  Google Scholar 

  50. Weigelt, B. et al. Refinement of breast cancer classification by molecular characterization of histological special types. J. Pathol. 216, 141–150 (2008).

    Article  CAS  PubMed  Google Scholar 

  51. Lien, H. C. et al. Molecular signatures of metaplastic carcinoma of the breast by large-scale transcriptional profiling: identification of genes potentially related to epithelial-mesenchymal transition. Oncogene 26, 7859–7871 (2007).

    Article  CAS  PubMed  Google Scholar 

  52. Bertucci, F. et al. Lobular and ductal carcinomas of the breast have distinct genomic and expression profiles. Oncogene 27, 5359–5372 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Zhao, H. et al. Different gene expression patterns in invasive lobular and ductal carcinomas of the breast. Mol. Biol. Cell 15, 2523–2536 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Korkola, J. E. et al. Differentiation of lobular versus ductal breast carcinomas by expression microarray analysis. Cancer Res. 63, 7167–7175 (2003).

    CAS  PubMed  Google Scholar 

  55. Weigelt, B., Kreike, B. & Reis-Filho, J. S. Metaplastic breast carcinomas are basal-like breast cancers: a genomic profiling analysis. Breast Cancer Res. Treat. 117, 273–280 (2008).

    Article  CAS  PubMed  Google Scholar 

  56. Bertucci, F. et al. Gene expression profiling shows medullary breast cancer is a subgroup of basal breast cancers. Cancer Res. 66, 4636–4644 (2006).

    Article  CAS  PubMed  Google Scholar 

  57. Jacquemier, J. et al. Typical medullary breast carcinomas have a basal/myoepithelial phenotype. J. Pathol. 207, 260–268 (2005).

    Article  CAS  PubMed  Google Scholar 

  58. Vincent-Salomon, A. et al. Identification of typical medullary breast carcinoma as a genomic sub-group of basal-like carcinomas, a heterogeneous new molecular entity. Breast Cancer Res. 9, R24 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Azoulay, S. et al. KIT is highly expressed in adenoid cystic carcinoma of the breast, a basal-like carcinoma associated with a favorable outcome. Mod. Pathol. 18, 1623–1631 (2005).

    Article  CAS  PubMed  Google Scholar 

  60. Reis-Filho, J. S. et al. Metaplastic breast carcinomas are basal-like tumours. Histopathology 49, 10–21 (2006).

    Article  CAS  PubMed  Google Scholar 

  61. Hayes, M. J., Thomas, D., Emmons, A., Giordano, T. J. & Kleer, C. G. Genetic changes of Wnt pathway genes are common events in metaplastic carcinomas of the breast. Clin. Cancer Res. 14, 4038–4044 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Stingl, J. & Caldas, C. Molecular heterogeneity of breast carcinomas and the cancer stem cell hypothesis. Nat. Rev. Cancer 7, 791–799 (2007).

    Article  CAS  PubMed  Google Scholar 

  63. Dontu, G., El-Ashry, D. & Wicha, M. S. Breast cancer, stem/progenitor cells and the estrogen receptor. Trends Endocrinol. Metab. 15, 193–197 (2004).

    Article  CAS  PubMed  Google Scholar 

  64. Behbod, F. & Rosen, J. M. Will cancer stem cells provide new therapeutic targets? Carcinogenesis 26, 703–711 (2005).

    Article  CAS  PubMed  Google Scholar 

  65. Hosey, A. M. et al. Molecular basis for estrogen receptor alpha deficiency in BRCA1-linked breast cancer. J. Natl Cancer Inst. 99, 1683–1694 (2007).

    Article  CAS  PubMed  Google Scholar 

  66. Liu, X. et al. Somatic loss of BRCA1 and p53 in mice induces mammary tumors with features of human BRCA1-mutated basal-like breast cancer. Proc. Natl Acad. Sci. USA 104, 12111–12116 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. McCarthy, A. et al. A mouse model of basal-like breast carcinoma with metaplastic elements. J. Pathol. 211, 389–398 (2007).

    Article  CAS  PubMed  Google Scholar 

  68. Polyak, K. Breast cancer: origins and evolution. J. Clin. Invest. 117, 3155–3163 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Tognon, C. et al. Expression of the ETV6-NTRK3 gene fusion as a primary event in human secretory breast carcinoma. Cancer Cell 2, 367–376 (2002).

    Article  CAS  PubMed  Google Scholar 

  70. Marchio, C. et al. Genomic and immunophenotypical characterization of pure micropapillary carcinomas of the breast. J. Pathol. 215, 398–410 (2008).

    Article  CAS  PubMed  Google Scholar 

  71. Letessier, A. et al. ETV6 gene rearrangements in invasive breast carcinoma. Genes Chromosomes Cancer 44, 103–108 (2005).

    Article  CAS  PubMed  Google Scholar 

  72. Makretsov, N. et al. A fluorescence in situ hybridization study of ETV6-NTRK3 fusion gene in secretory breast carcinoma. Genes Chromosomes Cancer 40, 152–157 (2004).

    Article  CAS  PubMed  Google Scholar 

  73. Reis-Filho, J. S. et al. Is acinic cell carcinoma a variant of secretory carcinoma? A FISH study using ETV6 'split apart' probes. Histopathology 52, 840–846 (2008).

    Article  CAS  PubMed  Google Scholar 

  74. Nassar, H. Carcinomas with micropapillary morphology: clinical significance and current concepts. Adv. Anat. Pathol. 11, 297–303 (2004).

    Article  PubMed  Google Scholar 

  75. Thor, A. D. et al. Invasive micropapillary carcinoma of the breast is associated with chromosome 8 abnormalities detected by comparative genomic hybridization. Hum. Pathol. 33, 628–631 (2002).

    Article  CAS  PubMed  Google Scholar 

  76. Hanby, A. M. & Hughes, T. A. In situ and invasive lobular neoplasia of the breast. Histopathology 52, 58–66 (2008).

    Article  CAS  PubMed  Google Scholar 

  77. Mathieu, M. C. et al. The poor responsiveness of infiltrating lobular breast carcinomas to neoadjuvant chemotherapy can be explained by their biological profile. Eur. J. Cancer 40, 342–351 (2004).

    Article  PubMed  Google Scholar 

  78. Vos, C. B. et al. E-cadherin inactivation in lobular carcinoma in situ of the breast: an early event in tumorigenesis. Br. J. Cancer 76, 1131–1133 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Droufakou, S. et al. Multiple ways of silencing E-cadherin gene expression in lobular carcinoma of the breast. Int. J. Cancer 92, 404–408 (2001).

    Article  CAS  PubMed  Google Scholar 

  80. Sarrio, D. et al. Epigenetic and genetic alterations of APC and CDH1 genes in lobular breast cancer: relationships with abnormal E-cadherin and catenin expression and microsatellite instability. Int. J. Cancer 106, 208–215 (2003).

    Article  CAS  PubMed  Google Scholar 

  81. Derksen, P. W. et al. Somatic inactivation of E-cadherin and p53 in mice leads to metastatic lobular mammary carcinoma through induction of anoikis resistance and angiogenesis. Cancer Cell 10, 437–449 (2006).

    Article  CAS  PubMed  Google Scholar 

  82. Reis-Filho, J. S. et al. EGFR amplification and lack of activating mutations in metaplastic breast carcinomas. J. Pathol. 209, 445–453 (2006).

    Article  CAS  PubMed  Google Scholar 

  83. Leibl, S., Gogg-Kammerer, M., Sommersacher, A., Denk, H. & Moinfar, F. Metaplastic breast carcinomas: are they of myoepithelial differentiation? Immunohistochemical profile of the sarcomatoid subtype using novel myoepithelial markers. Am. J. Surg. Pathol. 29, 347–353 (2005).

    Article  PubMed  Google Scholar 

  84. Leibl, S. & Moinfar, F. Metaplastic breast carcinomas are negative for Her-2 but frequently express EGFR (Her-1): potential relevance to adjuvant treatment with EGFR tyrosine kinase inhibitors? J. Clin. Pathol. 58, 700–704 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Turner, N. C. et al. BRCA1 dysfunction in sporadic basal-like breast cancer. Oncogene 26, 2126–2132 (2007).

    Article  CAS  PubMed  Google Scholar 

  86. Turner, N. C. & Reis-Filho, J. S. Basal-like breast cancer and the BRCA1 phenotype. Oncogene 25, 5846–5853 (2006).

    Article  CAS  PubMed  Google Scholar 

  87. Lien, H. C. et al. p53 overexpression and mutation in metaplastic carcinoma of the breast: genetic evidence for a monoclonal origin of both the carcinomatous and the heterogeneous sarcomatous components. J. Pathol. 204, 131–139 (2004).

    Article  CAS  PubMed  Google Scholar 

  88. Simpson, P. T. et al. Columnar cell lesions of the breast: the missing link in breast cancer progression? A morphological and molecular analysis. Am. J. Surg. Pathol. 29, 734–746 (2005).

    Article  PubMed  Google Scholar 

  89. Abdel-Fatah, T. M. et al. 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. 31, 417–426 (2007).

    Article  PubMed  Google Scholar 

  90. Abdel-Fatah, T. M. et al. Morphologic and molecular evolutionary pathways of low nuclear grade invasive breast cancers and their putative precursor lesions: further evidence to support the concept of low nuclear grade breast neoplasia family. Am. J. Surg. Pathol. 32, 513–523 (2008).

    Article  PubMed  Google Scholar 

  91. Chin, K. et al. Genomic and transcriptional aberrations linked to breast cancer pathophysiologies. Cancer Cell 10, 529–541 (2006).

    Article  CAS  PubMed  Google Scholar 

  92. Natrajan, R. et al. Tiling path genomic profiling of grade 3 invasive ductal breast cancers. Clin. Cancer Res. 15, 2711–2722 (2009).

    Article  CAS  PubMed  Google Scholar 

  93. Marchio, C. et al. Mixed micropapillary-ductal carcinomas of the breast: a genomic and immunohistochemical analysis of morphologically distinct components. J. Pathol. 218, 301–315 (2009).

    Article  CAS  PubMed  Google Scholar 

  94. Slamon, D. J. et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235, 177–182 (1987).

    Article  CAS  PubMed  Google Scholar 

  95. Bernard-Pierrot, I. et al. Characterization of the recurrent 8p11–12 amplicon identifies PPAPDC1B, a phosphatase protein, as a new therapeutic target in breast cancer. Cancer Res. 68, 7165–7175 (2008).

    Article  CAS  PubMed  Google Scholar 

  96. Reis-Filho, J. S. et al. FGFR1 emerges as a potential therapeutic target for lobular breast carcinomas. Clin. Cancer Res. 12, 6652–6662 (2006).

    Article  CAS  PubMed  Google Scholar 

  97. Cuny, M. et al. Relating genotype and phenotype in breast cancer: an analysis of the prognostic significance of amplification at eight different genes or loci and of p53 mutations. Cancer Res. 60, 1077–1083 (2000).

    CAS  PubMed  Google Scholar 

  98. Elbauomy Elsheikh, S. et al. FGFR1 amplification in breast carcinomas: a chromogenic in situ hybridisation analysis. Breast Cancer Res. 9, R23 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Hennessy, B. T. et al. Biphasic metaplastic sarcomatoid carcinoma of the breast. Ann. Oncol. 17, 605–613 (2006).

    Article  CAS  PubMed  Google Scholar 

  100. Ashworth, A. A synthetic lethal therapeutic approach: poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair. J. Clin. Oncol. 26, 3785–3790 (2008).

    Article  CAS  PubMed  Google Scholar 

  101. Flagiello, D. et al. Highly recurrent der(1;16)(q10;p10) and other 16q arm alterations in lobular breast cancer. Genes Chromosomes Cancer 23, 300–306 (1998).

    Article  CAS  PubMed  Google Scholar 

  102. Calza, S. et al. Intrinsic molecular signature of breast cancer in a population-based cohort of 412 patients. Breast Cancer Res. 8, R34 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Fan, C. et al. Concordance among gene-expression-based predictors for breast cancer. N. Engl. J. Med. 355, 560–569 (2006).

    Article  CAS  PubMed  Google Scholar 

  104. Rody, A. et al. The erbB2+ cluster of the intrinsic gene set predicts tumor response of breast cancer patients receiving neoadjuvant chemotherapy with docetaxel, doxorubicin and cyclophosphamide within the GEPARTRIO trial. Breast 16, 235–240 (2007).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors are grateful to Felipe Geyer for his insightful comments and entertaining discussions about the actual morphological features of special types of breast cancer and Dr. Kay Savage for the excellent histological sections. This manuscript is dedicated to the late Dr. Hans Peterse, an outstanding diagnostic histopathologist and a good friend, and to Dr. David Page, Prof Vincenzo Eusebi, Prof Ian Ellis, Prof Christopher Elston, Dr. Paul Peter Rosen and Prof John Azzopardi, whose pioneering work paved the way for a modern breast cancer taxonomy. We apologize to those investigators whose work we could not cite due to space constraints.

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Correspondence to Jorge S. Reis-Filho.

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Weigelt, B., Reis-Filho, J. Histological and molecular types of breast cancer: is there a unifying taxonomy?. Nat Rev Clin Oncol 6, 718–730 (2009). https://doi.org/10.1038/nrclinonc.2009.166

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