Pathology & Oncology Research

, Volume 18, Issue 4, pp 823–831 | Cite as

Significance of Histomorphology of Early Triple-Negative Breast Cancer

  • Gábor RubovszkyEmail author
  • Zsolt Horváth
  • Erika Tóth
  • István Láng
  • Miklós Kásler


Triple-negative breast cancer (TNBC) is a heterogeneous disease. Possibly genetic characterisation provides the most appropriate information on tumour biology and prognosis, but it is only limitedly available in clinical practice. The aim of this investigation was to explore what additional prognostic information could be gained from detailed histomorphologic report. Patients and method: patients were selected retrospectively operated from 2005 to 2009 in one institution and charts were revised. Beyond age, tumour and nodal status, histologic grade and therapy, the additional pathologic characteristics were also involved in analysis: necrosis, lymphocytic infiltration, peritumoural vascular invasion (PVI), perineural invasion, DCIS extent and grade, perinodal spread, mitotic activity index (MAI). Results: 295 early TNBC were involved. In univariate survival analysis with a mean follow-up of 3.57 years the tumour size, the nodal status, type of operation (conservation or mastectomy), irradiation, PVI and perinodal spread proved to be significantly connected with both disease free survival (DFS) and breast cancer specific overall survival (BSOS), and necrosis and chemotherapy with BSOS. Necrosis analysed together with lymphocytic infiltrate showed greater predicting power. In multivariate analysis nodal metastasis, necrosis positive/lymphacytic infiltration negative status and lack of irradiation has significant negative impact on DFS (p = <0.0001 HR:1.98 [1.4–2.77], p = <0.017 HR:2.1 [1.1–3.8], p = <0.001 HR:0.25 [0.11–0.57], respectively) and BSOS (p = <0.0001 HR:2.47 [1.8–3.4], p = <0.017 HR:3.7 [1.6–8.2], p = <0.0017 HR:0.24 [0.1–0.58], respectively). For DFS perivascular invasion also showed significant effect (p = <0.042 HR:2.5 [1.0–6.0]). Nodal status was the strongest prognostic parameter but other histomorphologic parameters can be used for prognosis prediction.


Triple-negative breast cancer Vascular invasion Necrosis Irradiation 



We are grateful to statistician Istvan Gaudi for his unlimited support in statistical analysis and to Monika Nagy and Tibor Radovics for their help in data acquisition.


  1. 1.
    Rakha EA, El-Sayed ME, Green AR et al (2007) Prognostic markers in triple-negative breast cancer. Cancer 109:25–32PubMedCrossRefGoogle Scholar
  2. 2.
    Sorlie T, Perou CM, Tibshirani R et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implication. Proc Natl Acad Sci U S A 98:10869–10874PubMedCrossRefGoogle Scholar
  3. 3.
    Kreike B, van Kouwenhove M, van de Vijver MJ et al (2007) Gene expression profiling and histopathological characterization of triple-negative /basal-like breast carcinomas. Breast Cancer Res 9:R65PubMedCrossRefGoogle Scholar
  4. 4.
    Lehmann BD, Bauer JA, Chen X, Sanders ME, Bapsi Chakravarthy A, Shyr Yu, Pietenpol JA (2011) Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest 121:2750–2767PubMedCrossRefGoogle Scholar
  5. 5.
    Teschendorff AE, Caldas C (2008) A robust classifier of high predictive value to identify good prognosis patients in ER-negative breast cancer. Breast Cancer Res 10:R73PubMedCrossRefGoogle Scholar
  6. 6.
    Yerushalmi R, Hayes MM, Gelmon KA (2009) Breast carcinoma–rare types: review of the literature. Ann Oncol 20:1763–1770PubMedCrossRefGoogle Scholar
  7. 7.
    Mohammed RA, Ellis IO, Lee AH, Martin SG (2009) Vascular invasion in breast cancer; an overview of recent prognostic developments and molecular pathophysiological mechanisms. Histopathology 55:1–9PubMedCrossRefGoogle Scholar
  8. 8.
    Viale G, Giobbie-Hurder A, Gusterson BA, Maiorano E, Mastropasqua MG, Sonzogni A, Mallon E, Colleoni M, Castiglione-Gertsch M, Regan MM, Price KN, Brown RW, Golouh R, Crivellari D, Karlsson P, Ohlschlegel C, Gelber RD, Goldhirsch A, Coates AS (2010) Adverse prognostic value of peritumoral vascular invasion: is it abrogated by adequate endocrine adjuvant therapy? Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy for early breast cancer. Ann Oncol 21:245–254PubMedCrossRefGoogle Scholar
  9. 9.
    Pinder SE, Ellis IO, Galea M, O’Rouke S, Blamey RW, Elston CW (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 24:41–47PubMedCrossRefGoogle Scholar
  10. 10.
    Sabatier R, Jacquemier J, Bertucci F, Esterni B, Finetti P, Azario F, Birnbaum D, Viens P, Gonçalves A, Extra JM (2011) Peritumoural vascular invasion: a major determinant of triple-negative breast cancer outcome. Eur J Cancer 47:1537–1545PubMedCrossRefGoogle Scholar
  11. 11.
    Lende TH, Janssen EA, Gudlaugsson E, Voorhorst F, Smaaland R, van Diest P, Søiland H, Baak JP (2011) In patients younger than age 55 years with lymph node-negative breast cancer, proliferation by mitotic activity index is prognostically superior to adjuvant! J Clin Oncol 29:852–858PubMedCrossRefGoogle Scholar
  12. 12.
    Galea MH, Blamey RW, Elston CE, Ellis IO (1992) The Nottingham Prognostic Index in primary breast cancer. Breast Cancer Res Treat 22:207–219PubMedCrossRefGoogle Scholar
  13. 13.
    Choi YL, Oh E, Park S, Kim Y, Park YH, Song K, Cho EY, Hong YC, Choi JS, Lee JE, Kim JH, Nam SJ, Im YH, Yang JH, Shin YK (2010) Triple-negative, basal-like, and quintuple-negative breast cancers: better prediction model for survival. BMC Cancer 10:507PubMedCrossRefGoogle Scholar
  14. 14.
    Schiffman SC, McMasters KM, Scoggins CR, Martin RC, Chagpar AB (2011) Lymph node ratio: a proposed refinement of current axillary staging in breast cancer patients. J Am Coll Surg 213:45–52PubMedCrossRefGoogle Scholar
  15. 15.
    Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF (2007) American Society of Clinical Oncology; College of American Pathologists. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 25:118–145PubMedCrossRefGoogle Scholar
  16. 16.
    Bidard FC, Conforti R, Boulet T, Michiels S, Delaloge S, André F (2007) Does triple-negative phenotype accurately identify basal-like tumour? An immunohistochemical analysis based on 143 ‘triple-negative’ breast cancers. Ann Oncol 18:1285–1286PubMedCrossRefGoogle Scholar
  17. 17.
    Lin C, Chien SY, Chen LS, Kuo SJ, Chang TW, Chen DR (2009) Triple negative breast carcinoma is a prognostic factor in Taiwanese women. BMC Cancer 9:192PubMedCrossRefGoogle Scholar
  18. 18.
    Liu ZB, Liu GY, Yang WT et al (2008) Triple-negative breast cancer types exhibit a distinct poor clinical characteristic in lymph node-negative Chinese patients. Oncol Rep 20:987–994PubMedGoogle Scholar
  19. 19.
    Bauer KR, Brown M, Cress RD et al (2007) Descripitive analysis of estrogen receptor (ER)-negative, progesteron receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population based study from the California Cancer Registry. Cancer 109:1721–1728PubMedCrossRefGoogle Scholar
  20. 20.
    Onitilio AA, Engel JM, Greenlee RT et al (2009) Breast cancer subtypes based on ER/PR and Her2 expression: comparison of clinicopathologic features and survival. Clin Med Res 7:4–13CrossRefGoogle Scholar
  21. 21.
    Carey LA, Perou CM, Livasy CA et al (2008) Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA 295:2492–2502CrossRefGoogle Scholar
  22. 22.
    Spitale A, Mazzola P, Soldini D et al (2009) Breast cancer classification according to immunohistochemical markers: clinicipathologic features and short-term survival analysis in a population-based study from the South of Switzerland. Ann Oncol 20:628–635PubMedCrossRefGoogle Scholar
  23. 23.
    Nofech-Mozes S, Trudeau M, Kahn HK, Dent R, Rawlinson E, Sun P, Narod SA, Hanna WM (2009) Patterns of recurrence in the basal and non-basal subtypes of triple-negative breast cancers. Breast Cancer Res Treat 118:131–137PubMedCrossRefGoogle Scholar
  24. 24.
    Mohammed RA, Ellis IO, Mahmmod AM, Hawkes EC, Green AR, Rakha EA, Martin SG (2011) Lymphatic and blood vessels in basal and triple-negative breast cancers: characteristics and prognostic significance. Mod Pathol 24:774–785PubMedCrossRefGoogle Scholar
  25. 25.
    Linderholm BK, Hellborg H, Johansson U, Elmberger G, Skoog L, Lehtiö J, Lewensohn R (2009) Significantly higher levels of vascular endothelial growth factor (VEGF) and shorter survival times for patients with primary operable triple-negative breast cancer. Ann Oncol 20:1639–1646PubMedCrossRefGoogle Scholar
  26. 26.
    Liu HT, Ma R, Yang QF, Du G, Zhang CJ (2009) Lymphangiogenic characteristics of triple negativity in node-negative breast cancer. Int J Surg Pathol 17:426–431PubMedCrossRefGoogle Scholar
  27. 27.
    Colleoni M, Rotmensz N, Maisonneuve P, Sonzogni A, Pruneri G, Casadio C, Luini A, Veronesi P, Intra M, Galimberti V, Torrisi R, Andrighetto S, Ghisini R, Goldhirsch A, Viale G (2007) Prognostic role of the extent of peritumoral vascular invasion in operable breast cancer. Ann Oncol 18:1632–1640PubMedCrossRefGoogle Scholar
  28. 28.
    Oven Ustaalioglu BB, Bilici A, Kefeli U, Seker M, Yildirim E, Salepci T, Oncel M, Kement M, Gumus M (2010) Does the metastatic lymph node ratio influence the disease-free survival of patients with breast cancer: single-center experiences. Oncology 79:105–111PubMedCrossRefGoogle Scholar
  29. 29.
    Mersin H, Yildirim E, Berberoglu U, Gulben K (2009) Triple negative phenotype and N-ratio are important for prognosis in patients with stage IIIB non-inflammatory breast carcinoma. J Surg Oncol 100:681–687PubMedCrossRefGoogle Scholar
  30. 30.
    Viale G, Regan MM, Maiorano E, Mastropasqua MG, Dell’Orto P, Rasmussen BB, Raffoul J, Neven P, Orosz Z, Braye S, Ohlschlegel C, Thürlimann B, Gelber RD, Castiglione-Gertsch M, Price KN, Goldhirsch A, Gusterson BA, Coates AS (2007) Prognostic and predictive value of centrally reviewed expression of estrogen and progesterone receptors in a randomized trial comparing letrozole and tamoxifen adjuvant therapy for postmenopausal early breast cancer: BIG 1–98. J Clin Oncol 25:3846–3852PubMedCrossRefGoogle Scholar
  31. 31.
    Stuart-Harris R, Caldas C, Pinder SE, Pharoah P (2008) Proliferation markers and survival in early breast cancer: a systematic review and meta-analysis of 85 studies in 32,825 patients. Breast 17:323–334PubMedCrossRefGoogle Scholar
  32. 32.
    Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, Hicks DG, Lester S, Love R, Mangu PB, McShane L, Miller K, Osborne CK, Paik S, Perlmutter J, Rhodes A, Sasano H, Schwartz JN, Sweep FC, Taube S, Torlakovic EE, Valenstein P, Viale G, Visscher D, Wheeler T, Williams RB, Wittliff JL, Wolff AC (2010) American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol 28:2784–2795PubMedCrossRefGoogle Scholar

Copyright information

© Arányi Lajos Foundation 2012

Authors and Affiliations

  • Gábor Rubovszky
    • 1
    Email author
  • Zsolt Horváth
    • 1
  • Erika Tóth
    • 1
  • István Láng
    • 1
  • Miklós Kásler
    • 1
  1. 1.National Institute of OncologyBudapestHungary

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