DOI QR코드

DOI QR Code

Expression of Nuclear Factor Kappa B (NF-κB) as a Predictor of Poor Pathologic Response to Chemotherapy in Patients with Locally Advanced Breast Cancer

  • Prajoko, Yan Wisnu (Department of Surgery, Faculty of Medicine, Diponegoro University) ;
  • Aryandono, Teguh (Department of Surgery, Faculty of Medicine, Gadjah Mada University)
  • Published : 2014.01.30

Abstract

Background: NF-${\kappa}B$ inhibits apoptosis through induction of antiapoptotic proteins and suppression of proapoptotic genes. Various chemotherapy agents induce NF-${\kappa}B$ translocation and target gene activation. We conducted the present study to assess the predictive value of NF-${\kappa}B$ regarding pathologic responses after receiving neoadjuvant chemotherapy. Materials and Methods: We enrolled 131 patients with locally advanced invasive ductal breast carcinoma. Immunohistochemistry (IHC) was used to detect NF-${\kappa}B$ expression. Evaluation of pathologic response was elaborated with the Ribero classification. Results: Expression of NF-${\kappa}B$ was significantly associated with poor pathological response (p=0.02). From the multivariate analysis, it was found that the positive expression of NF-${\kappa}B$ yielded RR=1.74 (95%CI 0.77 to 3.94). Conclusions: NF-${\kappa}B$ can be used as a predictor of poor pathological response after neoadjuvant chemotherapy.

Keywords

References

  1. Barre B, Coqueret O, Perkins ND (2010). Regulation of activity and function of the p52 NF-$\kappa{B}$ subunit following DNA damage. Cell Cycle, 9, 4795-804. https://doi.org/10.4161/cc.9.24.14245
  2. Basseres DS, Baldwin AS (2006). Nuclear factor-$\kappa{B}$ and inhibitor of $\kappa{B}$ kinase pathways in oncogenic initiation and progression. Oncogene, 25, 5817-30.
  3. Bourgarel-Rey V, Vallee S, Rimet O, et al (2001). Involvement of nuclear factor b in c-myc induction by tubulin polymerization inhibitors. Mol Pharmacol, 59, 1165-70.
  4. Chang JC, Hilsenbeck SG (2004). Prognostic and predictive markers. In: Harris JR et al, (eds) Diseases of The Breast. 3rd ed. Philadelphia: Lippincott Williams & Wilkins, pp.675-96.
  5. Chen ZS, Tiwari AK (2011). Multidrug resistance proteins (MRPs/ABCCs) in cancer chemotherapy and genetic diseases. FEBS J, 278, 3226-45. https://doi.org/10.1111/j.1742-4658.2011.08235.x
  6. Chuthapisith S, Eremin JM, El-Sheemy M, Eremin O (2006). Neoadjuvant chemotherapy in women with large and locally advanced breast cancer: chemoresistance and prediction of response to drug therapy. Surgeon, 4, 211-9. https://doi.org/10.1016/S1479-666X(06)80062-4
  7. Fan Y, Dutta J, Gupta N, Fan G, Gelinas C (2008). Regulation of programmed cell death by NF-kappaB and its role in tumorigenesis and therapy. Adv Exp Med Biol, 615, 223-50. https://doi.org/10.1007/978-1-4020-6554-5_11
  8. Ghavami S, Hashemi M, Ande SR, et al (2009). Apoptosis and cancer: mutations within caspase genes. J Med Genet, 46, 497-510. https://doi.org/10.1136/jmg.2009.066944
  9. Godwin P, Baird AM, Heavey S, Barr MP, Gately K (2013), Targeting nuclear factor-kappa B to overcome resistance to chemotherapy. Front Oncol, 3, 1-10.
  10. Gonzalez-Angulo AM, McGuire SE, Buchholz TA, et al (2005). Factors predictive of distant metastases in patients with breast cancer who have a pathologic complete response after neoadjuvant chemotherapy. J Clin Oncol, 23, 7098-104. https://doi.org/10.1200/JCO.2005.11.124
  11. IARC (2008). GLOBOCAN 2008, Section of Cancer Information.
  12. Jones RL, Rojo F, A'Hern R, et al (2011). Nuclear NF-kappa B/p65 expression and response to neoadjuvant chemotherapy in breast cancer. J Clin Path, 64, 130-5. https://doi.org/10.1136/jcp.2010.082966
  13. O'Gorman DM, Cotter TG (2011). Molecular signals in antiapoptotic survival pathways. Leukemia, 15, 21-34.
  14. Schott AF, Hayes DF (2012). Defining the benefits of neoadjuvant chemotherapy for breast cancer. J Clin Oncol, 30, 1747-9. https://doi.org/10.1200/JCO.2011.41.3161
  15. Smith IC, Heys SD, Hutcheon AW, et al (2002). Neoadjuvant chemotherapy in breast cancer: significantly enhanced response with docetaxel. J Clin Oncol, 20, 1456-66. https://doi.org/10.1200/JCO.20.6.1456
  16. Voborilova J, Nemcova-Furstova V, Neubauerova J, et al (2011). Cell death induced by novel fluorinated taxanes in drug-sensitive and drug-resistant cancer cells. Invest New Drugs, 29, 411-23. https://doi.org/10.1007/s10637-009-9368-8
  17. Von Minckwitz G, Untch M, Blohmer JU, et al (2012). Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol, 30, 1-10. https://doi.org/10.1200/JCO.2011.38.2747

Cited by

  1. Molecular mechanism underlying the anticancer effect of simvastatin on MDA-MB-231 human breast cancer cells vol.12, pp.1, 2012, https://doi.org/10.3892/mmr.2015.3411
  2. ATAD2 is Highly Expressed in Ovarian Carcinomas and Indicates Poor Prognosis vol.15, pp.6, 2014, https://doi.org/10.7314/APJCP.2014.15.6.2777
  3. Long-Term Survival of Women with Locally Advanced Breast Cancer with ≥10 Involved Lymph Nodes at Diagnosis vol.15, pp.8, 2014, https://doi.org/10.7314/APJCP.2014.15.8.3435