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Effect of Clinical and Treatment Factors on Survival Outcomes of Triple Negative Breast Cancer Patients.

ABSTRACT: Purpose:Triple negative breast cancer (TNBC) accounts for approximately 15% of breast cancer cases and is associated with a poor prognosis. In this retrospective study of patients undergoing radiation therapy as part of their treatment, disease-free survival (DFS) and overall survival (OS) of TNBC patients were examined in relation to clinical and treatment-related factors. Patients and Methods:The electronic records of 214 consecutive TNBC patients treated with surgery followed by radiotherapy at the Mid North Coast Cancer Institute between 2006 and 2016 were reviewed. Overall survival and DFS times were analyzed using the Kaplan-Meier method; multivariate Cox proportional hazard regression modelling was used to assess the significance of prognostic factors. Results:The majority of tumors were T1 (51.9%), followed by T2 (39.2%) and T3 (6.1%). For the whole group, mean DFS was 106.4 (SD 48.7) months; OS 109.4 (SD 52.1) months. Radiotherapy technique, fractionation protocol and laterality were not significant factors for DFS or OS (p>0.05). However, compared to breast conservation, mastectomy was associated with poorer DFS (mean 114.2 vs 65.2 months; p<0.0001) and poorer OS (mean 115.5 vs 80.5 months; p=0.0015). The mastectomy group had fewer patients with tumor size T1 (p=0.001) and higher proportions of T3 (p=0.001) and T4 (p=0.02). On multivariate analysis, tumor size T3/T4 and nodal status N2/N3 were significant factors for reduced DFS (p=0.023 and p=0.0003 respectively). Tumor size T3/T4 was the only significant prognostic factor for reduced OS (p=0.019). Conclusion:Advanced disease exhibited by tumor size > 5cm and positive nodal status is associated with poorer DFS in TNBC patients. Radiotherapy technique or fractionation protocol were not associated with differences in DFS or OS in our patient cohort.

SUBMITTER: Wen S

PROVIDER: S-EPMC7064282 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Effect of Clinical and Treatment Factors on Survival Outcomes of Triple Negative Breast Cancer Patients.

Wen Shelly S Manuel Lucy L Doolan Moira M Westhuyzen Justin J Shakespeare Thomas P TP Aherne Noel J NJ

Breast cancer (Dove Medical Press) 20200306

<h4>Purpose</h4>Triple negative breast cancer (TNBC) accounts for approximately 15% of breast cancer cases and is associated with a poor prognosis. In this retrospective study of patients undergoing radiation therapy as part of their treatment, disease-free survival (DFS) and overall survival (OS) of TNBC patients were examined in relation to clinical and treatment-related factors.<h4>Patients and methods</h4>The electronic records of 214 consecutive TNBC patients treated with surgery followed b ...[more]

PMID: 32184654

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Project description:BackgroundTo provide further information on the clinical and pathological prognostic factors in triple-negative breast cancer (TNBC), for which limited and inconsistent data are available.MethodsPathological characteristics and clinical records of 841 TNBCs diagnosed between 1994 and 2015 in four major oncologic centers from Sardinia, Italy, were reviewed. Multivariate hazard ratios (HRs) for mortality and recurrence according to various clinicopathological factors were estimated using Cox proportional hazards models.ResultsAfter a mean follow-up of 4.3 years, 275 (33.3%) TNBC patients had a progression of the disease and 170 (20.2%) died. After allowance for study center, age at diagnosis, and various clinicopathological factors, all components of the TNM staging system were identified as significant independent prognostic factors for TNBC mortality. The HRs were 3.13, 9.65, and 29.0, for stage II, III and IV, respectively, vs stage I. Necrosis and Ki-67 > 16% were also associated with increased mortality (HR: 1.61 and 1.99, respectively). Patients with tumor histotypes other than ductal invasive/lobular carcinomas had a more favorable prognosis (HR: 0.40 vs ductal invasive carcinoma). No significant associations with mortality were found for histologic grade, tumor infiltrating lymphocytes, and lymphovascular invasion. Among lymph node positive TNBCs, lymph node ratio appeared to be a stronger predictor of mortality than pathological lymph nodes stage (HR: 0.80 for pN3 vs pN1, and 3.05 for >0.65 vs <0.21 lymph node ratio), respectively. Consistent results were observed for cancer recurrence, except for Ki-67 and necrosis that were not found to be significant predictors for recurrence.ConclusionsThis uniquely large study of TNBC patients provides further evidence that, besides tumor stage at diagnosis, lymph node ratio among lymph node positive tumors is an additional relevant predictor of survival and tumor recurrence, while Ki-67 seems to be predictive of mortality, but not of recurrence.

Project description:ImportanceTriple-negative breast cancers are known collectively to demonstrate a more aggressive clinical course and earlier recurrence than cancers of other histological subtypes. However, the literature on rare triple-negative breast cancers and the association of histological type with survival and risk of metastasis is sparse.ObjectiveTo present the clinical and demographic characteristics, treatment patterns, and overall survival (OS) for histologically rare (<10% of breast cancers) triple-negative breast cancer types: medullary carcinoma, adenoid cystic carcinoma, and metaplastic breast carcinoma.Design, setting, and participantsThis cohort study was performed in the US using data reported by the National Cancer Database between 2010 and 2016. Confirmed cases of medullary carcinoma, adenoid cystic carcinoma, and metaplastic breast cancer were analyzed. Univariable analyses and multivariable Cox regression models were performed. Data analysis was performed from April to May 2020.Main outcomes and measuresThe primary outcome was 5-year OS. Secondary outcomes included site of metastasis, effect of immunohistochemistry, management, and 2-year mortality.ResultsA total of 8479 patients with breast cancer (mean [SD] age; 62.6 [14.3] years; 8435 women [99.48%]) were analyzed. Metaplastic carcinoma was the most commonly diagnosed histological type in this cohort, with 6867 patients (81%), followed by 1357 (16%) with adenoid cystic carcinoma and only 255 (3%) with medullary carcinoma. Medullary carcinoma presented earlier in life, at a median (interquartile range) age of 53 (45-62) years, compared with 62 (53-72) years for patients with adenoid cystic carcinoma and 63 (52-74) years for patients with metaplastic carcinoma. The proportion of tumors with triple-negative immunohistochemistry varied by histological type for medullary carcinoma (57 patients [22.4%]), adenoid cystic carcinoma (653 patients [48.1%]), and metaplastic carcinoma (3637 patients [53.0%]). Patients with adenoid cystic carcinoma were less likely to receive radiotherapy (711 patients [52.4%]) and chemotherapy (175 patients [12.9%]) compared with patients with medullary carcinoma (radiotherapy, 156 patients [61.2%]; chemotherapy, 190 patients [74.5%]) and metaplastic carcinoma (radiotherapy, 3416 patients [49.7%]; chemotherapy, 4709 patients [68.6%]). The 5-year OS rate was superior for patients with medullary (91.7%) and adenoid cystic carcinoma (88.4%) compared with patients with metaplastic carcinoma (63.1%). The 5-year mortality rate for adenoid cystic carcinoma was 8.33% vs 36.91% for metaplastic carcinoma.Conclusions and relevanceNationally, over the course of 7 years, medullary carcinoma was most common and metaplastic carcinoma had the worst 5-year OS among the rare histological breast cancer subtypes analyzed. Factors associated with a poor prognosis for metaplastic carcinoma included advanced stage, lung metastasis, older age, and not receiving chemotherapy or radiation therapy. Future research focusing on rare subtypes of breast cancer is desirable and could inform the optimal management of these relatively understudied carcinomas.

Project description:ObjectiveTriple-negative breast cancer (TNBC) is aggressive cancer usually diagnosed in young women with no effective prognosis prediction model to use. The present study was performed to develop a useful prognostic model for predicting overall survival (OS) for TNBC patients.MethodsThe Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases were used as training and validation data sets, respectively, in which the gene expression levels and clinical prognostic information of TNBC were collected. Differentially expressed genes (DEGs) between TNBC and non-TNBC (NTNBC) were identified with the thresholds of false discovery rate < 0.05 and |log2 Fold Change| > 1. DEGs in AmiGO2 and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were retained for further study. Univariate, multivariate Cox, and logistic regression analysis were conducted for detecting DEG signature with the threshold of log-rank P < 0.05. The prognosis models of mRNA signature, clinical factors were constructed and compared.ResultsOne five-DEG signature, including CHST4, COCH, CST9, SOX11, and TDGF1 was identified in DEG prognosis model. Stratified analysis showed that the patients aged over 60, with higher pathologic stage (III-IV) and recurrence induced a significantly lower survival rate than those aged below 60, lower pathologic stage and without recurrence. Compared with patients with low-risk scores, those presented high-risk scores demonstrated significantly lower survival rate in the subgroup aged over 60 [HR = 3.780 (1.801-7.933), P < 0.0001]. For patients who obtained a higher pathologic stage and recurrence, high-risk scores were correlated with a significantly lower survival rate than patients with low-risk scores. The five-mRNA signature combined with clinical model (AUC = 0.950) predicted better than single clinical model (AUC = 0.795) or five-mRNA signature model (AUC = 0.823).ConclusionOur present study identified a prognostic prediction model (combined with five-mRNA signature and clinical factors) for TNBC patients receiving immunotherapy, which will benefit future research and clinical therapies.

Project description:ImportanceAgents targeting programmed death ligand 1 (PD-L1) have demonstrated efficacy in triple-negative breast cancer (TNBC) when combined with chemotherapy and are now the standard of care in patients with PD-L1-positive metastatic disease. In contrast to microtubule-targeting agents, the effect of combining platinum compounds with programmed cell death 1 (PD-1)/PD-L1 immunotherapy has not been extensively determined.ObjectiveTo evaluate the efficacy of atezolizumab with carboplatin in patients with metastatic TNBC.Design, setting, and participantsThis phase 2 randomized clinical trial was conducted in 6 centers from August 2017 to June 2021.InterventionsPatients with metastatic TNBC were randomized to receive carboplatin area under the curve (AUC) 6 alone or with atezolizumab, 1200 mg, every 3 weeks until disease progression or unacceptable toxic effects with a 3-year duration of follow-up.Main outcome and measuresThe primary end point was investigator-assessed progression-free survival (PFS). Secondary end points included overall response rate (ORR), clinical benefit rate (CBR), and overall survival (OS). Other objectives included correlation of response with tumor PD-L1 levels, tumor-infiltrating lymphocytes (TILs), tumor DNA- and RNA-sequenced biomarkers, TNBC subtyping, and multiplex analyses of immune markers.ResultsAll 106 patients with metastatic TNBC who were enrolled were female with a mean (range) age of 55 (27-79) years, of which 12 (19%) identified as African American/Black, 1 (1%) as Asian, 73 (69%) as White, and 11 (10%) as unknown. Patients were randomized and received either carboplatin (n = 50) or carboplatin and atezolizumab (n = 56). The combination improved PFS (hazard ratio [HR], 0.66; 95% CI, 0.44-1.01; P = .05) from a median of 2.2 to 4.1 months, increased ORR from 8.0% (95% CI, 3.2%-18.8%) to 30.4% (95% CI, 19.9%-43.3%), increased CBR at 6 months from 18.0% (95% CI, 9.8%-30.1%) to 37.5% (95% CI, 26.0%-50.6%), and improved OS (HR, 0.60; 95% CI, 0.37-0.96; P = .03) from a median of 8.6 to 12.6 months. Subgroup analysis showed PD-L1-positive tumors did not benefit more from adding atezolizumab (HR, 0.62; 95% CI, 0.23-1.65; P = .35). Patients with high TILs (HR, 0.12; 95% CI, 0.30-0.50), high mutation burden (HR, 0.50; 95% CI, 0.23-1.06), and prior chemotherapy (HR, 0.59; 95% CI, 0.36-0.95) received greater benefit on the combination. Patients with obesity and patients with more than 125 mg/dL on-treatment blood glucose levels were associated with better PFS (HR, 0.35; 95% CI, 0.10-1.80) on the combination. TNBC subtypes benefited from adding atezolizumab, except the luminal androgen receptor subtype.Conclusions and relevanceIn this randomized clinical trial, the addition of atezolizumab to carboplatin significantly improved survival of patients with metastatic TNBC regardless of PD-L1 status. Further, lower risk of disease progression was associated with increased TILs, higher mutation burden, obesity, and uncontrolled blood glucose levels.Trial registrationClinicalTrials.gov Identifier: NCT03206203.

Project description:Circulating tumor DNA (ctDNA) in peripheral blood has been used to predict prognosis and therapeutic response for triple-negative breast cancer (TNBC) patients. However, previous approaches typically use large comprehensive panels of genes commonly mutated across all breast cancers. Given the reduction in sequencing costs and decreased turnaround times associated with panel generation, the objective of this study was to assess the use of custom micro-panels for tracking disease and predicting clinical outcomes for patients with TNBC. Paired tumor-normal samples from patients with TNBC were obtained at diagnosis (T0) and whole exome sequencing (WES) was performed to identify somatic variants associated with individual tumors. Custom micro-panels of 4-6 variants were created for each individual enrolled in the study. Peripheral blood was obtained at baseline, during Cycle 1 Day 3, at time of surgery, and in 3-6 month intervals after surgery to assess variant allele fraction (VAF) at different timepoints during disease course. The VAF was compared to clinical outcomes to evaluate the ability of custom micro-panels to predict pathological response, disease-free intervals, and patient relapse. A cohort of 50 individuals were evaluated for up to 48 months post-diagnosis of TNBC. In total, there were 33 patients who did not achieve pathological complete response (pCR) and seven patients developed clinical relapse. For all patients who developed clinical relapse and had peripheral blood obtained ≤ 6 months prior to relapse (n = 4), the custom ctDNA micro-panels identified molecular relapse at an average of 4.3 months prior to clinical relapse. The custom ctDNA panel results were moderately associated with pCR such that during disease monitoring, only 11% of patients with pCR had a molecular relapse, whereas 47% of patients without pCR had a molecular relapse (Chi-Square; p-value = 0.10). In this study, we show that a custom micro-panel of 4-6 markers can be effectively used to predict outcomes and monitor remission for patients with TNBC. These custom micro-panels show high sensitivity for detecting molecular relapse in advance of clinical relapse. The use of these panels could improve patient outcomes through early detection of relapse with preemptive intervention prior to symptom onset.

Dataset Information

Effect of Clinical and Treatment Factors on Survival Outcomes of Triple Negative Breast Cancer Patients.

Publications

Effect of Clinical and Treatment Factors on Survival Outcomes of Triple Negative Breast Cancer Patients.

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