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Histologic grading is an independent prognostic factor in invasive lobular carcinoma of the breast

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Abstract

Invasive lobular carcinoma (ILC) comprises approximately 5–15% of breast cancers and appears to have a distinct biology. As it is less common than invasive ductal carcinoma, few studies of large size have addressed the value of assessment of histologic grade in ILC. Methods: This study is based on a large and well-characterised consecutive series of breast cancer (4,987 cases), from a single institution, with a long-term follow-up to assess the prognostic value of routine assessment of histologic grade in ILC. Histologic grade and other clinicopathological data were available in 517 pure ILC cases. A panel of biomarkers was also available for 215 cases. Results: The majority of ILC was of classical and mixed lobular variants (89%). Most ILC cases were moderately differentiated (grade 2) tumours (76%), while a small proportion of tumours were either grade 1 or 3 tumours (12% each). There were positive associations between histologic grade and other clinicopathological variables of poor prognosis such as larger size, positive lymph node, vascular invasion, oestrogen receptor and androgen receptor negativity and p53 positivity. Multivariate analyses showed that histologic grade is an independent predictor of shorter breast cancer specific survival and disease free interval. Conclusion: Histologic grade of ILC, as assessed by the Nottingham grading system, provides a strong predictor of outcome in patients with invasive lobular carcinoma of the breast and should be provided routinely in pathology reports.

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References

  1. Bloom HJ, Richardson WW (1957) Histological grading and prognosis in breast cancer; a study of 1409 cases of which 359 have been followed for 15 years. Br J Cancer 11:359–377

    PubMed  CAS  Google Scholar 

  2. Elston CW, Ellis IO (1991) 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

    Article  PubMed  CAS  Google Scholar 

  3. Symmers WC (1998) Assessment of histological grade. systemic pathology. In: Elston CW, Ellis IO (eds) The Breast, vol. 13. Churchill Livingstone, Edinburgh, p 381

    Google Scholar 

  4. Pereira H, Pinder SE, Sibbering DM et al (1995) Pathological prognostic factors in breast cancer. IV: Should you be a typer or a grader? A comparative study of two histological prognostic features in operable breast carcinoma. Histopathology 27:219–226

    Article  PubMed  CAS  Google Scholar 

  5. Sundquist M, Thorstenson S, Brudin L et al (1999) Applying the Nottingham Prognostic Index to a Swedish breast cancer population. South East Swedish Breast Cancer Study Group. Breast Cancer Res Treat 53:1–8

    Article  PubMed  CAS  Google Scholar 

  6. Dalton LW, Page DL, Dupont WD (1994) Histologic grading of breast carcinoma. A reproducibility study. Cancer 73:2765–2770

    Article  PubMed  CAS  Google Scholar 

  7. Frierson HF Jr, Wolber RA, Berean KW et al (1995) Interobserver reproducibility of the Nottingham modification of the Bloom and Richardson histologic grading scheme for infiltrating ductal carcinoma. Am J Clin Pathol 103:195–198

    PubMed  Google Scholar 

  8. Robbins P, Pinder S, de Klerk N et al (1995) Histological grading of breast carcinomas: a study of interobserver agreement. Hum Pathol 26:873–879

    Article  PubMed  CAS  Google Scholar 

  9. Elston CW, Ellis IO, Pinder SE (1999) Pathological prognostic factors in breast cancer. Crit Rev Oncol Hematol 31:209–223

    Article  PubMed  CAS  Google Scholar 

  10. Balslev I, Axelsson CK, Zedeler K et al (1994) The Nottingham Prognostic Index applied to 9,149 patients from the studies of the Danish Breast Cancer Cooperative Group (DBCG). Breast Cancer Res Treat 32:281–290

    Article  PubMed  CAS  Google Scholar 

  11. D’Eredita G, Giardina C, Martellotta M et al (2001) Prognostic factors in breast cancer: the predictive value of the Nottingham Prognostic Index in patients with a long-term follow-up that were treated in a single institution. Eur J Cancer 37:591–596

    Article  PubMed  CAS  Google Scholar 

  12. Okugawa H, Yamamoto D, Uemura Y et al (2005) Prognostic factors in breast cancer: the value of the Nottingham Prognostic Index for patients treated in a single institution. Surg Today 35:907–911

    Article  PubMed  Google Scholar 

  13. Third Edition of the NHS Breast Screening Programme’s Guidelines for Pathology Reporting in Breast Cancer Screening and the 2nd edn., of The Royal College of Pathologists’ Minimum Dataset for Breast Cancer Histopathology. Pathology reporting of breast disease. Sheffield, January 2005. NHSBSP Pub. No 58

  14. European Commission (1996) In: de Wolf CJM, Perry NM (eds) European guidelines for quality assurance in mammography screening. Office for Official Publications of the European Communities, Luxembourg

  15. WHO classification of Tumours (2003) In: Tavassoli FA, Devilee P (eds) Pathology and genetics. Tumours of the breast and female genital organs. IARC press, Lyon

  16. Galea MH, Blamey RW, Elston CE et al (1992) The Nottingham Prognostic Index in primary breast cancer. Breast Cancer Res Treat 22:207–219

    Article  PubMed  CAS  Google Scholar 

  17. Hanrahan EO, Valero V, Gonzalez-Angulo AM et al (2006) Prognosis and management of patients with node-negative invasive breast carcinoma that is 1 cm or smaller in size (stage 1; T1a,bN0M0): a review of the literature. J Clin Oncol 24:2113–2122

    Article  PubMed  Google Scholar 

  18. Tavassoli F, Devilee P (2003) World health organization classification of tumours. In: Kleihues P, Sobin L (eds) Tumours of the breast and female genital organs. IARCPress

  19. Fitzgibbons PL, Page DL, Weaver D et al (2000) Prognostic factors in breast cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med 124:966–978

    PubMed  CAS  Google Scholar 

  20. Singletary SE, Allred C, Ashley P et al (2002) Revision of the American Joint Committee on Cancer staging system for breast cancer. J Clin Oncol 20:3628–3636

    Article  PubMed  Google Scholar 

  21. Sastre-Garau X, Jouve M, Asselain B et al (1996) Infiltrating lobular carcinoma of the breast. Clinicopathologic analysis of 975 cases with reference to data on conservative therapy and metastatic patterns. Cancer 77:113–120

    Article  PubMed  CAS  Google Scholar 

  22. Arpino G, Bardou VJ, Clark GM et al (2004) Infiltrating lobular carcinoma of the breast: tumor characteristics and clinical outcome. Breast Cancer Res 6:R149–R156

    Article  PubMed  Google Scholar 

  23. Martinez V, Azzopardi JG (1979) Invasive lobular carcinoma of the breast: incidence and variants. Histopathology 3:467–488

    Article  PubMed  CAS  Google Scholar 

  24. Borst MJ, Ingold JA (1993) Metastatic patterns of invasive lobular versus invasive ductal carcinoma of the breast. Surgery 114:637–641; discussion 641–642

    PubMed  CAS  Google Scholar 

  25. Talman ML, Jensen MB, Rank F (2007) Invasive lobular breast cancer. Prognostic significance of histological malignancy grading. Acta Oncol 46:803–809

    Article  PubMed  Google Scholar 

  26. Sinn HP, Kellerhoff NM, Kellerhoff R et al (1997) Subtyping and prognostic assessment of invasive lobular breast carcinoma. Pathologe 18:37–44

    Article  PubMed  CAS  Google Scholar 

  27. Moreno-Elola A, Aguilar A, Roman JM et al (1999) Prognostic factors in invasive lobular carcinoma of the breast: a multivariate analysis. A multicentre study after seventeen years of follow-up. Ann Chir Gynaecol 88:252–258

    PubMed  CAS  Google Scholar 

  28. Bane AL, Tjan S, Parkes RK et al (2005) Invasive lobular carcinoma: to grade or not to grade. Mod Pathol 18:621–628

    Article  PubMed  Google Scholar 

  29. Sinha PS, Bendall S, Bates T (2000) Does routine grading of invasive lobular cancer of the breast have the same prognostic significance as for ductal cancers? Eur J Surg Oncol 26:733–737

    Article  PubMed  CAS  Google Scholar 

  30. Ellis IO, Galea M, Broughton N et al (1992) 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

    Article  PubMed  CAS  Google Scholar 

  31. du Toit RS, Locker AP, Ellis IO et al (1989) Invasive lobular carcinomas of the breast—the prognosis of histopathological subtypes. Br J Cancer 60:605–609

    PubMed  CAS  Google Scholar 

  32. Pinder SE, Ellis IO, Galea M et al (1994) Pathological prognostic factors in breast cancer. III. Vascular invasion: relationship with recurrence and survival in a large study with long-term follow-up. Histopathology 24:41–47

    Article  PubMed  CAS  Google Scholar 

  33. Abd El-Rehim DM, Ball G, Pinder SE et al (2005) High-throughput protein expression analysis using tissue microarray technology of a large well-characterised series identifies biologically distinct classes of breast cancer confirming recent cDNA expression analyses. Int J Cancer 116:340–350

    Article  PubMed  CAS  Google Scholar 

  34. Rakha EA, El-Sayed ME, Green AR et al (2007) Prognostic markers in triple-negative breast cancer. Cancer 109:25–32

    Article  PubMed  CAS  Google Scholar 

  35. Rakha EA, Putti TC, Abd El-Rehim DM et al (2006) Morphological and immunophenotypic analysis of breast carcinomas with basal and myoepithelial differentiation. J Pathol 208:495–506

    Article  PubMed  CAS  Google Scholar 

  36. Abd El-Rehim DM, Pinder SE, Paish CE et al (2004) Expression of luminal and basal cytokeratins in human breast carcinoma. J Pathol 203:661–671

    Article  PubMed  Google Scholar 

  37. Abd El-Rehim DM, Pinder SE, Paish CE et al (2004) Expression and co-expression of the members of the epidermal growth factor receptor (EGFR) family in invasive breast carcinoma. Br J Cancer 91:1532–1542

    Article  PubMed  CAS  Google Scholar 

  38. Schumacher M, Schmoor C, Sauerbrei W et al (1993) The prognostic effect of histological tumor grade in node-negative breast cancer patients. Breast Cancer Res Treat 25:235–245

    Article  PubMed  CAS  Google Scholar 

  39. Davis BW, Gelber RD, Goldhirsch A et al (1986) Prognostic significance of tumor grade in clinical trials of adjuvant therapy for breast cancer with axillary lymph node metastasis. Cancer 58:2662–2670

    Article  PubMed  CAS  Google Scholar 

  40. Page DL (1997) Prognostic indicators in breast cancer and who needs them. Anat Pathol 2:35–52

    PubMed  CAS  Google Scholar 

  41. Roberts MM, Alexander FE, Anderson TJ et al (1990) Edinburgh trial of screening for breast cancer: mortality at 7 years. Lancet 335:241–246

    Article  PubMed  CAS  Google Scholar 

  42. Ladekarl M, Sorensen FB (1993) Prognostic, quantitative histopathologic variables in lobular carcinoma of the breast. Cancer 72:2602–2611

    Article  PubMed  CAS  Google Scholar 

  43. Mokbel K (2001) Grading of infiltrating lobular carcinoma. Eur J Surg Oncol 27:609–610

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest statement

None declared. This study was approved by Nottingham Research Ethics Committee 2 under the title of “Development of a molecular genetic classification of breast cancer”.

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Correspondence to Ian O. Ellis.

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Rakha, E.A., El-Sayed, M.E., Menon, S. et al. Histologic grading is an independent prognostic factor in invasive lobular carcinoma of the breast. Breast Cancer Res Treat 111, 121–127 (2008). https://doi.org/10.1007/s10549-007-9768-4

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  • DOI: https://doi.org/10.1007/s10549-007-9768-4

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