EVALUATION OF CASPASE 3 AS AN INDICATOR FOR BREAST CANCER CHEMOTHERAPY RESPONSE
Objectives: This study aimed to assess the difference of postchemotherapy caspase 3 level between triple negative breast cancer (TNBC) subjects with and without clinical response.
Methods: A total of 48 subjects with intraductal and 12 subjects with intralobular TNBC who were undergoing surgery at Adam Malik General Hospital were analyzed the response of neoadjuvant chemotherapy. Postsurgical breast tumor tissue was treated in pathology laboratory for caspase 3 analysis. The data were processed in SPSS 22 with significance limitation of 0.05.
Results: Median levels of caspase 3 postchemotherapy were higher both in intraductal and intralobular TNBC subtype (6 vs. 4.5 and 5 vs. 3, respectively) responsive group, while no changes detected in the group without clinical response. In statistical analysis, there was a significant difference of caspase 3 level postchemotherapy only in group with clinical response (p=0.005 in intraductal carcinoma and p=0.0031 in intralobular carcinoma).
Conclusion: Postchemotherapy caspase 3 level increased significantly in TNBC, either intraductal or intralobular subtype, subjects with clinical response, but not in subjects without clinical response.
2. PERABOI Cabang Medan. Laporan Kegiatan Dan Rencana Kerja Dua Tahunan Divisi Bedah Onkologi FK-USU/RSUP.H.ADAM MALIK; 2014.
3. Wu J, Li S, Jia W, Su F. Response and prognosis of taxanes and anthracyclines neoadjuvant chemotherapy in patients with triple-negative breast cancer. J Cancer Res Clin Oncol 2001;137:1505-10.
4. Kirthi C, Adzal A, Reddy M, Ali SA, Yerramilli A, Sharma S. A study on the adverse effects of anticancer drugs in an oncology center of a tertiary care hospital. Int J Pharm Pharm Sci 2014;6:580-3.
5. Fisher B, Brown A, Mamounas E, Wieand S, Robidoux A, Margolese R, et al. Effect of preoperative chemotherapy on local-regional disease in wome with operable breast cancer: Findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol 1997;15:2483-93.
6. Cleator S, Parton M, Dowsett M. The biology of neoadjuvant chemotherapy for breast cancer. Endocrine Related Cancer 2002;9:183-95.
7. Indran R, Tufo G, Pervaiz S, Brenner C. Recent advances in apoptosis, mitochondria and drug resistance in cancer cells. Biochim Biophys Acta 2011;1807:735-45.
8. Rakha E, Ellis I, Reis-Filho J. Are triple-negative and basal-like breast cancer synonymous? Clin Cancer Res 2008;14:618-9.
9. Bai-lin Z, Tong S, Zhang B, Zheng S, Ning LU. Polymorphisms of GSTP1 is associated with differences of chemotherapy response and toxicity in breast cancer. ??? 2011;124:199-204.
10. Vakkala M, PÃ¤Ã¤kkÃ¶ P, Soni Y. Expression of caspases 3, 6 and 8 is increased in parallel with apoptosis and histological aggressiveness of the breast lesion. Br J Cancer 1999;81:592-9.
11. Dawood S, Broglio K, Esteva FJ. Survival among women with triple receptornegative breast cancer and brain metastases. Ann Oncol 2009;20:621-7.
12. Koya S, Li Y, McDaniel S. Safety and effectiveness of dose dense neoadjuvant chemotherapy in patients with stage II/III breast cancer. J Clin Oncol 2009;27:e11566.
13. Smith JW 2nd, McIntyre KJ, Acevedo PV. Results of a phase II open-label, nonrandomized trial of oral satraplatin in patients with metastatic breast cancer. Breast Cancer Res Treat 2009;118:361-7.
14. West DC, McGrowder DA. Triple negative breast cancer: Therapeutic and prognostic implications. Asian Pac J Cancer Prev 2011;12:2129-33.
15. Lakhani S, Ellis I, Schnitt S, Tan P, van de Vijver M. WHO Classification of Tumours of the Breast. 4th ed. Lyon, France: International Agency for Research on Cancer; 2012.
16. Shampoo MA, Kyle RA. Pioneers of mammography-warren and egan. Mayo Clin Proc 1997;72:32-5.
17. Rosner D, Bedwani RN, Vana J. Noninvasive breast carcinoma. Results of a national survey by the American College of Surgeons. Ann Surg 1980;192:139-47.
18. Sanders ME, Schuyler PA, Dupont WD, Page DL. The natural history of low-grade ductal carcinoma in situ of the breast in women treated by biopsy only revealed over 30 years of long-term follow-up. Cancer 2005;103:2481-4.
19. Hanagiri T, Nozoe T, Mizukami M, Ichiki Y, Sugaya M, Yasuda M, et al. Clinicopathological characteristics of invasive lobular carcinoma of the breast. Asian J Surg 2009;32:76-80.
20. Iorfida M, Maiorano E, Orvieto E, Maisonneuve P, Bottiglieri L, Rotmensz N, et al. Invasive lobular breast cancer: Subtypes and outcome. Breast Cancer Res Treat 2012;133:713-23.
21. Butler RS, Venta LA, Wiley EL, Ellis RL. Sonographic evaluation of infiltrating lobular carcinoma. AJR Am J Roentgenol 1999;172:325-30.
22. McCart RA, Kutasovic J, Lakhani S, Simpson P. Invasive lobular carcinoma of the breast: Morphology, biomarkers and â€˜omics. Breast Cancer Res 2015;17:12-5.
23. Gianni L, Eiermann W, Semiglazov V, Manikhas A, Lluch A, Tjulandin S, 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;375:377-84.
24. Tewari M, Pradhan S, Singh U, Singh TB, Shukla HS. Assessment of predictive markers of response to neoadjuvant chemotherapy in breast cancer. Asian J Surg 2010;33:157-67.
25. Viale G. Characterization and clinical impact of residual disease after neoadjuvant chemotherapy. Breast 2013;22:88-91.
26. BlÃ¡zquez S, Sirvent J, Olona M, Aguilar C, Pelegri A, Garcia JF, et al. Caspase-3 and Caspase-6 in ductal breast carcinoma: A descriptive study. Histol Histopathol 2006;21:1321-29.
27. Luo M, Lu Z, He S, Yuan K, Zhang Q, Sha M, et al. Nuclear entry of active caspase-3 is facilitated by its p3-recognition-based specific cleavage activity. Cell Res 2010;1:211-22.
28. Salako O, Poku R, Nkembo A, Amissah F, Ntantie E, Lamango N. Treatment of triple negative breast cancer-derived cells with polyisoprenylated cysteinyl amide inhibitors activates caspase 3/7 and disrupts f-actin organization leading to apoptosis and diminished cell motility. FASEB 2016;30:1-3.
29. Oâ€™Donovan N, Crown J, Stunnel H, Hill AD, McDermott E, Oâ€™Higgins N, et al. Caspase 3 in breast cancer. Clin Cancer Res 2003;9:738-42.
30. Branham KS, Krishna VM, Gopal SV, Raju AJ. Evaluation of caspase-3 as a possible indicator of apoptotic activity to assess the chemoresistance/sensitivity. J Pharm Res 2012;5:229-231.
31. dos Santos N, Silva RF, Pinto MM, Silva EB, Tasat DR, Amaral A. Active caspase-3 expression levels as bioindicator of individual radiosensitivity. Anais Acad Brasil Ciencias 2017;89:649-59.
32. Yang XH, Sladek TL, Liu X. Reconstitution of Caspase-3 sensitizes MCF-7 breast cancer cells to doxorubicin- and etoposide-induced apoptosis. Cancer Res 2001;61:348-54.
33. Amelio MD, Cavalluci V, Cecconi F. Neuronal caspase-3 signaling: Not only cell death. Cell Death Differ 2010;17:1104-14.
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.