Oestrogen receptor status, pathological complete response and prognosis in patients receiving neoadjuvant chemotherapy for early breast cancer.
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ABSTRACT:
SUBMITTER: Ring AE
PROVIDER: S-EPMC2409783 | biostudies-other | 2004 Dec
REPOSITORIES: biostudies-other
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Project description:In the neoadjuvant setting, changes in the proliferation marker Ki67 are associated with primary endocrine treatment efficacy, but its value as a predictor of response to chemotherapy is still controversial.We analyzed 262 patients with centralized basal Ki67 immunohistochemical evaluation derived from 4 GEICAM (Spanish Breast Cancer Group) clinical trials of neoadjuvant chemotherapy for breast cancer. The objective was to identify the optimal threshold for Ki67 using the receiver-operating characteristic curve method to maximize its predictive value for chemotherapy benefit. We also evaluated the predictive role of the defined Ki67 cutoffs for molecular subtypes defined by estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2).A basal Ki67 cutpoint of 50% predicted pathological complete response (pCR). Patients with Ki67 >50% achieved a pCR rate of 40% (36 of 91) versus a pCR rate of 19% in patients with Ki67 ? 50% (33 of 171) (p = .0004). Ki67 predictive value was especially relevant in ER-HER2- and ER-HER2+ patients (pCR rates of 42% and 64%, respectively, in patients with Ki67 >50% versus 15% and 45%, respectively, in patients with Ki67 ? 50%; p = .0337 and .3238, respectively). Both multivariate analyses confirmed the independent predictive value of the Ki67 cutpoint of 50%.Basal Ki67 proliferation index >50% should be considered an independent predictive factor for pCR reached after neoadjuvant chemotherapy, suggesting that cell proliferation is a phenomenon closely related to chemosensitivity. These findings could help to identify a group of patients with a potentially favorable long-term prognosis.The use of basal Ki67 status as a predictive factor of chemotherapy benefit could facilitate the identification of a patient subpopulation with high probability of achieving pathological complete response when treated with primary chemotherapy, and thus with a potentially favorable long-term prognosis.
| S-EPMC4746087 | biostudies-literature
Project description:BackgroundInflammation plays an important role in tumor proliferation, metastasis, and resistance to chemotherapy. The systemic inflammation response index (SIRI), has been reported to be closely related to prognosis in many tumors, such as breast and gastric cancers. However, the predictive value of pretreatment SIRI on pathological complete response (pCR) rates in patients with breast cancer treated with neoadjuvant chemotherapy (NAC) is unknown. This study examined the correlation between SIRI and pCR in patients with breast cancer receiving NAC and identified convenient and accurate predictive indicators for pCR.MethodsWe retrospectively analyzed the clinicopathological parameters and pretreatment peripheral blood characteristics of the 241 patients with breast cancer who received NAC between June 2015 and June 2020. Receiver operating characteristic (ROC) curves were used to determine the optimal cutoff of SIRI. ROC curves were also plotted to verify the accuracy of inflammatory markers for pCR prediction. The chi-squared test was used to explore the relationships of SIRI with pCR and other clinicopathological parameters. Multivariate analyses were performed using a logistic regression model.ResultsAmong the 241 patients, 48 (19.92%) achieved pCR. pCR was significantly related to SIRI, the neutrophil-lymphocyte ratio (NLR), the lymphocyte-monocyte ratio (LMR), molecular subtypes and other clinicopathological parameters, such as BMI, clinical T and N staging, and histological grade. Multivariate analyses indicated that the clinical T and N staging, SIRI, and NLR were independent prognostic factors for pCR in patients with breast cancer. The area under the ROC curve for SIRI was larger than that for NLR. Compared to patients with SIRI ≥0.72, patients with SIRI < 0.72 had a nearly 5-fold higher chance of obtaining pCR (odds ratio = 4.999, 95% confidence interval = 1.510-16.551, p = 0.000).ConclusionsPretreatment SIRI is predictive of pCR in patients with breast cancer receiving NAC, and the index can assist physicians in formulating personalized treatment strategies.
| S-EPMC8204500 | biostudies-literature
Project description:PURPOSE:Many patients with breast cancer still relapse after curative treatment. How to identify the ones with high relapse risk remains a critical problem. Circulating tumor DNA (ctDNA) has recently become a promising marker to monitor tumor burden. Whether ctDNA can be used to predict the response and prognosis in patients with breast cancer receiving neoadjuvant chemotherapy (NAC) is unknown. Our study aimed to evaluate the clinical value of the presence and dynamic change of ctDNA to predict the tumor response and prognosis in patients with breast cancer treated with NAC. MATERIALS AND METHODS:Fifty-two patients with early breast cancer who underwent NAC were prospectively enrolled. Serial plasma samples before, during, and after NAC and paired tumor biopsies were harvested and subjected to deep targeted sequencing using a large next-generation sequencing panel that covers 1,021 cancer-related genes. RESULTS:Positive baseline ctDNA was detected in 21 of 44 patients before NAC. Most patients with positive ctDNA had one or more mutations confirmed in paired primary tumor. The ctDNA level after 2 cycles of NAC was predictive of local tumor response after all cycles of NAC (area under the curve, 0.81; 95% CI, 0.61 to 1.00). ctDNA tracking during NAC outperformed imaging in predicting the overall response to NAC. More importantly, positive baseline ctDNA is significantly associated with worse disease-free survival (P = .011) and overall survival (P = .004) in patients with early breast cancer, especially in estrogen receptor-negative patients. CONCLUSION:Our study demonstrated that ctDNA can be used to predict tumor response to NAC and prognosis in early breast cancer, providing information to tailor an individual's therapeutic regimen.
| S-EPMC7450928 | biostudies-literature
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. Fresh frozen tumor samples obtained by vacuum-assisted core biopsy from one hundred and fifteen patients were subjected to RNA extraction and hybridization on Affymetrix microarrays.
2012-03-20 | E-GEOD-32646 | biostudies-arrayexpress
Project description:We performed a pairwise and network meta-analysis to compare pathological complete response (pCR) among neoadjuvant chemotherapy in patients with triple-negative breast cancer. We searched PubMed for randomized clinical trials between January 1, 2000 and December 1, 2020. Abstracts from meetings were also searched. A frequentist random-effect model was applied to compare pCR and toxicities. The P-score was used to rank treatment effects. Nineteen trials with 16 treatments and 7794 patients were included. On the basis of SoC, the addition of carboplatin (OR = 1.82, 95% CI, 1.24 to 2.68, P < .01) and the addition of checkpoint inhibitors (OR = 1.69, 95% CI, 1.23 to 2.32, P < .01) increased pCR in pairwise meta-analysis; compared with paclitaxel, nab-paclitaxel did not improve pCR rates (OR = 1.81, 95% CI, .80 to 4.12, P = .16). The anthracycline-sparing regimen led to similar pCR compared with the anthracycline-containing regimen (OR = 1.50, 95% CI, .82 to 2.76, P = .19). In network meta-analysis, the addition of carboplatin plus a PD-1 inhibitor (pembrolizumab), carboplatin plus bevacizumab, and carboplatin plus veliparib ranked as the top three treatments for achieving pCR, with corresponding P-scores of .91, .84, and .72, respectively. Among patients with homologous recombination deficiency, the addition of carboplatin (OR = 1.31, 95% CI, .69 to 2.50, P = .41) or carboplatin plus PARP inhibitors (OR = 1.19, 95% CI, .58 to 2.47, P = .63) did not increase pCR. For triple-negative breast cancer, combining carboplatin with taxane-anthracycline-containing neoadjuvant chemotherapy could be the standard of care, and the combination containing checkpoint inhibitor is promising. However, their role in long-term oncologic outcome remains to be determined.
| S-EPMC8606982 | biostudies-literature
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. Fresh frozen tumor samples obtained by vacuum-assisted core biopsy from one hundred and fifteen patients were subjected to RNA extraction and hybridization on Affymetrix microarrays.
| S-ECPF-GEOD-32646 | biostudies-other
Project description:PurposeTo evaluate the predictive and prognostic value of tumor-infiltrating lymphocytes (TILs) before and after neoadjuvant chemotherapy (NAC) in patients with breast cancer.Patients and methodsConsecutive breast cancer patients treated with NAC between August 2008 and November 2019 were retrospectively analyzed. TIL levels were evaluated of invasive tumor samples, and high expression was defined as TILs >10%. Total pathological complete response (pCR) was defined as no invasive tumor in the breast or lymph nodes. Univariate and multivariate analyses were used to assess factors associated with pCR rate, disease-free survival (DFS), and overall survival.ResultsA total of 461 patients were included. The mean pre-NAC TIL level was higher among patients with pCR than among patients without pCR (24.28% ± 2.34% vs. 11.34% ± 0.60%, respectively, p < 0.0001). The multivariate analysis demonstrated that a high pre-NAC TIL level was an independent risk factor for a higher pCR (odds ratio = 3.92, 95% CI = 2.23-6.90, p < 0.001). Patients with high pre-NAC TIL levels had a better 5-year DFS than those with low pre-NAC TIL levels (84.5% vs. 68.9%, HR = 0.50, 95% CI = 0.31-0.81, p = 0.005). The multivariate analysis showed that pre-NAC TIL (HR = 0.48; 95% CI = 0.29-0.81, p = 0.006) but not post-NAC TIL (HR = 0.89, 95% CI = 0.50-1.59, p = 0.699) was significantly associated with DFS among patients without pCR. Furthermore, patients with low pre- and post-NAC TIL levels had a worse 5-year DFS than those with high pre-NAC TIL levels (HR = 2.09, 95% CI = 1.23-3.56, p = 0.007).ConclusionsPre-NAC TIL level can predict pCR and DFS in patients with breast cancer receiving NAC. For patients without pCR, pre-NAC TIL, and TIL category change, but not post-NAC TIL, were significantly associated with DFS.
| S-EPMC8607245 | biostudies-literature
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
Project description:BackgroundBreast cancer with pathological non-complete response (non-pCR) after neoadjuvant chemotherapy (NAC) has a worse prognosis. Despite Neo-Bioscore has been validated as an independent prognostic model for breast cancer submitted to NAC, non-pCR carcinoma was not assessed in this setting.MethodsThis is a retrospective trial that included women with localized breast cancer who underwent NAC and had non-pCR carcinoma in surgical specimen between 01/01/2013 to 12/31/2015 with a three-year follow-up. Survival analysis was performed by Kaplan-Meier estimator and hazard ratio (HR) set by log-rank test for the primary and secondary endpoints, respectively Disease-Free Survival (DFS) and Overall Survival (OS). According to Neo-Bioscore, the proposed prognostic model named Clustered Neo-Bioscore was classified into low (0-3), low-intermediate (4-5), high-intermediate (6) and high (7) risk. The prognostic accuracy for recurrence risk was assessed by time-dependent receiver operating characteristic (time-ROC) methodology. Multivariate Cox regression assessed the menopausal status, histological grade, Ki-67, estrogen receptor, HER2, tumor subtype, pathological and clinical stages. Confidence interval at 95% (CI95%) and statistical significance at set 2-sided p-value less than 0.05 were adopted.ResultsAmong the 310 women enrolled, 267 patients (86.2%) had non-pCR carcinoma presenting size T3/T4 (63.3%), node-positive axilla (74.9%), stage III (62.9%), Ki-67???20% (71.9%) and non-luminal A (78.3%). Non-pCR carcinoma presented worse DFS-3y (HR?=?3.88, CI95%?=?1.18-11.95) but not OS-3y (HR?=?2.73, CI95%?=?0.66-11.40). Clustered Neo-Bioscore discerned the recurrence risk for non-pCR carcinoma: low (DFS-3y?=?0.86; baseline), low-intermediate (DFS-3y?=?0.70; HR?=?2.61), high-intermediate (DFS-3y?=?0.13, HR?=?14.05), and high (DFS-3y?=?not achieved; HR?=?22.19). The prognostic accuracy was similar between Clustered Neo-Bioscore and Neo-Bioscore (0.76 vs 0.78, p?>?0.05). Triple-negative subtype (HR?=?3.6, CI95%?=?1.19-10.92) and pathological stages II (HR?=?5.35, CI95%?=?1.19-24.01) and III (HR?=?6.56, CI95%?=?1.29-33.32) were prognoses for low-intermediate risk, whereas pathological stage III (HR?=?13.0, CI95%?=?1.60-106.10) was prognosis for low risk.ConclusionsClustered Neo-Bioscore represents a novel prognostic model of non-pCR carcinoma undergoing NAC with a more simplified and appropriate score pattern in the assessment of prognostic factors.
| S-EPMC6580604 | biostudies-literature
Project description:Biomarkers that can accurately predict treatment response are required for indicating optimal neoadjuvant treatments. The current study assessed the predictive value of secreted protein acidic and rich in cysteine (SPARC) mRNA expression for the response to neoadjuvant nab-paclitaxel (nab-PTX) therapy in patients with breast cancer. It was hypothesized that SPARC expression can affect the response to albumin-bound taxanes, including nab-PTX since SPARC binds albumin with a high affinity. Pre-therapeutic specimens of core needle biopsies were analyzed from 50 patients in a phase II trial of neoadjuvant nab-PTX and the factors that were associated with a pathological complete response (pCR) were assessed. The pre-therapeutic tumor mRNA levels of chemotherapy-related proteins were quantified, including SPARC, and the correlations with post-therapeutic clinicopathological factors were assessed, including with pCR. The results demonstrated that pre-therapeutic SPARC mRNA expression was significantly higher in non-pCR patients compared with patients with pCR (92.37±55.33 vs. 56.53±30.19; P=0.027). A cutoff point of 48.5 was determined using receiver operating characteristic (ROC) curve analysis (sensitivity, 83.3%; specificity, 50.0%), and patients were classified into low and high SPARC expression groups. High SPARC expression was associated with histological grade (P=0.035), estrogen receptor expression (P=0.037), and progesterone receptor expression (P=0.002) but not with HER2 (P=0.895), and Ki-67 LI (P=0.743) expression. The results of the current study indicated that a high SPARC mRNA expression was a negative predictor of pCR following neoadjuvant nab-PTX therapy regardless of breast cancer subtype. The phase II study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of the National Hospital Organization Takasaki General Medical Center (Registration nos. H23-9 and H23-33).
| S-EPMC7068243 | biostudies-literature