Neoadjuvant chemotherapy-induced decrease of prognostic nutrition index predicts poor prognosis in patients with breast cancer.
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ABSTRACT:
SUBMITTER: Oba T
PROVIDER: S-EPMC7045374 | biostudies-literature | 2020 Feb
REPOSITORIES: biostudies-literature
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Neoadjuvant chemotherapy-induced decrease of prognostic nutrition index predicts poor prognosis in patients with breast cancer.
Oba Takaaki T Maeno Kazuma K Takekoshi Daiya D Ono Mayu M Ito Tokiko T Kanai Toshiharu T Ito Ken-Ichi KI
BMC cancer 20200227 1
<h4>Background</h4>The prognostic nutritional index (PNI), which is an easily calculated nutritional index, is significantly associated with patient outcomes in various solid malignancies. This study aimed to evaluate the prognostic impact of PNI changes in patients with breast cancer undergoing neoadjuvant chemotherapy (NAC).<h4>Methods</h4>We reviewed patients with breast cancer who underwent NAC and a subsequent surgery for breast cancer between 2005 and 2016. PNI before and after NAC were ca ...[more]
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Project description:BackgroundThe skeletal muscle index (SMI), which is calculated as the ratio of skeletal muscle area at the third lumbar vertebral level divided by height squared, has been considered a prognostic factor in patients with breast cancer. However, the prognostic impact of changes in SMI during treatment remains unclear. This study aimed to evaluate the influence of SMI changes in patients with breast cancer undergoing neoadjuvant chemotherapy (NAC).MethodsWe reviewed patients with breast cancer who underwent NAC and subsequent surgery for breast cancer between 2010 and 2017. The rate of SMI change during NAC was calculated, and the association between SMI changes and prognosis was retrospectively analyzed.ResultsIn total, 141 patients were evaluated. 48 (34.0%), 53 (37.6%), and 40 (28.4%) patients exhibited increased (≥ 3%), maintained (- 3% <, < 3%), and decreased (- 3% ≥) SMI during NAC, respectively. The decreased SMI group showed significantly poorer disease-free survival than the maintained and increased SMI groups (hazard ratio [HR] 8.29, p < 0.001 for the decreased vs. increased SMI groups; HR 3.49, p < 0.001 for the decreased vs. maintained SMI groups). Moreover, decreased SMI was an independent risk factor for disease-free survival in multivariate analysis (HR 3.68, p < 0.01).ConclusionsSkeletal muscle loss during NAC predicts poor prognosis. Our results underscore the importance of monitoring and maintaining skeletal muscle mass during NAC.
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Project description:ObjectiveThis study aims at investigating the potential prognostic significance of the breast immune prognostic index (BIPI) in breast cancer patients who received neoadjuvant chemotherapy (NACT).MethodsThe optimal cutoff value was calculated through the receiver operating characteristic curve (ROC). The correlations between BIPI and clinicopathologic characteristics were determined by the chi-square test or Fisher's exact test. The Kaplan-Meier method was used to estimate the survival probability, and the log-rank test was used to analyze the differences in the survival probability among patients. The univariate and multivariate Cox proportional hazard regression model was used to screen the independent prognostic factors. A prognostic nomogram for disease-free survival (DFS) and overall survival (OS) was built on the basis of the multivariate analyses. Furthermore, the calibration curve and decision curve analysis (DCA) were used to assess the predictive performance of the nomogram.ResultsAll enrolled patients were split into three subgroups based on the BIPI score. The mean DFS and OS of the BIPI score 0 group and BIPI score 1 group were significantly longer than those of the BIPI score 2 group (42.02 vs. 38.61 vs. 26.01 months, 77.61 vs. 71.83 vs. 53.15 months; p < 0.05). Univariate and multivariate analyses indicated that BIPI was an independent prognostic factor for patients' DFS and OS (DFS, hazard ratio (HR): 6.720, 95% confidence interval (CI): 1.629-27.717; OS, HR: 8.006, 95% CI: 1.638-39.119). A nomogram with a C-index of 0.873 (95% CI: 0.779-0.966) and 0.801 (95% CI: 0.702-0.901) had a favorable performance for predicting DFS and OS survival rates for clinical use by combining immune scores with other clinical features. The calibration curves at 1-, 3-, and 5-year survival suggested a good consistency between the predicted and actual DFS and OS probability. The DCA demonstrated that the constructed nomogram had better clinical predictive usefulness than only BIPI in predictive clinical applications of 5-year DFS and OS prognostic assessments.ConclusionsThe patients with low BIPI score have better prognoses and longer DFS and OS. Furthermore, the BIPI-based nomogram may serve as a convenient prognostic tool for breast cancer and help in clinical decision-making.
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2012-03-20 | E-GEOD-32646 | biostudies-arrayexpress
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| S-ECPF-GEOD-32646 | biostudies-other
Project description:The purpose of the present study was to investigate the association of glutathione S-transferase P1 (GSTP1) expression with resistance to neoadjuvant paclitaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide (P-FEC) in human breast cancers. The relationship of GSTP1 expression and GSTP1 promoter hypermethylation with intrinsic subtypes was also investigated. In this study, primary breast cancer patients (n = 123, stage II-III) treated with neoadjuvant P-FEC were analyzed. Tumor samples were obtained by vacuum-assisted core biopsy before P-FEC. GSTP1 expression was determined using immunohistochemistry, GSTP1 promoter methylation index (MI) using bisulfite methylation assay and intrinsic subtypes using DNA microarray. The pathological complete response (pCR) rate was significantly higher in GSTP1-negative tumors (80.0%) than GSTP1-positive tumors (30.6%) (P = 0.009) among estrogen receptor (ER)-negative tumors but not among ER-positive tumors (P = 0.267). Multivariate analysis showed that GSTP1 was the only predictive factor for pCR (P = 0.013) among ER-negative tumors. Luminal A, luminal B and HER2-enriched tumors showed a significantly lower GSTP1 positivity than basal-like tumors (P = 0.002, P < 0.001 and P = 0.009, respectively), while luminal A, luminal B and HER2-enriched tumors showed a higher GSTP1 MI than basal-like tumors (P = 0.076, P < 0.001 and P < 0.001, respectively). In conclusion, these results suggest the possibility that GSTP1 expression can predict pathological response to P-FEC in ER-negative tumors but not in ER-positive tumors. Additionally, GSTP1 promoter hypermethylation might be implicated more importantly in the pathogenesis of luminal A, luminal B and HER2-enriched tumors than basal-like tumors.
2012-03-20 | GSE32646 | GEO
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Project description:BackgroundNeoadjuvant chemotherapy is a key component of breast cancer treatment regimens and pathologic complete response to this therapy varies among patients. This is presumably due to differences in the molecular mechanisms that underlie each tumor's disease pathology. Developing genomic clinical assays that accurately categorize responders from non-responders can provide patients with the most effective therapy for their individual disease.MethodsWe applied our previously developed E2F4 genomic signature to predict neoadjuvant chemotherapy response in breast cancer. E2F4 individual regulatory activity scores were calculated for 1129 patient samples across 5 independent breast cancer neoadjuvant chemotherapy datasets. Accuracy of the E2F4 signature in predicting neoadjuvant chemotherapy response was compared to that of the Oncotype DX and MammaPrint predictive signatures.ResultsIn all datasets, E2F4 activity level was an accurate predictor of neoadjuvant chemotherapy response, with high E2F4 scores predictive of achieving pathologic complete response and low scores predictive of residual disease. These results remained significant even after stratifying patients by estrogen receptor (ER) status, tumor stage, and breast cancer molecular subtypes. Compared to the Oncotype DX and MammaPrint signatures, our E2F4 signature achieved similar performance in predicting neoadjuvant chemotherapy response, though all signatures performed better in ER+ tumors compared to ER- ones. The accuracy of our signature was reproducible across datasets and was maintained when refined from a 199-gene signature down to a clinic-friendly 33-gene panel.ConclusionOverall, we show that our E2F4 signature is accurate in predicting patient response to neoadjuvant chemotherapy. As this signature is more refined and comparable in performance to other clinically available gene expression assays in the prediction of neoadjuvant chemotherapy response, it should be considered when evaluating potential treatment options.
| S-EPMC5414335 | biostudies-literature
Project description:Pathologic complete response (pCR) prediction after neoadjuvant chemotherapy (NAC) is important for clinical decision-making in breast cancer. This study investigated the predictive value of Nottingham prognostic index (NPI), Immunohistochemical four (IHC4) score and a new predictive index combined with them in estrogen-positive (ER+) breast cancer following NAC. We retrospectively gathered clinical data of 739 ER+ breast cancer patients who received NAC from two cancer centers. We developed a new predictive biomarker named NPI+IHC4 to predict pCR in ER+ breast cancer in a training set (n=443) and validated it in an external validation set (n=296). The results showed that a lower IHC4 score, NPI and NPI+IHC4 were significantly associated a high pCR rate in the entire cohort. In the study set, NPI+IHC4 showed a better sensitivity and specificity for pCR prediction (AUC 0.699, 95% CI 0.626-0.772) than IHC4 score (AUC 0.613, 95% CI 0.533-0.692), NPI (AUC 0.576, 95% CI 0.494-0.659), tumor size (AUC 0.556, 95% CI 0.481-0.631) and TNM stage (AUC 0.521, 95% CI 0.442-0.601). In the validation set, NPI+IHC4 had a better predictive value for pCR (AUC 0.665, 95% CI 0.579-0.751) than IHC4 score or NPI alone. In addition, ER+ patients with lower IHC4, NPI and NPI+IHC4 scores had significantly better DFS in both study and validation sets. In summary, NPI+IHC4 can predict pCR following NAC and prognosis in ER+ breast cancer, which is cost-effect and potentially more useful in guiding decision-making regarding NAC in clinical practice. Further validation is needed in prospective clinical trials with larger cohorts of patients.
| S-EPMC5349990 | biostudies-literature
Project description:BackgroundNeoadjuvant chemotherapy (NAC) is the standard therapeutic strategy for triple-negative breast cancer (TNBC). TNBC patients with residual disease after NAC have a significantly worse survival than those with pathological complete response (pCR); however, there is no apparent prognostic factor for non-pCR patients. Cancer stemness or epithelial-mesenchymal transition (EMT) might influence the sensitivity to chemotherapy.Patients and methodsForty-eight patients with TNBC who were treated with NAC were available were included in this study. The expressions of stemness marker CD44v9, EMT marker vimentin and BRCA1, and basal phenotype were evaluated with immunohistochemistry. The relationships between the expression of these proteins and the pCR rate and the prognosis, especially in the patients with residual tumors, were investigated.ResultsAmong the 48 patients, pCR was achieved in 14 cases. High nuclear grade and basal phenotype in the pre-NAC samples were significantly correlated with pCR (p = 0.0458 and 0.0343). There were no significant relationships between the pCR rate and the expression of CD44v9, vimentin, or BRCA1. Achieving pCR was significantly correlated with longer distant metastasis-free survival (DMFS) (p = 0.0206). High CD44v9 expression was significantly associated with shorter DMFS (p = 0.0291). Among the patients in whom pCR was not achieved, high grade in the residual tumor cells, poor pathological response and high CD44v9 expression in the pre-treatment CNB samples were significantly correlated with a poor DMFS (p = 0.0433, 0.0406 and p = 0.0333). In addition, high grade in the residual tumor cells was significantly associated with high CD44v9 expression in the pre-treatment CNB (p = 0.0389).ConclusionsHigh CD44v9 expression in pre-NAC samples was associated with poor prognosis in TNBC patients treated with NAC, especially for those in whom pCR was not achieved.
| S-EPMC6314992 | biostudies-literature
Project description:ObjectivePrognostic nutritional index (PNI), calculated as serum albumin (ALB) (g/L) + 5 × total lymphocyte count (109/L), is initially used to evaluate nutritional status in patients undergoing surgery and may evaluate the therapeutic effects and predict the survival of various solid tumors. The present study aimed to evaluate the potential prognostic significance of PNI in breast cancer patients receiving neoadjuvant chemotherapy (NACT).MethodsA total of 785 breast cancer patients treated with neoadjuvant chemotherapy were enrolled in this retrospective study. The optimal cutoff value of PNI by receiver operating characteristic curve stratified patients into a low-PNI group (<51) and a high PNI group (≥51). The associations between breast cancer and clinicopathological variables by PNI were determined by chi-square test or Fisher's exact test. Kaplan-Meier plots and log-rank test were used to evaluate the clinical outcomes of disease-free survival (DFS) and overall survival (OS). The prognostic value of PNI was analyzed by univariate and multivariate Cox proportional hazards regression models. The toxicity of NACT was accessed by the National Cancer Institute Common Toxicity Criteria (NCI-CTC).ResultsThe results indicated that PNI had prognostic significance by an optimal cutoff value of 51 on DFS and OS in univariate and multivariate Cox regression survival analyses. Breast cancer patients with a high PNI value had longer DFS and OS than those with a low PNI value [47.64 vs. 36.60 months, P < 0.0001, hazard ratio (HR) = 0.264, 95%CI = 0.160-0.435; 73.61 vs. 64.97 months, P < 0.0001, HR = 0.319, 95%CI = 0.207-0.491, respectively]. Furthermore, the results indicated that patients with high PNI had longer DFS and OS than those with low PNI in early stage and advanced breast cancer, especially in advanced breast cancer. The mean DFS and OS times for breast cancer patients with high PNI by the log-rank test were longer than in those with low PNI in different molecular subtypes. Moreover, the mean DFS and OS times in patients with high PNI by the log-rank test were longer than in those patients with low PNI without or with lymph vessel invasion. The common toxicities after neoadjuvant chemotherapy were hematologic and gastrointestinal reaction, and the PNI had no significance on the toxicities of all enrolled patients, except in anemia, leukopenia, and myelosuppression.ConclusionPretreatment PNI with the advantages of being convenient, noninvasive, and reproducible was a useful prognostic indicator for breast cancer patients receiving neoadjuvant chemotherapy and is a promising biomarker for breast cancer on treatment strategy decisions.
| S-EPMC8042235 | biostudies-literature