Breast cancer subtype discordance: impact on post-recurrence survival and potential treatment options.
Ontology highlight
ABSTRACT:
SUBMITTER: McAnena PF
PROVIDER: S-EPMC5819681 | biostudies-other | 2018 Feb
REPOSITORIES: biostudies-other
Publications
Breast cancer subtype discordance: impact on post-recurrence survival and potential treatment options.
McAnena Peter F PF McGuire Andrew A Ramli A A Curran C C Malone C C McLaughlin R R Barry K K Brown James A L JAL Kerin M J MJ
BMC cancer 20180220 1
<h4>Background</h4>Recent studies have shown that breast cancer subtype can change from the primary tumour to the recurrence. Discordance between primary and recurrent breast cancer has implications for further treatment and ultimately prognosis. The aim of the study was to determine the rate of change between primary and recurrence of breast cancer and to assess the impact of these changes on survival and potential treatment options.<h4>Methods</h4>Patient demographics were collected on those w ...[more]
Similar Datasets
Project description:IntroductionBreast cancer is the most common cancer among women and one of the major causes of mortality and morbidity worldwide. The aim of this study is to determine two-year cumulative recurrence rates and survival rates and their influential factors among women with breast cancer after surgical treatment.MethodsThe breast cancer registry with focus on patient's outcome after treatment was retrospectively review for relevant data. The study was started on 2019. All breast cancer patients who underwent surgical procedure between 2016 and 2019 were identified and recruited in this study and was follow up for two year. We performed Kaplan Meier method to determine 2-year recurrence rates and survival rates and compared unadjusted survival statistics using Log-rank test between baseline variables and outcomes.ResultFrom 2016 to 2019, a total of 482 breast cancer patients underwent surgical procedure. The overall observed 2-year recurrence rate among breast cancer patients after surgical treatment was 11.8% (95%CI:8.5,16.4) while for the survival rate was 94.8% (95% CI:91.8,96.7). Log rank test showed that lymph node involvement (p < 0.001) and high lymph node ratio (p < 0.001) were associated with higher cumulative recurrence rates. Meanwhile, stage 4 breast cancer (p = 0.001), higher grade tumour (p = 0.011), larger tumour size (>5 cm) (P = 0.005) and type of tumour (p = 0.018) were demonstrated to have lower survival rates.ConclusionRecurrence rate were significant predictor among patient with lymph node involvement and higher lymph node ratio, while stages of tumour, tumour grade, size of tumour and type of tumour were all highly significant predictor for survival rate. Therefore, the aim for early diagnosis and management of breast cancer is crucial in improving the treatment outcome.
| S-EPMC9486850 | biostudies-literature
Project description:PurposeTo investigate whether estrogen receptor (ER), progesterone receptor (PR) and Ki-67 expression discordance before and after neoadjuvant chemotherapy (NAC) correlates with prognosis and treatment of breast cancer patients.MethodsThe study cohort included 482 breast cancer patients at the Zhejiang Cancer Hospital from January 1, 2008, to December 31, 2018. Core needle biopsies and excised tissue biopsies pre- and post-NAC were obtained. Immunohistochemistry was used to determine ER, PR and Ki-67 status. The relationship between biomarker discordance before and after NAC and clinicopathological features was compared retrospectively.ResultsER (n = 482), PR (n = 482) and Ki-67 (n = 448) expression was assessed in the same lesion pre- and post-NAC. Discordance in the three markers pre- and post-NAC was observed in 50 (10.4%), 82 (17.0%) and 373 (77.4%) cases, respectively. Positive-to-negative PR expression changes were the most common type of discordance observed. The risk of death in patients with a PR positive-to-negative conversion was 6.58 times greater than for patients with stable PR expression. The risk of death in patients with increased Ki-67 expression following NAC treatment was 2.05 times greater than for patients with stable Ki-67 expression.ConclusionBreast cancer patients showed changes in ER, PR and/or Ki-67 status throughout NAC, and these changes possibly influenced disease-free survival and overall survival. A switch to negative hormone receptor expression with increased Ki-67 expression following NAC could be indicators of a worse prognosis. Biomarker expression investigations following NAC may potentially improve patient management and survival.
| S-EPMC7162523 | biostudies-literature
Project description:PurposeAdiposity has been linked with increased breast cancer risk and mortality. It is established that etiologic associations for adiposity vary by tumor subtype, but the influence of adiposity on subtype-specific survival is unknown.MethodsStudy participants were 1,109 invasive breast cancer participants in the population-based Carolina Breast Cancer Study, diagnosed between 1993 and 2001, and with tissue blocks available for immunohistochemical subtyping. General and central adiposities were assessed by body mass index (BMI) and waist-to-hip ratio (WHR), respectively, based on in-person measurements after diagnosis. Vital status as of 2011 was determined using the National Death Index (median follow-up = 13.5 years). Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer (BC)-specific and all-cause mortalities.ResultsAmong all patients, high WHR (≥0.84), but not BMI, was associated with all-cause mortality (adjusted HR 1.50, 95% CI 1.11-2.05, <0.77 as reference). No significant association between adiposity and BC-specific mortality was detected, although there was a suggestion of increased mortality risk among high-BMI (≥30 kg/m(2)) patients with basal-like tumors (adjusted HR 2.44, 95% CI 0.97-6.12, <25 kg/m(2) as reference). Quantitative differences in all-cause mortality were observed by subtype, with BMI associated with basal-like mortality and WHR associated with luminal mortality. The associations were attenuated by tumor characteristics.ConclusionsOur study confirms the association of adiposity and unfavorable overall survival in breast cancer patients and suggests that this association may vary by intrinsic subtype and adiposity measure.
| S-EPMC5057532 | biostudies-literature
Project description:BackgroundStudies of obesity and survival among patients with breast cancer produce conflicting results, possibly because of heterogeneity by molecular subtype.MethodsThis study examined whether the association of body mass index (BMI) at diagnosis with breast cancer recurrence and survival varied across subtypes defined by PAM50 (Prediction Analysis of Microarray 50) gene expression. Included were 1559 Kaiser Permanente Northern California members ages 18 to 79 years who had PAM50 assays and were diagnosed with American Joint Committee on Cancer stage I through III breast cancer from 1996 to 2013. Patients reported weight and height. Cox regression models were adjusted for age, menopause, race/ethnicity, stage, and chemotherapy.ResultsOver a median of 9 years (maximum, 19 years), 378 women developed recurrent disease, and 312 died from breast cancer. Overall, BMI was not associated with breast cancer recurrence or survival when controlling for subtype (eg, the hazard ratio per 5 kg/m2 of BMI was 1.05 [95% confidence interval, 0.95-1.15] for breast cancer-specific death). However, associations varied by subtype. Among women with luminal A cancers, those who had class II/III obesity, but not class I obesity or overweight, had worse outcomes. When women who had a BMI ≥35 kg/m2 were compared with those who had a BMI from 18.5 to <25 kg/m2 , the hazard ratio was 2.24 (95% confidence interval,1.22-4.11) for breast cancer-specific death and 1.24 (95% confidence interval, 1.00-1.54) for recurrence. There was no association within luminal B, basal-like or human epidermal growth factor over-expressing subtypes.ConclusionsAmong patients who had accurately classified breast cancer subtypes based on gene expression, a BMI ≥35 kg/m2 was adversely associated with outcomes only among those who had luminal A cancers. Research is needed into whether tailoring recommendations for weight management to tumor characteristics will improve outcomes. Cancer 2017;123:2535-42. © 2017 American Cancer Society.
| S-EPMC5474169 | biostudies-literature
Project description:To identify a melanoma microRNA (miRNA) expression signature that is predictive of outcome and then evaluate its potential to improve risk stratification when added to the standard-of-care staging criteria.Total RNA was extracted from 59 formalin-fixed paraffin-embedded melanoma metastases and hybridized to miRNA arrays containing 911 probes. We then correlated miRNA expression with post-recurrence survival and other clinicopathologic criteria.We identified a signature of 18 miRNAs whose overexpression was significantly correlated with longer survival, defined as more than 18 months post-recurrence survival. Subsequent cross-validation showed that a small subset of these miRNAs can predict post-recurrence survival in metastatic melanoma with an estimated accuracy of 80.2% (95% confidence interval, 79.8-80.6%). In contrast to standard-of-care staging criteria, a six-miRNA signature significantly stratified stage III patients into "better" and "worse" prognostic categories, and a multivariate Cox regression analysis revealed the signature to be an independent predictor of survival. Furthermore, we showed that most miRNAs from the signature also showed differential expression between patients with better and worse prognoses in the corresponding paired primary melanoma.MiRNA signatures have potential as clinically relevant biomarkers of prognosis in metastatic melanoma. Our data suggest that molecularly based models of risk assessment can improve the standard staging criteria and support the incorporation of miRNAs into such models.
| S-EPMC4662869 | biostudies-literature
Project description:Epilepsy is a chronic neurologic disorder that affects over 70 million people worldwide. Despite the availability of over 20 antiseizure drugs (ASDs) for symptomatic treatment of epileptic seizures, about one-third of patients with epilepsy have seizures refractory to pharmacotherapy. Patients with such drug-resistant epilepsy (DRE) have increased risks of premature death, injuries, psychosocial dysfunction, and a reduced quality of life, so development of more effective therapies is an urgent clinical need. However, the various types of epilepsy and seizures and the complex temporal patterns of refractoriness complicate the issue. Furthermore, the underlying mechanisms of DRE are not fully understood, though recent work has begun to shape our understanding more clearly. Experimental models of DRE offer opportunities to discover, characterize, and challenge putative mechanisms of drug resistance. Furthermore, such preclinical models are important in developing therapies that may overcome drug resistance. Here, we will review the current understanding of the molecular, genetic, and structural mechanisms of ASD resistance and discuss how to overcome this problem. Encouragingly, better elucidation of the pathophysiological mechanisms underpinning epilepsies and drug resistance by concerted preclinical and clinical efforts have recently enabled a revised approach to the development of more promising therapies, including numerous potential etiology-specific drugs ("precision medicine") for severe pediatric (monogenetic) epilepsies and novel multitargeted ASDs for acquired partial epilepsies, suggesting that the long hoped-for breakthrough in therapy for as-yet ASD-resistant patients is a feasible goal. SIGNIFICANCE STATEMENT: Drug resistance provides a major challenge in epilepsy management. Here, we will review the current understanding of the molecular, genetic, and structural mechanisms of drug resistance in epilepsy and discuss how the problem might be overcome.
| S-EPMC7300324 | biostudies-literature
Project description:Currently, seven molecular subtypes of prostate cancer (PCa) are known, the most common of which being the subtype characterized by the presence of the TMPRSS2-ERG fusion transcript. While there is a considerable amount of work devoted to the influence of this transcript on the prognosis of the disease, data on its role in the progression and prognosis of PCa remain controversial. The present study is devoted to the analysis of the association between the TMPRSS2-ERG transcript and the biochemical recurrence of PCa. The study included two cohorts: the RNA-Seq sample of Russian patients with PCa (n = 72) and the TCGA-PRAD data (n = 203). The results of the analysis of the association between the TMPRSS2-ERG transcript and biochemical recurrence were contradictory. The differential expression analysis (biochemical recurrence cases versus biochemical recurrence-free) and the gene set enrichment analysis revealed a list of genes involved in major cellular pathways. The GNL3, QSOX2, SSPO, and SYS1 genes were selected as predictors of the potential prognostic model (AUC = 1.000 for a cohort of Russian patients with PCa and AUC = 0.779 for a TCGA-PRAD cohort).
| S-EPMC8234735 | biostudies-literature
Project description:ObjectiveTo summarize the risk factors and emphasize the prognostic importance of the site of recurrent neuroendocrine cervical cancer (NECC).MethodsWe enrolled 88 patients who developed recurrence after radical surgery for pathological stage I-IVa primary NECC between January 2003 and 30 December 2020 and classified these cases into 7 groups based on the initial recurrence. The risk factors for post-recurrence survival (PRS) were analyzed by Kaplan-Meier and Cox regression methods.ResultsAmong 88 NECC patients, nearly all patients (95.50%) experienced progression within 3 years. The time to progression was significantly longer in patients with lung recurrence than in patients without lung recurrence (p = 0.008). After the first recurrence, the median follow-up was 11.1 months (range 2.37-65.50 months), and the 5-year PRS was only 20.6%. The depth of invasion in the primary surgery, number of recurrent sites, abdominal organ recurrence were correlated with PRS by univariate analysis. Multivariate analyses revealed that the number of recurrent sites (p = 0.025) and abdominal organ recurrence (p = 0.031) were independent prognostic factors. Notably, the combination of immune checkpoint inhibitors and chemotherapy, with or without surgery, showed a 43.8% objective response rate in recurrent NECC.ConclusionPatients with abdominal organ recurrence need more sophisticated therapy. The combination of immune therapy and chemotherapy might be an opportunity for recurrent NECC.
| S-EPMC9195210 | biostudies-literature
Project description:Maintenance therapy post autologous stem cell transplant (ASCT) is commonly employed in myeloma patients to prolong remission, as relapse invariably occurs after ASCT. After initial diagnosis and risk stratification, patients receive initial therapy with a combination of drugs, typically a proteasome inhibitor and an immunomodulatory imide drug (IMiD), and in those considered eligible, high-dose chemotherapy followed by autologous stem cell transplant. The aim of our study was to review the literature and consolidate evidence regarding different maintenance therapies post stem cell transplant in myeloma patients. We reviewed major databases including PubMed, Cochrane Library and Evidence-Based Medicine Reviews (EBMR), along with American Society of Hematology/American Society of Clinical Oncology (ASH/ASCO) conference abstracts to include relevant literature. Ongoing clinical trials were also reviewed. Consolidation therapy is often employed to enhance the response to induction therapy and SCT and also to delay progression. Melphalan and thalidomide with or without steroids were initially used as maintenance therapy. More recently, lenalidomide-, bortezomib-, ixazomib-, or carfilzomib-based regimens have been employed as maintenance. Lenalidomide and bortezomib are the most commonly used drugs, with the latter being preferred in high-risk populations. Newer trials are utilizing tumor-specific antigen based vaccines along with adoptive T-cell therapies, and monoclonal antibodies as maintenance therapy. We conclude that maintenance therapy post SCT, with lenalidomide or bortezomib is the standard of care in myeloma patients. Patient tolerability, disease risk stratification and prior therapy received are major determinants of the choice of maintenance. Significant toxicity associated with maintenance therapies is a hindrance to long-term maintenance post stem cell transplant.
| S-EPMC8140028 | biostudies-literature
Project description:PurposeOncotype DX, a gene expression assay widely employed to aid decision making on adjuvant chemotherapy use in patients with primary oestrogen receptor-positive (ER+) breast cancer, produces a recurrence score (RS) related to distant disease recurrence (DR) risk (RS%). In node-negative patients, RS can be integrated with clinicopathological parameters to derive RS-pathology-clinical (RSPC) that improves prognostic accuracy.MethodsData were collected on patients having clinically indicated tests with an intermediate clinical risk of distant recurrence, and for whom the decision to prescribe chemotherapy remained unclear. Correlation between RS% and RSPC scores was examined. An agreement table was constructed using risk-categorised data. Association between RS%-derived categorical risk assignments and treatment recommendation was evaluated.ResultsData on 171 tests (168 patients) were available. Median DR risk by RS% was 11% (range 3-34%), by RSPC it was 15% (range 4-63%). Correlation between RS% and RSPC was 0.702 (p < 0.001). RS% classified 57.3% of cases as low-, 32.2% intermediate- and 10.5% high-risk for DR; by RSPC proportions were 33.9, 35.7, and 30.4%, respectively. The number of patients receiving chemotherapy recommendations was: 14/87 (16.1%) categorised as low-risk by RS%, 27/49 (55.1%) as intermediate-risk and 12/13 (92.3%) as high-risk. Of 149 patients recommended for endocrine treatment alone, 28 (18.8%) were categorised by RS% as low-risk but by RSPC as intermediate- or high-risk.ConclusionsIn this group of patients, RSPC assessed fewer patients as low-risk and more as high-risk than did RS%. The discordances between the scores indicate that RSPC estimates of risk should be considered when selecting patients for endocrine therapy alone.
| S-EPMC5847032 | biostudies-literature