Morphological determining prognostic factors in infiltrating breast carcinomas distant metastases

Authors

  • Lissette Ruiz Jorge Hospital Clínico Quirúrgico Universitario "Arnaldo Milián Castro"
  • Milagros Alegret Rodríguez Centro Provincial de Higiene y Epidemiología, Villa Clara
  • Isidro Machado Puerto Instituto Valenciano de Oncología, Valencia
  • Antonio Llombart-Bosh Universidad de Valencia

Keywords:

infiltrating breast carcinoma, prognosis, distant metastasis, disease-free survival

Abstract

Introduction: Distant metastasis reduces the survival of patients with infiltrating breast carcinomas and it is necessary to detect determining prognostic factors in their appearance. Objective: to identify morphological prognostic factors with predictive capacity for distant metastasis. Methods: a prospective longitudinal observational study was conducted in a sample of 333 patients diagnosed with infiltrating breast carcinomas in a period of 16 years. Size and tumor volume, multicentricity, multifocality, lymph node status, extracapsular or periganglionar infiltration, Berg´s ganglionar levels, histological subtype and grade, border and tumor necrosis, inflammatory response, lymphatic vascular invasion, intraductal component and surgical resection margins, were the variables. Survival analysis was performed for all variables by the Kaplan-Meier method in relation to distant metastases and the Log-Rank test was applied, comparisons in the subgroups of each variable were established to identify possible predictors. Results: of a 333 total patients, 59 presented distant metastasis with a 14.49 years average of presentation. Periganglionar infiltration, (p<0.005) ganglionar status 3, involvement of Berg's ganglionar level III, tumor volume >125cm3, histological subtypes ductal-lobular infiltrating, epidermoid and apocrine metaplastic, histological grade 3 and its components mitotic count >22 mitoses in 10 higher increase areas and nuclear pleomorphism 3 were very significant, and (0.005≤p<0.05), lymphovascular invasion, T3 and necrosis were significant. Conclusions: the morphological prognostic factors that were the best predictors of distant disease-free survival, were ganglionar state, periganglionar infiltration, Berg´s ganglionar levels, tumor volume, histological subtype and grade.

Downloads

Download data is not yet available.

Author Biographies

Lissette Ruiz Jorge, Hospital Clínico Quirúrgico Universitario "Arnaldo Milián Castro"

Especialista de II Grado en Anatomía Patológica. Doctora en Ciencias Médicas. Profesora Auxiliar de la Universidad de Ciencias Médicas de Villa Clara.

Milagros Alegret Rodríguez, Centro Provincial de Higiene y Epidemiología, Villa Clara

Doctora en Ciencias de la Salud. Profesora Titular de la Universidad de Ciencias Médicas de Villa Clara.

Isidro Machado Puerto, Instituto Valenciano de Oncología, Valencia

Doctor en Ciencias Médicas. Médico Patólogo Adjunto. Instituto Valenciano de Oncología.

Antonio Llombart-Bosh, Universidad de Valencia

Doctor en Ciencias Médicas. Catedrático Emérito de la Facultad de Medicina, Universidad de Valencia.

References

1. Khanfir A, Lahiani F, Bouzguenda R, Ayedi I, Daoud J, Frikha M. Prognostic factors and survival in metastatic breast cancer: A single institution experience. Rep Pract Oncol Radiother [Internet]. 2013 Feb [citado 20 Oct 2013];18(3):127-132. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863182/

2. Lester SC. The breast. En: Kumar V, editor. Robbins and Cotran Pathology basis of disease.8th ed. Philadelphia: Elsevier; 2010.

3. Tazhibi M, Fayaz M, Mokarian F. Detection of prognostic factors in metastatic breast cancer. J Res Med Sci [Internet]. 2013 Abr [citado 20 Oct 2013];18(4):283–290. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3793372/

4. Soriano García JL, Rubio Hernández MC, López Soto MV. Programa integral para el control del cáncer en Cuba: cáncer de mama, guía práctica clínica en diagnóstico y tratamiento. La Habana: Ecimed; 2013.

5. González Ortega JM, Morales Wong MM, López Cuevas Z, Díaz Valdéz M. Factores pronósticos del cáncer de mama. Rev cubana Cir [Internet]. 2011 [citado 20 Oct 2013];50(1):130-138. Disponible en: http://scielo.sld.cu/pdf/cir/v50n1/cir13111.pdf

6. Ellis IO, Schnitt SJ, Sastre-Garau X, Bussolati G, Tavassoli FA, Eusebi V. Tumours of the breast. En: Tavassoli FA, Devilee P, editors. Pathology & Genetics. Tumours of the breast and female genital organs [Internet]. Lyon: OMS; 2013 [citado 20 Oct 2013]. p. 10-59. Disponible en: https://www.iarc.fr/en/publications/pdfs-online/pat-gen/bb4/BB4.pdf

7. Ruiz Jorge L, Alegret Rodríguez M, Llombart-Bosh A, Machado Puerto I, Ramos Valdez J. Factores pronósticos clínicos y morfológicos determinantes en la supervivencia global en los carcinomas mamarios infiltrantes. Evaluación del volumen tumoral. Acta Méd Centro [Internet]. 2014 [citado 19 Dic 2014];8(3):37-47. Disponible en: http://www.revactamedicacentro.sld.cu/index.php/amc/article/view/144/182

8. Galea MH, Blamey RW, Elston CE, Ellis IO. The Nottingham Prognostic Index in primary breast cancer. Breast Cancer Res Treat [Internet]. 1992 [citado 12 Nov 2013];22(3):207-19. Disponible en: http://www.ncbi.nlm.nih.gov/pubmed/1391987

9. Eredita GD, Giardina C, Martellota M, Natale T, Ferrarese F. Factores de pronóstico en cáncer de mama: valor predictivo del Índice Pronóstico de Nottingham en pacientes con seguimiento a largo plazo, tratadas en una única institución. Eur J Cancer (Ed. Española) [Internet]. 2001 [citado 22 Sep 2013];1:401-406. Disponible en: https://slidex.tips/download/european-journal-of-cancer-ed-espaola-2001-1-departamento-de-cirugia-general-uni

10. Fujii T, Yanagita Y, Fujisawa T, Hirakata T, Iijima M, Kuwano H. Implication of extracapsular invasion of sentinel lymph nodes in breast cancer: prediction of nonsentinel lymph node metastasis. World J Surg [Internet]. 2010 Mar [citado 20 Oct 2013];34(3):544-8. Disponible en: http://www.ncbi.nlm.nih.gov/pubmed/20066412

11. Vera Álvarez JJ. Factores pronóstico del cáncer de mama. Bol Oncol [Internet]. 2000 [citado 15 Abr 2013];13(1). Disponible en: http://www.boloncol.com/boletin-13/factores-pronostico-del-cancer-de-mama.html

12. Berg JW. The significance of axillary node levels in the study of breast carcinoma. Cancer [Internet]. 1955 Jul-Ago [citado 22 Sep 2013];8:[aprox. 3 p.]. Disponible en: http://onlinelibrary.wiley.com/doi/10.1002/1097-0142%281955%298:4%3C776::AID-CNCR2820080421%3E3.0.CO;2-B/pdf

13. Sinn HP, Kreipe H. A brief overview of the WHO classification of breast tumors, 4th edition, focusing on issues and updates from the 3rd edition. Breast Care (Basel) [Internet]. 2013 May [citado 20 Oct 2013];8(2):149-54. Disponible en: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683948/

14. Aparna S, Paruchuri LP, Banisaeed N, Dunnington G, Rao KA. The clinical behavior of mixed ductal/lobular carcinoma of the breast: a clinicopathologic analysis. World J Surg Oncol [Internet]. 2010 [citado 20 Oct 2012];8:51. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904770/

15. Zengel B, Yararbas U, Duran A, Uslu A, Elıyatkın N, Demırkıran MA, et al. Comparison of the clinic pathological features of invasive ductal, invasive lobular, and mixed (invasive ductal + invasive lobular) carcinoma of the breast. Breast Cancer [Internet]. 2015 Jul [citado 2 Sep 2015];22(4):374-81. Disponible en: https://www.ncbi.nlm.nih.gov/pubmed/23925582

16. Gultekin M, Eren G, Babacan T, Yildiz F, Altundag K, Guler N, et al. Metaplastic breast carcinoma: a heterogeneous disease. Asian Pac J Cancer Prev [Internet]. 2014 [citado 19 Dic 2014];15(6):2851-6. Disponible en: https://www.ncbi.nlm.nih.gov/pubmed/24761913

17. Toumi Z, Bullen C, Tang AC, Dalal N, Ellenbogen S. Metaplastic breast carcinoma: a case report and systematic review of the literature. Pathol Int [Internet]. 2011 Oct [citado 22 sep 2013];61(10):582-8. Disponible en: https://www.ncbi.nlm.nih.gov/pubmed/21951667

18. Schwartz TL, Mogal H, Papageorgiou C, Veerapong J, Hsueh EC. Metaplastic breast cancer: histologic characteristics, prognostic factors and systemic treatment strategies. Experiment Hematol Oncol [Internet]. 2013 [citado 25 Nov 2013];2:31. Disponible en: https://ehoonline.biomedcentral.com/track/pdf/10.1186/2162-3619-2-31

19. Lee H, Jung SY, Ro JY, Kwon Y, Sohn JH, Park IH, et al. Metaplastic breast cancer: clinicopathological features and its prognosis. J Clin Pathol [Internet]. 2012 May [citado 25 Sep 2013];65(5):441-6. Disponible en: https://www.ncbi.nlm.nih.gov/pubmed/22412048

20. Weigelt B, Kreike B, Reis-Filho JS. Metaplastic breast carcinomas are basal-like breast cancers: a genomic profiling analysis. Breast Cancer Res Treat [Internet]. 2009 Sep [citado 25 Sep 2013];117(2):273-80. Disponible en: https://www.ncbi.nlm.nih.gov/pubmed/18815879

21. Dellapasqua S, Maisonneuve P, Viale G, Pruneri G, Mazzarol G, Ghisini R, et al. Immunohistochemically defined subtypes and outcome of apocrine breast cancer. Clin Breast Cancer [Internet]. 2013 Apr [citado 25 Sep 2013];13(2):95-102. Disponible en: https://www.ncbi.nlm.nih.gov/pubmed/23245877

22. Volpi A, Bacci F, Paradiso A, Saragoni L, Scarpi E, Ricci M, et al. Prognostic relevance of histological grade and its components in node-negative breast cancer patients. Modern Pathology [Internet]. 2004 [citado 25 Sep 2013];17:1038–1044. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904770/

23. Desmedt C, Giobbie-Hurder A, Neven P, Paridaens R, Christiaens MR, Smeets A, et al. The Gene expression Grade Index: a potential predictor of relapse for endocrine-treated breast cancer patients in the BIG 1–98 trial. BMC Medical Genomics [Internet]. 2009 [citado 18 Jun 2012];2(40):[aprox. 14 p]. Disponible en: http://www.biomedcentral.com/1755-8794/2/40

24. Ignatiadis M, Desmedt C. Predicting risk of breast cancer recurrence using gene-expression profiling. Pharmacogenomics [Internet]. 2007 [citado 25 Oct 2013];8(1):101-111. Disponible en: http://www.futuremedicine.com/doi/abs/10.2217/14622416.8.1.101

25. Ignatiadis M, Sotiriou C. Understanding the Molecular Basis of Histologic Grade. Pathobiology [Internet]. 2008 [citado 20 Oct 2013];75(2):104-111. Disponible en: http://www.online.karger.com/Article/FullText/123848

26. Sotiriou C, Wirapati P, Loi S, Harris A, Fox S, Smeds J, et al. Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. J Natl Cancer Inst [Internet]. 2006 Feb [citado 20 Sep 2013];98(4):262-72. Disponible en: http://jnci.oxfordjournals.org/content/98/4/262.full.pdf+html

27. Meyer JS, Alvarez C, Milikowski C, Olson N, Russo I, Russo J, et al. Breast carcinoma malignancy grading by Bloom–Richardson system vs proliferation index: reproducibility of grade and advantages of proliferation index. Mod Pathol [Internet]. 2005 Aug [citado 22 Sep 2013];18(1):1067-78. Disponible en: http://www.ncbi.nlm.nih.gov/pubmed/15920556

28. Rakha EA, Reis-Filho JS, Baehner F, Dabbs DJ, Decker T, Eusebi V, et al. Breast cancer prognostic classification in the molecular era: the role of histological grade. Breast Cancer Res [Internet]. 2010 [citado 3 May 2013];12(4):207. Disponible en: http://www.ncbi.nlm.nih.gov/pubmed/20804570

29. van Diest PJ, van der Wall E, Baak JP. Prognostic value of proliferation in invasive breast cancer: a review. J ClinPathol [Internet]. 2004 [citado 22 Sep 2013];57(7):675-81. Disponible en: http://www.ncbi.nlm.nih.gov/pubmed/15220356

30. El All HA, Ismail E, Abbas M, Ouf K. MIB-1 index, S-phase fraction, mitotic figure count, and SBR histologic grading in invasive breast carcinoma: a comparative study. Breast J [Internet]. 2001 [citado 22 Sep 2013];7(2):[aprox. 5 p.]. Disponible en: http://www.ncbi.nlm.nih.gov/pubmed/11328317

31. van de Vijver MJ. Molecular tests as prognostic factors in breast cancer. Virchows Arch [Internet]. 2014 Mar [citado 19 Dic 2014];464:283–291. Disponible en: http://www.ncbi.nlm.nih.gov/pubmed/24487789

32. Italian Network for Quality Assurance of Tumour Biomarkers (INQAT) Group. Quality control for histological grading in breast cancer: an italian experience. Pathologica [Internet]. 2005 [citado 22 Sep 2013];97:1-6. Disponible en: http://www.siapec.it/content/file/972/01%20verderio.pdf

33. Bussolati G, Marchiò C, Gaetano L, Lupo R, Sapino A. Pleomorphism of the nuclear envelope in breast cancer: a new approach to an old problem. J Cell Mol Med [Internet]. 2008 [citado 22 Sep 2013];12(1):[aprox. 9 p.]. Disponible en: http://www.ncbi.nlm.nih.gov/pubmed/18053086

34. Ichizawa N, Fukutomi T, Iwamoto E, Akashi-Tanaka S. Long-term results of T1a, T1b and T1c invasive breast carcinoma in japanese women: validation of the UICC T1 sudgroup classification. Jpn J Clin Oncol [Internet]. 2002 [citado 22 Sep 2013];32(3):108-115. Disponible en: https://www.ncbi.nlm.nih.gov/pubmed/11956306

35. Gujam FJ, Going JJ, Edwards J, Mohammed ZM, McMillan DC. The role of lymphatic and blood vessel invasion in predicting survival and methods of detection in patients with primary operable breast cancer. Crit Rev Oncol Hematol [Internet]. 2014 Feb [citado 19 Dic 2014];89(2):231-41. Disponible en: http://www.croh-online.com/article/S1040-8428%2813%2900191-1/abstract

36. Yoshihara E, Smeets A, Laenen A, Reynders A, Soens J, Van Ongeval C, et al. Predictors of axillary lymph node metastases in early breast cancer and their applicability in clinical practice. Breast [Internet]. 2013 Jun [citado 22 Sep 2013];22(3):[aprox. 4 p.]. Disponible en: http://www.ncbi.nlm.nih.gov/pubmed/23022046

37. Rakha E, Reis-Filho JS. Basal-like breast carcinoma: from expression profiling to routine practice. Arch Pathol Lab Med [Internet]. 2009 Jun [citado 3 Ago 2013];133(6):860-8. Disponible en: https://www.ncbi.nlm.nih.gov/pubmed/19492878

38. Liu H, Fan QH, Li X, Liu GZ. Clinicopathologic features and prognostic significance of basal-like breast cancer. Zhonghua Bing Li Xue Za Zhi [Internet]. 2009 May [citado 3 Ago 2013];38(5):316-22. Disponible en: https://www.ncbi.nlm.nih.gov/pubmed/19575874

39. Nassar A, Sussman ZM, Lawson D, Cohen C. Inference of the basal epithelial phenotype in breast carcinoma from differential marker expression, using tissue microarrays in triple negative breast cancer and women younger than 35. Breast J [Internet]. 2012 Sep [citado 3 Ago 2013;18(5):399-405. Disponible en: https://www.ncbi.nlm.nih.gov/pubmed/22882580

40. Engels CC, Ruberta F, de Kruijf EM, van Pelt GW, Smit VT, Liefers GJ, et al. The prognostic value of apoptotic and proliferative markers in breast cancer. Breast Cancer Res Treat [Internet]. 2013 Nov [citado 19 Dic 2014];142(2):323-39. Disponible en: http://www.ncbi.nlm.nih.gov/pubmed/24194179

41. Lipponen P. Apoptosis in breast cancer: relationship with other pathological parameters. Endocr Related Cancer [Internet]. 1999 Mar [citado 19 Dic 2014];6(1):13-6. Disponible en: https://pdfs.semanticscholar.org/af3a/190772e9a931bc16a98189bcf415133a1a0d.pdf

42. Zaha DC, Lazăr E. Molecular characterization of apoptosis by the immunohistochemical evaluation of Bcl-2 in breast cancer. Rom J Morphol Embryol [Internet]. 2012 [citado 19 Dic 2014];53(1):155-60. Disponible en: https://www.ncbi.nlm.nih.gov/pubmed/22395515

Published

2018-07-02

How to Cite

1.
Ruiz Jorge L, Alegret Rodríguez M, Machado Puerto I, Llombart-Bosh A. Morphological determining prognostic factors in infiltrating breast carcinomas distant metastases. Acta Méd Centro [Internet]. 2018 Jul. 2 [cited 2025 Jun. 28];12(3):250-61. Available from: https://revactamedicacentro.sld.cu/index.php/amc/article/view/912

Issue

Section

Original Articles