The last part of our discussion, on the analyzed biomarkers, focuses on HER2, the transmembrane glycoprotein with intracellular tyrosine kinase activity belonging to the EGFR family, which becomes active by homo- and heterodimerization, by which HER2-HER3 plays an important role in carcinogenesis through the activation of the PI3K/protein kinase B/mammalian target of the rapamycin pathway.83,84 HER2 overexpression has been found in ~13%–23% of breast cancers and is associated with poor survival.85 According to the 2015 St Gallen recommendations and ASCO and CAP guidelines, the HER2 IHC staining score in the triple-negative phenotype could be 0 or 1+ or equivocal (2+) and negative according to the ISH test. The ERBB2 gene copy is closely associated with HER2 protein expression, but studies show that only around 20% of tumors with positive immunostaining in ≤50% of cells showed gene amplification compared with 85.7% of tumors presenting positive staining in >50% of cells.7,10,11,86

Therefore, it is highly probable that the triple-negative phenotype bearing an amplified ERBB2 gene would not have the same clinical behavior as a tumor without staining or with incomplete staining in <10% of the tumor cells. In breast cancer, HER2 overexpression is an independent negative prognostic factor directly correlated with tumor grade and lymph node involvement and inversely correlated with ER expression.87 Not many studies addressed the question of clinical relevance of HER2 score in nonmetastatic triple negative breast cancer population and the results are inconclusive. In 119 non-metastatic TNBCs, patients with a HER2-neu score of 0 had a significantly poorer outcome in terms of DFS and OS compared with those with a HER2 score of 1 or 2 (P=0.0021, P=0.0105).88 In our previous analysis of 47 patients with early-stage TNBC, we found the median EFS to be shorter in the HER2-positive, ISH-negative cases (29.2 months) than in the HER2-negative ones (31.8 months), without reaching significance (P=0.9).89

In our triple-negative patients, HER2 expression was marginally correlated with lymphovascular invasion (P=0.072) and significantly with histopathological type (P=0.001). In relapsed patients, some differences existed in HER2 expression: 88.9% (16 patients) were negative and 11.1% had weak expression (P=0.559) with no significant differences between the mean EFS of the subgroups.

Continue Reading

Of the biomarkers examined in the present study, only EGFR was found to be significantly directly correlated with the triple-negative phenotype. In the literature, EGFR and CK5/6 co-expression are described in approximately half of triple-negative tumors, as they stand for the poor prognostic basal-like subtype.34,90 Regarding less specific biomarkers, TNBC appeared to be associated with p53 expression and high Ki67 levels in >50% of cases.91

As for outcomes, the only biomarker whose expression was inversely correlated with relapse in our specific population was that of CK5/6. Patients considered to be CK5/6 negative had five times higher risk of relapse than those displaying biomarker expression. Lastly, for our target population, we proposed a prognostic score based on CK5/6 and E-cad expression, but the differences between the identified subgroups did not reach statistical significance. Among previous scores assessing roughly the same types of IHC biomarkers in non-metastatic TNBC patients is the study of Kashiwagi et al, who evaluated the prognostic role of E-cad and Ki67 in 138 triple-negative patients undergoing adjuvant chemotherapy. The combination of E-cad negative and high Ki67 was associated with worse OS (P<0.001).92 In another study of E-cad, AR, and Ki67 expression in a small cohort (N=45) of primary operable TNBC patients, AR-negative and Ki67-positive patients had a significantly poorer OS (P=0.0202).49 In 102 Japanese patients with invasive TNBC who underwent primary surgery, analysis of the prognostic role of histological factors, such as pathological tumor size and nodal status, along with basal-like specific marker expression (EGFR, CK5/6, CK14, and CK35), led to the creation of three leader scores, of which the three groups of patients had statistically different risks of relapse and breast cancer-specific deaths, respectively.93 In a recent analysis of 99 cases of TNBC, CK5/6 expression was inversely correlated with AR and Ki67 levels, and it was associated with a better outcome than for CK5/6-negative patients (HR =0.39; P=0.02). Moreover, E-cad expression was found to be an independent favorable prognostic biomarker (P=0.05).56

In agreement with these results, the population that expressed both biomarkers in our study displayed the longest EFS, whereas those that did not express any biomarker showed the poorest outcomes. This finding might be explained by the absence of differences in CK5/6 expression in triple-negative compared with non-triple-negative patients as well as because there is no established cutoff for CK5/6 positivity. Furthermore, in several studies, the threshold was 1%, whereas our cutoff of 10% was fixed by the institutional internal laboratory. The participation of E-cad in our score as a good prognostic biomarker is as expected, as the absence of expression was found to be associated with poorer outcomes in other studies,32 seemingly correlated with the basal-like subtype.49


Given the published research, our preliminary analyses were designed to investigate a plethora of biomarkers correlated with various clinical and histopathological prognostic factors, but whose correlations with relapse or survival without relapse had not yet been confirmed. Due to the small number of TNBC patients and even smaller number of those patients tested for each biomarker, the results in our study were often statistically insignificant.

Other teams have assessed several scores to identify patients with good prognoses within this population, but none of them has yet been validated. Each of our score component biomarkers (CK5/6 and E-cad) has been assessed as a constituent of such scores, but to our knowledge, these two have not been assessed solely together.

Other limitations of our study include the lack of standardization for the IHC assessment of biomarkers, other than the assessment of hormone receptors or HER2, and lack of guidelines for interpretation and reproducibility, which leads to discordant results.

We will add inferential statistical tests to identify other factors that might be included in our score. The final analysis will also contain the application of the score in borderline tumors, such as ER 1%–10%, PR 1%–10%, and non-expressing HER2 population, to identify the subgroups of very bad prognoses.


We would like to thank Mr Everardo D Saad for his written contribution and Mr Sorin S Opris for his assistance in preparing the article.


The authors report no conflicts of interest in this work.

Silvia Mihaela Ilie,1 Xenia Elena Bacinschi,1,2 Inga Botnariuc,2 Rodica Maricela Anghel1,2

1University of Medicine and Pharmacy “Carol Davila,” Bucharest, Romania; 2Department of Oncology-Radiotherapy, Institute of Oncology “Prof Dr Alexandru Trestioreanu,” Bucharest, Romania  


1. Forouzanfar MH, Foreman KJ, Delossantos AM, et al. Breast and cervical cancer in 187 countries between 1980 and 2010: a systematic analysis. Lancet. 2011;378(9801):1461–1484.

2. Prat A, Perou CM. Deconstructing the molecular portraits of breast cancer. Mol Oncol. 2011;5(1):5–23.

3. Sørlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001;98(19):10869–10874.

4. Parker JS, Mullins M, Cheang MC, et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol. 2009;27(8):1160–1167.

5. Bastien RR, Rodríguez-Lescure Á, Ebbert MT, et al. PAM50 breast cancer subtyping by RT-qPCR and concordance with standard clinical molecular markers. BMC Med Genomics. 2012;5:44.

6. Voduc KD, Cheang MC, Tyldesley S, Gelmon K, Nielsen TO, Kennecke H. Breast cancer subtypes and the risk of local and regional relapse.  J Clin Oncol. 2010;28(10):1684–1691.

7. Coates AS, Winer EP, Goldhirsch A, et al; American Society of Clinical Oncology; College of American Pathologists. Tailoring therapies—improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015. Ann Oncol. 2015;26(8):1533–1546.

8. Foulkes WD, Smith IE, Reis-Filho JS. Triple-Negative Breast Cancer. N Engl J Med. 2010;363(20):1938–1948.

9. Hammond ME, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. Arch Pathol Lab Med. 2010;134(6):907–922.

10. Wolff AC, Hammond ME, Schwartz JN, et al; 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. 2007;25(1):118–145.

11. Irvin WJ Jr, Carey LA. What is triple-negative breast cancer? Eur J Cancer. 2008;44(18):2799–2805.

12. Lin NU, Vanderplas A, Hughes ME, et al. Clinicopathologic features, patterns of recurrence, and survival among women with triple-negative breast cancer in the National Comprehensive Cancer Network. Cancer. 2012;118(22):5463–5472.

13. Smid M, Wang Y, Zhang Y, et al. Subtypes of breast cancer show preferential site of relapse. Cancer Res. 2008;68(9):3108–3114.

14. Dent R, Trudeau M, Pritchard KI, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007;13(15 Pt 1):4429–4434.

15. Kaplan HG, Malmgren JA, Atwood M. T1N0 triple negative breast cancer: risk of recurrence and adjuvant chemotherapy. Breast J. 2009;15(5):454–460.

16. Podo F, Buydens LM, Degani H, et al; FEMME Consortium. Triple-negative breast cancer: present challenges and new perspectives. Mol Oncol. 2010;4(3):209–229.

17. Alvarez RH, Valero V, Hortobagyi GN. Emerging targeted therapies for breast cancer. J Clin Oncol.2010;28(20):3366–3379.

18. Senkus E, Kyriakides S, Penault-Llorca F, et al; ESMO Guidelines Working Group. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24 Suppl 6:vi7–vi23.

19. NCCN. NCCN guidelines. Breast cancer, version 3; 2017. Available from: Accessed March 2, 2017.

20. Haffty BG, Yang Q, Reiss M, et al. Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer. J Clin Oncol. 2006;24(36):5652–5657.

21. Trendell-Smith NJ, Peston D, Shousha S. Adenoid cystic carcinoma of the breast: a tumour commonly devoid of oestrogen receptors and related proteins. Histopathology. 1999;35(3):241–248.

22. Lehmann BD, Bauer JA, Chen X, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011;121(7):2750–2767.

23. Pusztai L. Gene expression profiling of breast cancer. Breast Cancer Res. 2009;11 Suppl(3):S11.

24. Bertucci F, Finetti P, Cervera N, et al. How basal are triple-negative breast cancers? Int J Cancer. 2008;123(1):236–240.

25. Badve S, Dabbs DJ, Schnitt SJ, et al. Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists. Mod Pathol. 2011;24(2):157–167.

26. Choo JR, Nielsen TO. Biomarkers for Basal-like Breast Cancer. Cancers (Basel). 2010;2(2):1040–1065.

27. Rakha EA, El-Sayed ME, Green AR, Lee AH, Robertson JF, Ellis IO. Prognostic markers in triple-negative breast cancer. Cancer. 2007;109(1):25–32.

28. Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17(6):1471–1474.

29. Elston CW, Ellis IO. 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. 1991;19(5):403–410.

30. Rosen PP, Saigo PE, Braun DW Jr, Weathers E, DePalo A. Predictors of recurrence in stage I (T1N0M0) breast carcinoma. Ann Surg. 1981;193(1):15–25.

31. Bradburn MJ, Clark TG, Love SB, Altman DG. Survival analysis Part III: multivariate data analysis — choosing a model and assessing its adequacy and fit. Br J Cancer. 2003;89(4):605–611.

32. Kashiwagi S, Yashiro M, Takashima T, et al. Significance of E-cadherin expression in triple-negative breast cancer. Br J Cancer. 2010;103(2):249–255.

33. Won JR, Gao D, Chow C, et al. A survey of immunohistochemical biomarkers for basal-like breast cancer against a gene expression profile gold standard. Mod Pathol. 2013;26(11):1438–1450.

34. Nielsen TO, Hsu FD, Jensen K, et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res. 2004;10(16):5367–5374.

35. Adams S, Gray RJ, Demaria S, et al. Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199. J Clin Oncol. 2014;32(27):2959–2966.

36. Wang C, Pan B, Zhu H, et al. Prognostic value of androgen receptor in triple negative breast cancer: A meta-analysis. Oncotarget. 2016;7(29):46482–46491.

37. Urruticoechea A, Smith IE, Dowsett M. Proliferation marker Ki-67 in early breast cancer. J Clin Oncol.2005;23(28):7212–7220.

38. de Azambuja E, Cardoso F, de Castro G Jr, et al. Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12,155 patients. Br J Cancer. 2007;96(10):1504–1513.

39. Wang W, Wu J, Zhang P, et al. Prognostic and predictive value of Ki-67 in triple-negative breast cancer. Oncotarget. 2016;7(21):31079–31087.

40. Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2001;2(2):127–137.

41. Siziopikou KP, Ariga R, Proussaloglou KE, Gattuso P, Cobleigh M. The challenging estrogen receptor-negative/ progesterone receptor-negative/HER-2-negative patient: a promising candidate for epidermal growth factor receptor-targeted therapy? Breast J. 2006;12(4):360–362.

42. Viale G, Rotmensz N, Maisonneuve P, et al. Invasive ductal carcinoma of the breast with the “triple-negative” phenotype: prognostic implications of EGFR immunoreactivity. Breast Cancer Res Treat. 2009;116(2):317–328.

43. Andrews JL, Kim AC, Hens JR. The role and function of cadherins in the mammary gland. Breast Cancer Res. 2012;14(1):203.

44. Gumbiner BM. Regulation of cadherin-mediated adhesion in morphogenesis. Nat Rev Mol Cell Biol. 2005;6(8):622–634.

45. Baranwal S, Alahari SK. Molecular mechanisms controlling E-cadherin expression in breast cancer. Biochem Biophys Res Commun. 2009;384(1):6–11.

46. Gould Rothberg BE, Bracken MB. E-cadherin immunohistochemical expression as a prognostic factor in infiltrating ductal carcinoma of the breast: a systematic review and meta-analysis. Breast Cancer Res Treat. 2006;100(2):139–148.

47. Thiery JP. Epithelial–mesenchymal transitions in tumour progression. Nat Rev Cancer. 2002;2(6):442–454.

48. Prat A, Parker JS, Karginova O, et al. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res. 2010;12(5):R68.

49. Mahler-Araujo B, Savage K, Parry S, Reis-Filho JS. Reduction of E-cadherin expression is associated with non-lobular breast carcinomas of basal-like and triple negative phenotype. J Clin Pathol. 2008;61(5):615–620.

50. Cheang MC, Voduc D, Bajdik C, et al. Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin Cancer Res. 2008;14(5):1368–1376.

51. Pintens S, Neven P, Drijkoningen M, et al. Triple negative breast cancer: a study from the point of view of basal CK5/6 and HER-1. J Clin Pathol. 2009;62(7):624–628.

52. Rao C, Shetty J, Prasad KH. Immunohistochemical profile and morphology in triple – negative breast cancers. J Clin Diagn Res. 2013;7(7):1361–1365.

53. Sutton LM, Han JS, Molberg KH, et al. Intratumoral expression level of epidermal growth factor receptor and cytokeratin 5/6 is significantly associated with nodal and distant metastases in patients with basal-like triple-negative breast carcinoma. Am J Clin Pathol. 2010;134(5):782–787.

54. Kutomi G, Ohmura T, Suzuki Y, Hirata K. History and future of surgical treatment. Nihon Rinsho. 2012;70 Suppl(7):13–17. Japanese.

55. Inanc M, Ozkan M, Karaca H, et al. Cytokeratin 5/6, c-Met expressions, and PTEN loss prognostic indicators in triple-negative breast cancer. Med Oncol. 2014;31(1):801.

56. Adamo B, Ricciardi GRR, Ieni A, et al. The prognostic significance of combined androgen receptor, E-Cadherin, Ki67 and CK5/6 expression in patients with triple negative breast cancer. Oncotarget. 2017;8(44):76974–76986.

57. Lacroix M, Toillon RA, Leclercq G. p53 and breast cancer, an update. Endocr Relat Cancer. 2006;13(2):293–325.

58. Tsuda H, Hirohashi S. Association among p53 gene mutation, nuclear accumulation of the p53 protein and aggressive phenotypes in breast cancer. Int J Cancer. 1994;57(4):498–503.

59. Soussi T, Béroud C. Assessing TP53 status in human tumours to evaluate clinical outcome. Nat Rev Cancer. 2001;1(3):233–240.

60. Olivier M, Langerød A, Carrieri P, et al. The clinical value of somatic TP53 gene mutations in 1,794 patients with breast cancer. Clin Cancer Res. 2006;12(4):1157–1167.

61. Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490(7418):61–70.

62. Gajdos C, Tartter PI, Bleiweiss IJ. Lymphatic invasion, tumor size, and age are independent predictors of axillary lymph node metastases in women with T1 breast cancers. Ann Surg. 1999;230(5):692–696.

63. Ding L, Ellis MJ, Li S, et al. Genome remodelling in a basal-like breast cancer metastasis and xenograft. Nature. 2010;464(7291):999–1005.

64. Pan Y, Yuan Y, Liu G, Wei Y. P53 and Ki-67 as prognostic markers in triple-negative breast cancer patients. PLoS One. 2017;12(2):e0172324.

65. Biganzoli E, Coradini D, Ambrogi F, et al. p53 status identifies two subgroups of triple-negative breast cancers with distinct biological features. Jpn J Clin Oncol. 2011;41(2):172–179.

66. Coates AS, Millar EK, O’Toole SA, et al. Prognostic interaction between expression of p53 and estrogen receptor in patients with node-negative breast cancer: results from IBCSG Trials VIII and IX. Breast Cancer Res. 2012;14(6):R143.

67. Chae BJ, Bae JS, Lee A, et al. p53 as a specific prognostic factor in triple-negative breast cancer. Jpn J Clin Oncol. 2009;39(4):217–224.

68. Basu A, Haldar S. The relationship between BcI2, Bax and p53: consequences for cell cycle progression and cell death. Mol Hum Reprod. 1998;4(12):1099–1109.

69. Tsujimoto Y, Finger LR, Yunis J, Nowell PC, Croce CM. Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science. 1984;226(4678):1097–1099.

70. Leung LK, Wang TT. Paradoxical regulation of Bcl-2 family proteins by 17beta-oestradiol in human breast cancer cells MCF-7. Br J Cancer. 1999;81(3):387–392.

71. Dawson SJ, Makretsov N, Blows FM, et al. BCL2 in breast cancer: a favourable prognostic marker across molecular subtypes and independent of adjuvant therapy received. Br J Cancer. 2010;103(5):668–675.

72. Abdel-Fatah TM, Perry C, Dickinson P, et al. Bcl2 is an independent prognostic marker of triple negative breast cancer (TNBC) and predicts response to anthracycline combination (ATC) chemotherapy (CT) in adjuvant and neoadjuvant settings. Ann Oncol. 2013;24(11):2801–2807.

73. Tawfik K, Kimler BF, Davis MK, Fan F, Tawfik O. Prognostic significance of Bcl-2 in invasive mammary carcinomas: a comparative clinicopathologic study between “triple-negative” and non-”triple-negative” tumors. Hum Pathol. 2012;43(1):23–30.

74. Nielsen KV, Ejlertsen B, Møller S, et al. The value of TOP2A gene copy number variation as a biomarker in breast cancer: Update of DBCG trial 89D. Acta Oncol. 2008;47(4):725–734.

75. Arriola E, Rodriguez-Pinilla SM, Lambros MB, et al. Topoisomerase II alpha amplification may predict benefit from adjuvant anthracyclines in HER2 positive early breast cancer. Breast Cancer Res Treat. 2007;106(2):181–189.

76. Mrklić I, Pogorelić Z, Ćapkun V, Tomić S. Expression of topoisomerase II-α in triple negative breast cancer. Appl Immunohistochem Mol Morphol. 2014;22(3):182–187.

77. Calhoun BC, Lanigan C, Rubin B, Mrazeck KC, Rosa C, Barnes M. TOP2A-based prognostication in triple negative breast cancer and correlation with basal phenotype. J Clin Oncol. 2015;33(Suppl 15):1098.

78. Rao AM, Hatcher JF, Dempsey RJ. Lipid alterations in transient forebrain ischemia: possible new mechanisms of CDP-choline neuroprotection. J Neurochem. 2000;75(6):2528–2535.

79. Dubois RN, Abramson SB, Crofford L, et al. Cyclooxygenase in biology and disease. FASEB J. 1998;12(12):1063–1073.

80. Costa C, Soares R, Reis-Filho JS, Leitão D, Amendoeira I, Schmitt FC. Cyclo-oxygenase 2 expression is associated with angiogenesis and lymph node metastasis in human breast cancer. J Clin Pathol. 2002;55(6):429–434.

81. Subbaramaiah K, Norton L, Gerald W, Dannenberg AJ. Cyclooxygenase-2 is overexpressed in HER-2/neu-positive breast cancer: evidence for involvement of AP-1 and PEA3. J Biol Chem. 2002;277(21):18649–18657.

82. Witton CJ, Hawe SJ, Cooke TG, Bartlett JM. Cyclooxygenase 2 (COX2) expression is associated with poor outcome in ER-negative, but not ER-positive, breast cancer. Histopathology. 2004;45(1):47–54.

83. Klapper LN, Glathe S, Vaisman N, et al. The ErbB-2/HER2 oncoprotein of human carcinomas may function solely as a shared coreceptor for multiple stroma-derived growth factors. Proc Natl Acad Sci U S A. 1999;96(9):4995–5000.

84. Karamouzis MV, Dalagiorgou G, Georgopoulou U, Nonni A, Kontos M, Papavassiliou AG. HER-3 targeting alters the dimerization pattern of ErbB protein family members in breast carcinomas. Oncotarget. 2016;7(5):5576–5597.

85. Witton CJ, Reeves JR, Going JJ, Cooke TG, Bartlett JM. Expression of the HER1-4 family of receptor tyrosine kinases in breast cancer. J Pathol. 2003;200(3):290–297.

86. Torrisi R, Rotmensz N, Bagnardi V, et al. HER2 status in early breast cancer: relevance of cell staining patterns, gene amplification and polysomy 17. Eur J Cancer. 2007;43(16):2339–2344.

87. Chia S, Norris B, Speers C, et al. Human epidermal growth factor receptor 2 overexpression as a prognostic factor in a large tissue microarray series of node-negative breast cancers. J Clin Oncol. 2008;26(35):5697–5704.

88. Schmidt G, Meyberg-Solomayer G, Gerlinger C, et al. Identification of prognostic different subgroups in triple negative breast cancer by Her2-neu protein expression. Arch Gynecol Obstet. 2014;290(6):1221–1229.

89. Ilie SM, Desauw C, Hebbar M. HER2 based expression subpopulations in TNBC: pathological aspects and clinical significance. Ann Oncol. 2016;27suppl(6):vi15–vi42.

90. Thike AA, Iqbal J, Cheok PY, et al. Triple negative breast cancer: outcome correlation with immunohistochemical detection of basal markers. Am J Surg Pathol. 2010;34(7):956–964.

91. Rhee J, Han SW, Oh DY, et al. The clinicopathologic characteristics and prognostic significance of triple-negativity in node-negative breast cancer. BMC Cancer. 2008;8:307.

92. Kashiwagi S, Yashiro M, Takashima T, et al. Advantages of adjuvant chemotherapy for patients with triple-negative breast cancer at Stage II: usefulness of prognostic markers E-cadherin and Ki67. Breast Cancer Res. 2011;13(6):R122.

93. Miyashita M, Ishida T, Ishida K, et al. Histopathological subclassification of triple negative breast cancer using prognostic scoring system: five variables as candidates. Virchows Arch. 2011;458(1):65–72.

Source: Breast Cancer: Targets and Therapy.
Originally published November 23, 2018.