scholarly journals Apoptotic Index Fails to Predict Chemoresponse in Breast Cancer

2019 ◽  
Vol 2 (2) ◽  
pp. 55-60
Author(s):  
Kamal Basri Siregar

The responsiveness of neoadjuvant chemotherapy in Triple Negative Breast Cancer (TNBC) needs determination to prevent overtreatment with chemoresistance regimen. A total of 60 consented patients from Haji Adam Malik and Bunda Thamrin Hospital were included in this cohort prospectie study. Patients with heart, kidney, liver disease, history of surgery, chemotherapy, or hormonal therapy were excluded. Apoptotic indexes were taken from all subjects before and after neoadjuvant chemotherapy. After 3 cycles of neoadjuvant chemotherapy, 31 subjects (51.7%) did not show clinical response while 29 subjects (48.3%) had clinical response. There was no significant difference of apoptotic index before and after neoadjuvant chemotherapy (5.47+1.38 vs 5.52+1.08 pg/mL). There was also no significant relationship between apoptosis index and clinical response (p=0.993). This study showed that apoptotic index fails to be neoadjuvant chemotherapy response predictor in triple negative breast cancer. Further research with larger samples is needed to confirm this result

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Neslihan Cabioglu ◽  
Semen Onder ◽  
Gizem Oner ◽  
Hüseyin Karatay ◽  
Mustafa Tukenmez ◽  
...  

Abstract Background The expression of immune checkpoint receptors (ICRs) on tumor-infiltrating lymphocytes (TILs) is associated with better response to immunotherapies via immune checkpoint inhibitors. Therefore, we investigated various ICR expressions on TILs in patients with locally advanced triple-negative breast cancer (TNBC) after neoadjuvant chemotherapy (NAC). Methods Expressions of ICRs were examined immunohistochemically in surgical specimens (n = 61) using monoclonal antibodies for PDL-1, PD-1, TIM-3, LAG-3, and CTLA-4. Positivity was defined as staining > 1% on TILs. Results The median age was 49 (24–76) years. The majority of patients were clinically T3–4 (n = 31, 50.8%) and clinically N1–3 (n = 58, 95.1%) before NAC. Of those, 82% were found to have CTLA-4 positivity, whereas PD1, PDL-1, LAG3, and TIM-3 expressions on TILs were 62.3, 50.9, 26.2, and 68.9%. A high expression of CTLA-4 was found to be associated with a better chemotherapy response (OR = 7.94, 95% CI: 0.9–70.12, p = 0.06), whereas TIM-3 positivity was contrarily associated with a worse chemotherapy response (OR = 0.253, 95% CI: 0.066–0.974, p = 0.047) as measured by the MDACC Residual Cancer Burden Index. At a 47-month follow-up, ypN0 (DFS; HR = 0.31, 95% CI: 0.12–0.83, p = 0.02 and DSS; HR = 0.21, 95% CI: 0.07–0.62, p = 0.005) and CTLA-4 high expression on TILs (DFS; HR = 0.38, 95% CI: 0.17–0.85, p = 0.019 and DSS; HR = 0.34, 95% CI: 0.15–0.78, p = 0.01) were found to be associated with improved survival. Conclusions These findings demonstrate that CTLA-4, PD-1, PDL-1, and TIM-3 were highly expressed in TNBC. Based on these high expression patterns, further studies directed towards combined therapies are warranted in advanced TNBC in future.


2018 ◽  
Vol 1 (1) ◽  
pp. 1-9
Author(s):  
Ade Permana ◽  
Benny Kusuma ◽  
Nur Qodir ◽  
Legiran

Introduction. CD4+ T-helper has an important role in immune system modulation especially to maintain long-term anti tumor effect. CD4+ also serves to activate CD8+ for destroyed the tumor cells. It was expected there were role of immunity on tumor growth and response of breast cancer chemotherapy to CD4+ levels serum. Furthermore, this study was aimed to investigate the effects of neoadjuvant chemotherapy on CD4+ levels in patients with locally advanced breast cancer at General Hospital Dr. Mohammad Hoesin Palembang. Method. This study was a non-comparable clinical trial by looking at serum CD4+ levels in patients with locally advanced breast cancer before and after neoadjuvant chemotherapy.   Results. Of the 30 subjects the subject age ranged from 33-66 years with an average of 45 years. There were 17 patients with contraception history (56.7%), 13 patients with family history of breast cancer (43.3%). From this study, it was obtained 23 patients with good chemotherapy response (76.7%) and there were 7 patients who had poor chemotherapy response after neoadjuvan chemotherapy (23.3%). Paired t-test analysis showed that there was a significant difference in mean CD4+ count before and after neoadjuvan chemotherapy. At the CD4+ level before chemotherapy 775.55 had a sensitivity of 60% and a specificity of 57% (cut of point). While CD4+ levels after chemotherapy 470.85 with sensitivity of 60% and specificity of 57%.   Conclusion. CD4+ pre-chemotherapy examination had a sensitivity score of 60% and a specificity of 57% in predicting neoadjuvant chemotherapy response.    


Author(s):  
Kamal Basri Siregar ◽  
Tjakra Wibawa Manuaba ◽  
Muhammad Nadjib Dahlan Lubis ◽  
Rosita Juwita Sembiring

  Objectives: This study will examine the expression of caspase-3 and apoptotic index (AI) in triple negative breast cancer (TNBC). By knowing the non-responsiveness effect earlier, adverse effects of chemotherapy can be avoided.Methods: This prospective cohort study has been approved by the local Ethics Committee. A total of 60 consent TNBC patients from Haji Adam Malik General Hospital and Bunda Thamrin Hospital were included in the study. Patients with heart, kidney, liver disease, history of surgery, chemotherapy, or hormonal therapy were excluded. Samples were analyzed immunohistochemically by monoclonal antibodies to assess caspase 3 and AI. Clinical chemotherapy response is determined as a positive or negative response based on Response Evaluation Criteria in Solid Tumors.Results: The results of this study indicated that caspase 3 was increased post-chemotherapy but could not predict the clinical response of chemotherapy. Caspase-3 post-chemotherapy (5.27±1.27 pg/mL) compared to pre-chemotherapy (4.60±1.09 pg/mL) increased significantly (p=0.003) by 0.67±1.66 pg/mL but no difference was found in AI score (p=0.819). Neither caspase 3 nor the AI were associated with a clinical chemotherapy response (p=0.514 and p=0.993, subsequently).Conclusion: Further research with larger samples is needed to determine the role and pathway of chemotherapy induced caspase 3 rise.


2019 ◽  
Vol 5 (suppl) ◽  
pp. 119-119
Author(s):  
Seung Pil Jung ◽  
Soo Youn Bae ◽  
Jeong Hyeon Lee ◽  
Joung Won Bae

119 Background: Triple negative breast cancer (TNBC) exhibits a higher rate of early recurrence and more aggressive behavior. Despite unfavorable prognoses, TNBCs are known to be highly reactive to chemotherapy and show higher pathologic complete response rates after neoadjuvant chemotherapy. However, TNBC patients with residual cancer have significantly worse prognoses than patients with non-TNBC associated residual cancer. TP53 mutations are the most common genetic alterations in breast cancer and are highly linked to basal subtype carcinomas. Past studies have investigated if TP53 mutation can predict the response of cancer to chemotherapy or affect a difference in prognosis; however, the lack of consistent results has hampered clinical applications. Because immunostaining studies can be easily performed, those results may be more useful until Next generation sequencing results are clinically applicable. The aim of this study was to determine whether p53 expression in TNBC could predict the response to neoadjuvant chemotherapy and the resulting prognosis. Methods: From 2009 to 2017, TNBC patients who underwent neoadjuvant chemotherapy were reviewed, including a total of 31 TNBC patients who had clinical lymph node metastasis. The status of p53 expression in patients before and after chemotherapy was evaluated. Results: Two patients (22.2%, 2/9) achieved pCR in p53(+) TNBC and four patients (50%, 5/10) achieved pCR in p53(-) TNBC. There was no correlation between pCR rate and p53 expression ( P= 0.350). Based on pre-chemotherapy p53 expression, there was no significant difference in DFS between p53(+) TNBC and p53(-) TNBC ( P= 0.335) . However, after chemotherapy, p53(+) TNBC had shown higher DFS than p53(-) TBNC ( P= 0.099). Based on pre-chemotherapy p53 expression, p53(+) TNBC had better OS than p53(-) TNBC, but the difference was not statistically significant ( P= 0.082). After chemotherapy, p53(+) TNBC showed significantly better OS than p53(-) TNBC ( P = 0.018). Conclusions: Immunohistochemically detected p53 expression in TNBC could not predict the response to neoadjuvant chemotherapy. However, p53 (+) TNBC had a better OS than p53 (-) TNBC in patients who underwent neoadjuvant chemotherapy.


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