• Title, Summary, Keyword: pathological response

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Response of Triple Negative Breast Cancer to Neoadjuvant Chemotherapy: Correlation between Ki-67 Expression and Pathological Response

  • Elnemr, Gamal M;El-Rashidy, Ahmed H;Osman, Ahmed H;Issa, Lotfi F;Abbas, Osama A;Al-Zahrani, Abdullah S;El-Seman, Sheriff M;Mohammed, Amrallah A;Hassan, Abdelghani A
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.2
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    • pp.807-813
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    • 2016
  • Triple-negative breast cancers constitute about 15% of all cases, but despite their higher response to neoadjuvant chemotherapy, the tumors are very aggressive and associated with a poor prognosis as well as a higher risk of early recurrence. This study was retrospectively performed on 101 patients with stage II and III invasive breast cancer who received 6-8 cycles of neo-adjuvant chemotherapy. Out of the total, 23 were in the triple negative breast cancer subgroup. Nuclear Ki-67 expression in both the large cohort group (n=101) and triple negative breast cancer subgroup (n=23) and its relation to the pathological response were evaluated. The purpose of the study was to identify the predictive value of nuclear protein Ki-67 expression among patients with invasive breast cancers, involving the triple negative breast cancer subgroup, treated with neoadjuvant chemotherapy in correlation to the rate of pathological complete response. The proliferation marker Ki-67 expression was highest in the triple negative breast cancer subgroup. No appreciable difference in the rate of Ki-67 expression in triple negative breast cancer subgroup using either a cutoff of 14% or 35%. Triple negative breast cancer subgroup showed lower rates of pathological complete response. Achievement of pathological complete response was significantly correlated with smaller tumor size and higher Ki-67 expression. The majority of triple negative breast cancer cases achieved pathological partial response. The study concluded that Ki-67 is a useful tool to predict chemosensitivity in the setting of neoadjuvant chemotherapy for invasive breast cancer but not for the triple negative breast cancer subgroup.

Predictive Value of IHC4 Score for Pathological Response to Neoadjuvant Chemotherapy in Hormone Receptor-Positive Breast Cancer

  • Elsamany, Shereef;Elmorsy, Soha;Alzahrani, Abdullah;Rasmy, Ayman;Abozeed, Waleed N;Mohammed, Amrallah A;Sherisher, Mohamed A;Abbas, Mohammed M;Mashhour, Miral
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.17
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    • pp.7975-7979
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    • 2015
  • Purpose: This study aimed to explore the value of IHC4 in predicting pathological response after neoadjuvant chemotherapy in patients with hormonal receptor (HR)-positive breast cancer (BC). Materials and Methods: In this retrospective exploratory study, data for 68 HR-positive BC patients who received neoadjuvant chemotherapy were recorded. IHC4 scores were calculated based on estrogen receptors/progesterone receptors, Ki-67 and HER2 status. Logistic and ordinal regression analyses in addition to likelihood ratio test were used to explore associations of IHC4 scores and other clinico-pathological parameters with pathological complete response (pCR) and pathological stage. Results: Taking the 25th percentile as the cut-off, a lower IHC4 score was associated with an increased probability of pCR (low; 52.9% vs. High; 21.6%, OR=4.1, 95% CI=1.28-13.16, p=0.018) and a lower pathological stage (OR=3.9, 95% CI=1.34-11.33, p=0.012). When the IHC4 score was treated as a continuous variable, a lower score was again associated with an increased probability of pCR (OR=1.010, 95% CI=1.001-1.018, p=0.025) and lower pathological stage (OR=1.009, 95% CI=1.002-1.017, P=0.008). Lower clinical stage was associated with a better pCR rate that was of borderline significance (P=0.056). When clinical stage and IHC4 score were incorporated together in a logistic model, the likelihood ratio test gave a P-value of 0.004 after removal of the IHC4 score and 0.011 after removal of the stage, indicating a more significant predictive value of the IHC4 score for pCR. Conclusions: This study suggests that the IHC4 score can predict pathological response to neoadjuvant chemotherapy in HR-positive BC patients. This finding now needs to be validated in a larger cohort of patients.

Single nucleotide polymorphism of GSTP1 and pathological complete response in locally advanced rectal cancer patients treated with neoadjuvant concomitant radiochemotherapy

  • Nicosia, Luca;Gentile, Giovanna;Reverberi, Chiara;Minniti, Giuseppe;Valeriani, Maurizio;de Sanctis, Vitaliana;Marinelli, Luca;Cipolla, Fabiola;de Luca, Ottavia;Simmaco, Maurizio;Osti, Mattia F.
    • Radiation Oncology Journal
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    • v.36 no.3
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    • pp.218-226
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    • 2018
  • Purpose: Standard treatment for locally advanced rectal cancer consists of neoadjuvant radiochemotherapy with concomitant fluoropyrimidine or oxaliplatin and surgery with curative intent. Pathological complete response has shown to be predictive for better outcome and survival; nevertheless there are no biological or genetic factors predictive for response to treatment. We explored the correlation between the single nucleotide polymorphisms (SNPs) GSTP1 (A313G) and XRCC1 (G28152A), and the pathological complete response and survival after neoadjuvant radiochemotherapy in locally advanced rectal cancer patients. Materials and Methods: Genotypes GSTP1 (A313G) and XRCC1 (G28152A) were determined by pyrosequencing technology in 80 patients affected by locally advanced rectal cancer. Results: The overall rate of pathological complete response in our study population was 18.75%. Patients homozygous AA for GSTP1 (A313G) presented a rate of pathological complete response of 26.6% as compared to 8.5% of the AG+GG population (p = 0.04). The heterozygous comparison (AA vs. AG) showed a significant difference in the rate of pathological complete response (26.6% vs. 6.8%; p = 0.034). GSTP1 AA+AG patients presented a 5- and 8-year cancer-specific survival longer than GSTP1 GG patients (87.7% and 83.3% vs. 44.4% and 44.4%, respectively) (p = 0.014). Overall survival showed only a trend toward significance in favor of the haplotypes GSTP1 AA+AG. No significant correlations were found for XRCC1 (G28152A). Conclusion: Our results suggest that GSTP1 (A313G) may predict a higher rate of pathological complete response after neoadjuvant radiochemotherapy and a better outcome, and should be considered in a more extensive analysis with the aim of personalization of radiation treatment.

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;Aryandono, Teguh
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.2
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    • pp.595-598
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    • 2014
  • 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.

Evaluation of Response to Preoperative Chemotherapy Versus Surgery Alone in Gastroesophageal Cancer: Tumor Resectability, Pathologic Results and Post-Operative Complications

  • Marandi, Aref Kashefi;Shojaiefard, Abolfazl;Soroush, Ahmadreza;Abdegah, Ali Ghorbani;Jafari, Mehdi;Khodadost, Mahmoud;Mahmoudzade, Hossein
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.sup3
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    • pp.231-237
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    • 2016
  • Gastroesophageal cancer is one of the most common types of cancer worldwide. Despite significant developments in management, 5-year survival in the developing world is less than 20 percent. Due to restricted research about the impact of preoperative chemotherapy (POC) on tumor resection, pathological response and postoperative complications in Iran, we designed and implemented the present retrospective cross- sectional study on 156 patients with gastroesophageal cancer (GEc) between 2013 and 2015 at Shariati Hospital of Tehran. Two groups were included, the first group had previously received preoperative chemotherapy and the second group had only undergone surgery. All patients were followed for at least one year after the operation in terms of tumor recurrence, relapse free survival and one-year survival. The two groups were eventually compared regarding tumor resection, pathological response, postoperative complications, recurrence rate and survival. The mean age was $66.5{\pm}7.3years$ and 78 percent were male. The tumor resectability, pathological response and postoperative complications in the group which received POC were 93.5%, 21.8% and 12.8%, respectively, and in the surgery alone group figures for tumor resection and postoperative complications were 76% and 29.5%, respectively. Also based on our study the 5-year survival in the POC group was better (79.5% vs. 66.5%). Using standard neoadjuvant regimens (preoperative chemotherapy/chemoradiotherapy) beforesurgery could increase tumor resectability, pathological response, and improve the general status of the patients. Therefore using POC may be recommended over surgery alone.

Predictive Value of the Pattern of β-Catenin Expression for Pathological Response to Neoadjuvant Chemotherapy in Breast Cancer Patients

  • Elsamany, S;Elemam, O;Elmorsy, S;Alzahrani, A;Abbas, MM
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.8
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    • pp.4089-4093
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    • 2016
  • Purpose: This study aimed to explore the association of ${\beta}-catenin$ expression pattern with pathological response after neoadjuvant chemotherapy in breast cancer (BC) patients. Materials and Methods: In this retrospective exploratory study, data for 50 BC patients who received neoadjuvant chemotherapy were recorded. ${\beta}-catenin$ expression in tumours was assessed using immunohistochemistry and classified as either membranous or cytoplasmic according to the pattern of staining. Distributions of different clinico-pathological parameters according to ${\beta}-catenin$ expression were assessed using the Chi-square test. Logistic regression analysis was used to assess any relation of the pattern of ${\beta}-catenin$ expression with the pathological response. Results: Cytoplasmic ${\beta}-catenin$ expression was detected in 34% of BCs. Among our cases, 52% were hormonal receptor (HR)-positive, 24% were HER2-positive, 74% were clinical stage III and 74% received both anthracycline and taxane-based chemotherapy. Patients with cytoplasmic expression were more commonly younger than 40 years at diagnosis (cytoplasmic, 41.2% vs. no cytoplasmic expression, 12.1%, p=0.03). By doing t-test, cytoplasmic ${\beta}-catenin$ expression was linked with a higher body mass index compared to membranous-only expression ($mean{\pm}SD$ $33.0{\pm}4.47$ vs. $29.6{\pm}6.01$, respectively, p=0.046). No significant associations were found between ${\beta}-catenin$ expression and other parameters such as HR and HER2 status, or clinical stage. Complete pathological response (pCR) rate was twice as great in patients with membranous expression but without statistical significance (membranous-only, 33.3% vs. cytoplasmic, 17.6%, OR= 2.3, 95% CI= 0.55-9.87, p=0.24). Conclusions: This study suggests that cytoplasmic ${\beta}-catenin$ expression may be linked with lower probability of achieving pCR after neoadjuvant chemotherapy. These data need to be validated in a larger cohort of patients.

Treatment outcomes of neoadjuvant concurrent chemoradiotherapy followed by esophagectomy for patients with esophageal cancer

  • Kim, Yong-Hyub;Song, Sang-Yun;Shim, Hyun-Jeong;Chung, Woong-Ki;Ahn, Sung-Ja;Yoon, Mee Sun;Jeong, Jae-Uk;Song, Ju-Young;Nam, Taek-Keun
    • Radiation Oncology Journal
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    • v.33 no.1
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    • pp.12-20
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    • 2015
  • Purpose: To evaluate treatment outcomes and determine prognostic factors in patients with esophageal cancer treated with esophagectomy after neoadjuvant chemoradiotherapy (NCRT) Materials and Methods: We retrospectively evaluated 39 patients with esophageal cancer who underwent concurrent chemoradiotherapy followed by esophagectomy between 2002 and 2012. Initial clinical stages of patients were stage IB in 1 patient (2.6%), stage II in 5 patients (12.9%), and stage III in 33 patients (84.6%). Results: The median age of all the patients was 62 years, and the median follow-up period was 17 months. The 3-year overall survival (OS) rate was 33.6% in all the patients. The 3-year locoregional recurrence-free survival (LRFS) rate was 33.7%. In multivariate analysis with covariates of age, the Eastern Cooperative Oncology Group performance status, hypertension, diabetes mellitus, tumor length, clinical response, clinical stage, pathological response, pathological stage, lymphovascular invasion, surgical type, and radiotherapy to surgery interval, only pathological stage was an independent significant prognostic factor affecting both OS and LRFS. The complications in postoperative day 90 were pneumonia in 9 patients, anastomotic site leakage in 3 patients, and anastomotic site stricture in 2 patients. Postoperative 30-day mortality rate was 10.3% (4/39); the cause of death among these 4 patients was respiratory failure in 3 patients and myocardial infarction in one patient. Conclusion: Only pathological stage was an independent prognostic factor for both OS and LRFS in patients with esophageal cancer treated with esophagectomy after NCRT. We could confirm the significant role of NCRT in downstaging the initial tumor bulk and thus resulting in better survival of patients who gained earlier pathological stage after NCRT.

Immunosignature: Serum Antibody Profiling for Cancer Diagnostics

  • Chapoval, Andrei I;Legutki, J Bart;Stafford, Philip;Trebukhov, Andrey V;Johnston, Stephen A;Shoikhet, Yakov N;Lazarev, Alexander F
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.12
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    • pp.4833-4837
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    • 2015
  • Biomarkers for preclinical diagnosis of cancer are valuable tools for detection of malignant tumors at early stages in groups at risk and screening healthy people, as well as monitoring disease recurrence after treatment of cancer. However the complexity of the body's response to the pathological processes makes it virtually impossible to evaluate this response to the development of the disease using a single biomarker that is present in the serum at low concentrations. An alternative approach to standard biomarker analysis is called immunosignature. Instead of going after biomarkers themselves this approach rely on the analysis of the humoral immune response to molecular changes associated with the development of pathological processes. It is known that antibodies are produced in response to proteins expressed during cancer development. Accordingly, the changes in antibody repertoire associated with tumor growth can serve as biomarkers of cancer. Immunosignature is a highly sensitive method for antibody repertoire analysis utilizing high density peptide microarrays. In the present review we discuss modern methods for antibody detection, as well as describe the principles and applications of immunosignature in research and clinical practice.

Carbohydrate Antigen 19-9 Levels Associated with Pathological Responses to Preoperative Chemoradiotherapy in Rectal Cancer

  • Yeo, Seung-Gu;Kim, Dae Yong;Kim, Tae Hyun;Kim, Sun Young;Baek, Ji Yeon;Chang, Hee Jin;Park, Ji Won;Oh, Jae Hwan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.13
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    • pp.5383-5387
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    • 2014
  • Purpose: To investigate whether pretreatment serum carbohydrate antigen 19-9 (CA 19-9) levels are associated with pathological responses to preoperative chemoradiotherapy (CRT) in patients with rectal cancer. Materials and Methods: In total, 260 patients with locally advanced rectal cancer (cT3-4NanyM0) who underwent preoperative CRT and radical surgery were analyzed retrospectively. CRT consisted of 50.4 Gy pelvic radiotherapy and concurrent chemotherapy. Radical surgery was performed at a median of 7 weeks after CRT completion. Pathological CRT response criteria included downstaging (ypStage 0-I) and ypT0-1. A discrimination threshold of CA 19-9 level was determined using a receiver operating characteristics analysis. Results: The median CA 19-9 level was 8.0 (1.0-648.0) U/mL. Downstaging occurred in 94 (36.2%) patients and ypT0-1 in 50 (19.2%). The calculated optimal threshold CA 19-9 level was 10.2 U/mL for downstaging and 9.0 U/mL for ypT0-1. On multivariate analysis, CA 19-9 (${\leq}9.0U/mL$) was significantly associated with downstaging (odds ratio, 2.089; 95% confidence interval, 1.189-3.669; P=0.010) or ypT0-1 (OR, 2.207; 95%CI, 1.079-4.512; P=0.030), independent of clinical stage or carcinoembryonic antigen. Conclusions: This study firstly showed a significant association of pretreatment serum CA 19-9 levels with pathological CRT responses of rectal cancer. The CA 19-9 level is suggested to be valuable in predicting CRT responses of rectal cancer cases before treatment.

A Comparative Study on Responses to the Sasang Constitution Questionnaire for Patients between Korean and Japanese (한국인과 일본인의 환자용 사상체질 설문지 문항 응답 비교 연구)

  • Ryu, Dong-Hoon;Jeong, Jong-Hoon;Bae, U-Yeol;Kim, Kyu-Kon;Jeon, Soo-Hyung;Kim, Jong-Won
    • Journal of Sasang Constitutional Medicine
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    • v.25 no.3
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    • pp.167-179
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    • 2013
  • Objectives This study was performed to compare responses of Korean to the Sasang Constitution questionnaire with those of Japanese and to learn difference in characteristic according to the Sasang Constitution between two countries. Methods 301 Korean visiting the department of the Sasang Constitution, Dong-Eui Medical Center in Busan, Korea from November 2006 to September 2010 responded to the SSCQ-P(Sasang Constitution Questionnaire for Patients). Sasang Constitution specialist interviewed subjects and diagnosed their Sasang Constitution. 361 Japanese visiting the center for Kampo Medicine, Keio University in Tokyo, Japan from January 2010 to February 2011 responded the SSCQ-J(Sasang Constitution Questionnaire for Japanese). The Sasang Constitution was diagnosed in the same way as Korean. We compare responses to the SSCQ-P in Korean with those to the SSCQ-J in Japanese. Results 1. Among Soyangin related 58 items of Sasang Constitution questionnaire, 26, 46.36% items had statistically significant response results in both Korean and Japanese and response disposition of all these items was same. Among Taeeumin related 68items, 36, 52.94% items had statistically significant response results in both Korean and Japanese. Of these, response disposition of 35 items was same and that of 1 item was different. Among Soeumin related 71 items, 31, 43.66% items had statistically significant response results in both Korean and Japanese. Of these, response disposition of 28 items was same and that of 3 items was different. 2. The proportion of items having statistical significance and same disposition in both Korean and Japanese by Sasang Constitutional characteristic category[Features and Way of Speaking, Physical Appearance, Temperament and Talent, Pathological Syndromes] was as follows; In Soyangin, the proportion in Pathological Syndromes was 27.8% and that in the others was more than 41.7%. In Taeeumin, the proportion in Pathological Syndromes was 33.3% and that in the others was more than 57.9%. In Soeumin, the proportion in Features and Way of Speaking was 70.6%, that in Physical Appearance was 8.3% and that in the others was 30~40%. Conclusions The response disposition of many of items having statistical significance between Korean and Japanese was same and that of a few was different. From this, there are many common Sasang Constitutional characteristics between two countries, and possibility of applying the Sasang Constitutional Medicine of Korea to Japan.