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Triple-Negative Breast Cancer: Analysis of Patients Diagnosed and/or Treated at the Masaryk Memorial Cancer Institute between 2004 and 2009


Authors: M. Svoboda 1,2;  J. Navrátil 1;  P. Fabian 3;  M. Palacova 1;  J. Gombošová 4;  L. Slámová 1;  D. Princ 4;  B. Syptáková 4;  A. Kudláček 4;  O. Bílek 1;  P. Pospíšil 4;  T. Kazda 4;  P. Grell 1;  A. Poprach 1;  I. Selingerová 5;  R. Nenutil 3;  J. Juráček 1;  R. Héžová 1;  O. Slabý 1;  R. Vyzula 1
Authors place of work: Klinika komplexní onkologické péče, MOÚ Brno 1;  Oddělení epidemiologie a genetiky nádorů, MOÚ Brno 2;  Oddělení onkologické a experimentální patologie, MOÚ Brno 3;  Klinika radiační onkologie, MOÚ Brno 4;  Ústav matematiky a statistiky, PřF MU Brno 5
Published in the journal: Klin Onkol 2012; 25(3): 188-198
Category: Original Articles

Summary

Background:
Triple-negative breast cancer (TNBC) represents a heterogeneous group of breast cancers that do not express ER-α, PgR and Her-2 receptors. Generally, these tumors are aggressive and more common in younger women, in which an association of TNBC with mutations in the BRCA1 gene was documented. The aim of our study was to create a representative group of patients with TNBC, which could be analyzed and the data gathered to build basic epidemiological, molecular and clinical characteristics of Czech patients with TNBC.

Patients and Methods:
We performed basic clinical-pathologic correlations in a group of 335 patients diagnosed and/or treated for TNBC at the Masaryk Memorial Cancer Institute between 2004 and 2009. We also performed immunohistochemical examination of expression of cytokeratin 5/6, cytokeratin 14 and EGFR to identify the ‘basal-like’ subset of TNBC.

Results:
The median age of patients with TNBC was 56 years, range 25–88 years. A total of 9.25% of TNBC cases were diagnosed in patients under the age of 34, and another 15.22% of cases were in the age group of 35 to 44 years. ‘Basal-like’ carcinomas accounted for 75% of TNBC. We confirmed the aggressive nature of this disease: in the follow-up period we observed a relapse in 25% of patients: 55% of deaths due to disease progression occured within 2 years after diagnosis of the disease. Treatment strategies include chemotherapy, in most cases (88.4%). Chemotherapy was mostly based on regimens with anthracyclines or in combination with taxanes. The most important negative prognostic factors in relation to OS (disease specific OS) were: higher clinical stage (p < 0.0001), pN – positive status (p < 0.0001), high proliferative activity (as measured by Ki-67, cut-off 50%, HR = 0.4740, p = 0.0411) and positive expression of CK5/6 (HR = 0.4274, p = 0.0338). In relation to DFS, the negative prognostic significance was found for these factors: higher clinical stage (p < 0.0001), pN positive status (p < 0.0001), high proliferative activity (Ki-67, cut-off 50%, HR = 0.04993, p = 0.0240). DFS was longer in patients with a higher number of applied cycles of anthracycline-based chemotherapy (> 4 cycles, HR = 1.7273, p = 0.0467).

Conclusion:
TNBC is an aggressive form of breast cancer, which may occur in patients of all ages, but more frequently in younger patients. Only early detection of disease and intensive treatment gives a high chance of cure. Unfortunately, no reliable predictive factors have been identified so far. Better therapeutic results can be expected from targeted therapy.

Key words:
triple-negative breast cancer – cytokeratin 5/6 – Ki-67 protein – chemotherapy – breast cancer

This study was supported by the following research programmes:
NO. NS/10357-3 of the Internal Grant Agency, Ministry of Health of the Czech Republic; No. CZ.1.07/2.4.00/17.0100. – A-MATH-NET, Ministry of Education, Youth and Sports of the Czech Republic.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.

Submitted:
26. 2. 2012

Accepted:
21. 5. 2012


Zdroje

1. Dušek L, Mužík J, Kubásek M et al. Epidemiologie zhoubných nádorů v České republice republice [online]. Masarykova univerzita 2005 [cit. 2012-5-31]. Dostupný z: http://www.svod.cz.

2. Ellis IO, Schnitt SJ, Sastre-Garau X et al. Invasive breast carcinoma. In: Tavassoli FA, Devilee P (eds). Pathology and Genetics of Tumours of the Breast and Female Genital Organs. 3rd ed. Lyon: WHO and IARC Press 2003: 13–60.

3. Svoboda M, Grell P, Fabian P et al. Molekulární taxonomie a prediktivní systémy karcinomu prsu definované na základě profilů genové exprese. Klin Onkol 2006; 19 (Supp 2): 373–381.

4. Jatoi I, Chen BE, Anderson WF et al. Breast cancer mortality trends in the United States according to estrogen receptor status and age at diagnosis. J Clin Oncol; 25(13): 1683–1690.

5. Piccart-Gebhart MJ, Procter M, Leyland-Jones B et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005; 353(16): 1659–1672.

6. Gianni L, Eirmann W, Semiglazov V et al. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet 2010; 375(9712): 377–384.

7. Perou CM, Sørlie T, Eisen MN et al. Molecular portraits of human breast tumours. Nature 2000; 406(6796): 747–752.

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

9. Valentin MD, da Silva SD, Privat M et al. Molecular insights on basal-like breast cancer. Breast Cancer Res Treat 2012. In press.

10. Goldhirsch A, Wood WC, Coates AS et al. Strategies for subtypes-dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol 2011; 22(8): 1736–1747.

11. Minami CA, Chung DU, Chang HR. Management op­tions in triple-negative breast cancer. Breast Cancer (Auckl) 2011; 5: 175–199.

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

13. Rakha EA, Reis-Filho JS, Ellis IO. Basal-like breast cancer: a critical review. J Clin Oncol 2008; 26(15): 2568–2581.

14. Lakhani SR, Reis-Filho JS, Fulford L et al. Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype. Clin Cancer Res 2005; 11(14): 5175–5180.

15. Kandel MJ, Stadler Z, Masciari S et al. Prevalence of BRCA1 mutatitons in triple-negative breast cancer (BC). J Clin Oncol 2006; 24 (Suppl 18): Abstract 508.

16. Bauer KR, Brown M, Cress RD et al. Descriptive analysis of estrogen receptor (ER)-negative, progesterone 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 2007; 109(9): 1721–1728.

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

18. Svoboda M, Fabian P, Ondrová B et al. Brain metastases in breast cancer: a retrospective cohort study of 187 patients and prognostic markers determination. Breast Cancer Res Treat 2007; 106 (Supp 1): S253.

19. Silver DP, Richardson A, Eklund AC et al. Efficacy of neoadjuvant Cisplatin in triple-negative breast cancer. J Clin Oncol 2010; 28(7): 1145–1153.

20. Chang HR, Glaspy J, Allison MA et al. Differential response of triple-negative breast cancer to a docetaxel and carboplatin-based neoadjuvant treatment. Cancer 2010; 116(18): 4227–4237.

21. Torrisi R, Balduzzi A, Ghisini R et al. Tailored preoperative treatment of locally advanced triple negative (hormone receptor negative and HER2 negative) breast cancer with epirubicin, cisplatin, and infusional fluorouracil followed by weekly paclitaxel. Cancer Chemother Pharmacol 2007; 62(4): 667–672.

22. Frasci G, Comella P, Rinaldo M et al. Preoperative weekly cisplatin-epirubicin-paclitaxel with G-CSF support in triple-negative large operable breast cancer. Ann Oncol 2009; 20(7): 1185–1192.

23. Dusek L, Muzik J, Gelnarova E et al. Cancer incidence and mortality in the Czech Republic. Klin Onkol 2010; 23(5): 311–324.

24. Yan M, Rayoo M, Takano EA et al. Nuclear and cytoplasmic expressions of ERβ1 and ERβ2 are predictive of response to therapy and alters prognosis in familial breast cancers. Breast Cancer Res Treat 2011; 126(2): 395–405.

25. Novelli F, Milella M, Melucci E et al. A divergent role for estrogen receptor-beta in node-positive and node-negative breast cancer classified according to molecular subtypes: an observational prospective study. Breast Cancer Res 2008; 10(5): R74.

26. Bouchalova K, Svoboda M, Kharaishvili G et al. BCL2 protein in prediction of relapse in triple-negative breast cancer (TNBC) treated with adjuvant anthracycline-based chemotherapy. J Clin Oncol 2012; 30 (Suppl): Abstract 1087.

27. 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.

28. Fulford G, Reis-Filho JS, Ryder K et al. Basal-like grade III invasive ductal carcinoma of the breast: patterns of metastasis and long-term survival. Breast Cancer Res 2007; 9(1): R4.

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

Štítky
Paediatric clinical oncology Surgery Clinical oncology

Článok vyšiel v časopise

Clinical Oncology

Číslo 3

2012 Číslo 3
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