Abnormal Long Non-Coding RNAs Expression Patterns Have the Potential Ability for Predicting Survival and Treatment Response in Breast Cancer

Abnormal long non-coding RNAs (lncRNAs) expression has been documented to have oncogene or tumor suppressor functions in the development and progression of cancer, emerging as promising independent biomarkers for molecular cancer stratification and patients’ prognosis. Examining the relationship between lncRNAs and the survival rates in malignancies creates new scenarios for precision medicine and targeted therapy. Breast cancer (BRCA) is a heterogeneous malignancy. Despite advances in its molecular classification, there are still gaps to explain in its multifaceted presentations and a substantial lack of biomarkers that can better predict patients’ prognosis in response to different therapeutic strategies. Here, we performed a re-analysis of gene expression data generated using cDNA microarrays in a previous study of our group, aiming to identify differentially expressed lncRNAs (DELncRNAs) with a potential predictive value for response to treatment with taxanes in breast cancer patients. Results revealed 157 DELncRNAs (90 up- and 67 down-regulated). We validated these new biomarkers as having prognostic and predictive value for breast cancer using in silico analysis in public databases. Data from TCGA showed that compared to normal tissue, MIAT was up-regulated, while KCNQ1OT1, LOC100270804, and FLJ10038 were down-regulated in breast tumor tissues. KCNQ1OT1, LOC100270804, and FLJ10038 median levels were found to be significantly higher in the luminal subtype. The ROC plotter platform results showed that reduced expression of these three DElncRNAs was associated with breast cancer patients who did not respond to taxane treatment. Kaplan–Meier survival analysis revealed that a lower expression of the selected lncRNAs was significantly associated with worse relapse-free survival (RFS) in breast cancer patients. Further validation of the expression of these DELncRNAs might be helpful to better tailor breast cancer prognosis and treatment.

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Prognostic and predictive value of EGFR and EGFR-ligands in blood of breast cancer patients: a systematic review

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2017-0592 ◽

2018 ◽

Vol 56 (5) ◽

pp. 688-701 ◽

Cited By ~ 17

Author(s):

Ina Mathilde Kjaer ◽

Troels Bechmann ◽

Ivan Brandslund ◽

Jonna Skov Madsen

Keyword(s):

Breast Cancer ◽

Systematic Review ◽

Cancer Patients ◽

Predictive Value ◽

Predictive Biomarkers ◽

Response To Treatment ◽

Current Evidence ◽

Breast Cancer Patients ◽

Baseline Serum ◽

Egfr Ligands

AbstractEpidermal growth factor receptor (EGFR) serves as a co-target for dual/pan-EGFR-inhibitors in breast cancer. Findings suggest that EGFR and EGFR-ligands are involved in resistance towards certain breast cancer treatments. The aim is to explore the validity of EGFR and EGFR-ligands in blood as prognostic and predictive biomarkers in breast cancer. The systematic review was conducted in accordance to the PRISMA guidelines. Literature searches were conducted to identify publications exploring correlations between EGFR/EGFR-ligands in serum/plasma of breast cancer patients and prognostic/predictive outcome measures. Sixteen publications were eligible for inclusion. Twelve studies evaluated EGFR, whereas five studies evaluated one or more of the EGFR-ligands. Current evidence indicates associations between low baseline serum-EGFR and shorter survival or reduced response to treatment in patients with advanced breast cancer, especially in patients with estrogen and/or progesterone receptor positive tumors. The prognostic and predictive value of EGFR and EGFR-ligands in blood has only been investigated in highly selected subsets of breast cancer patients and most studies were small. This is the first systematic review evaluating the utility of EGFR and EGFR-ligands as predictive and prognostic biomarkers in blood in breast cancer. Further exploration in large well-designed studies is needed.

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Serum Long Non-Coding RNAs PVT1, HOTAIR, and NEAT1 as Potential Biomarkers in Egyptian Women with Breast Cancer

Biomolecules ◽

10.3390/biom11020301 ◽

2021 ◽

Vol 11 (2) ◽

pp. 301

Author(s):

Amal Ahmed Abd El-Fattah ◽

Nermin Abdel Hamid Sadik ◽

Olfat Gamil Shaker ◽

Amal Mohamed Kamal ◽

Nancy Nabil Shahin

Keyword(s):

Breast Cancer ◽

Logistic Regression ◽

Cancer Patients ◽

Breast Cancer Diagnosis ◽

Serum Levels ◽

Breast Cancer Patients ◽

Multivariate Logistic Regression ◽

Expression Levels ◽

Non Coding Rnas ◽

Pai 1

Long non-coding RNAs play an important role in tumor growth, angiogenesis, and metastasis in several types of cancer. However, the clinical significance of using lncRNAs as biomarkers for breast cancer diagnosis and prognosis is still poorly investigated. In this study, we analyzed the serum expression levels of lncRNAs PVT1, HOTAIR, NEAT1, and MALAT1, and their associated proteins, PAI-1, and OPN, in breast cancer patients compared to fibroadenoma patients and healthy subjects. Using quantitative real-time PCR (qRT-PCR), we compared the serum expression levels of the four circulating lncRNAs in patients with breast cancer (n = 50), fibroadenoma (n = 25), and healthy controls (n = 25). The serum levels of PAI-1 and OPN were measured using ELISA. Receiveroperating-characteristic (ROC) analysis and multivariate logistic regression were used to evaluate the diagnostic value of the selected parameters. The serum levels of HOTAIR, PAI-1, and OPN were significantly higher in breast cancer patients compared to controls and fibroadenoma patients. The serum level of PVT1 was significantly higher in breast cancer patients than in the controls, while that of NEAT1 was significantly lower in breast cancer patients compared to controls and fibroadenoma patients. Both ROC and multivariate logistic regression analyses revealed that PAI-1 has the greatest power in discriminating breast cancer from the control, whereas HOTAIR, PAI-1, and OPN have the greatest power in discriminating breast cancer from fibroadenoma patients. In conclusion, our data suggest that the serum levels of PVT1, HOTAIR, NEAT1, PAI-1, and OPN could serve as promising diagnostic biomarkers for breast cancer.

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PITX2 DNA-Methylation: Predictive versus Prognostic Value for Anthracycline-Based Chemotherapy in Triple-Negative Breast Cancer Patients

Breast Care ◽

10.1159/000510468 ◽

2020 ◽

pp. 1-9

Author(s):

Rudolf Napieralski ◽

Gabriele Schricker ◽

Gert Auer ◽

Michaela Aubele ◽

Jonathan Perkins ◽

...

Keyword(s):

Breast Cancer ◽

Dna Methylation ◽

Cancer Patients ◽

Triple Negative Breast Cancer ◽

Predictive Value ◽

Untreated Patient ◽

Triple Negative ◽

Statistical Significance ◽

Breast Cancer Patients ◽

The Impact

Background: PITX2 DNA methylation has been shown to predict outcomes in high-risk breast cancer patients after anthracycline-based chemotherapy. To determine its prognostic versus predictive value, the impact of PITX2 DNA methylation on outcomes was studied in an untreated cohort vs. an anthracycline-treated triple-negative breast cancer (TNBC) cohort. Material and Methods: The percent DNA methylation ratio (PMR) of paired-like homeodomain transcription factor 2 (PITX2) was determined by a validated methylation-specific real-time PCR test. Patient samples of routinely collected archived formalin-fixed paraffin-embedded (FFPE) tissue and clinical data from 144 TNBC patients of 2 independent cohorts (i.e., 66 untreated patients and 78 patients treated with anthracycline-based chemotherapy) were analyzed. Results: The risk of 5- and 10-year overall survival (OS) increased continuously with rising PITX2 DNA methylation in the anthracycline-treated population, but it increased only slightly during 10-year follow-up time in the untreated patient population. PITX2 DNA methylation with a PMR cutoff of 2 did not show significance for poor vs. good outcomes (OS) in the untreated patient cohort (HR = 1.55; p = 0.259). In contrast, the PITX2 PMR cutoff of 2 identified patients with poor (PMR >2) vs. good (PMR ≤2) outcomes (OS) with statistical significance in the anthracycline-treated cohort (HR = 3.96; p = 0.011). The results in the subgroup of patients who did receive anthracyclines only (no taxanes) confirmed this finding (HR = 5.71; p = 0.014). Conclusion: In this hypothesis-generating study PITX2 DNA methylation demonstrated predominantly predictive value in anthracycline treatment in TNBC patients. The risk of poor outcome (OS) correlates with increasing PITX2 DNA methylation.

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Predictive value of survivin alternative transcript expression in locally advanced breast cancer patients treated with neoadjuvant chemotherapy

International Journal of Molecular Medicine ◽

10.3892/ijmm_00000129 ◽

1998 ◽

Author(s):

Lizard-Nacol

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Advanced Breast Cancer ◽

Cancer Patients ◽

Predictive Value ◽

Locally Advanced Breast Cancer ◽

Locally Advanced ◽

Alternative Transcript ◽

Transcript Expression ◽

Breast Cancer Patients

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Prognostic and predictive value of TP53mutations in node-positive breast cancer patients treated with anthracycline- or anthracycline/taxane-based adjuvant therapy: results from the BIG 02-98 phase III trial

Breast Cancer Research ◽

10.1186/bcr3179 ◽

2012 ◽

Vol 14 (3) ◽

Cited By ~ 46

Author(s):

Lynnette Fernández-Cuesta ◽

Catherine Oakman ◽

Priscila Falagan-Lotsch ◽

Ke-seay Smoth ◽

Emmanuel Quinaux ◽

...

Keyword(s):

Breast Cancer ◽

Adjuvant Therapy ◽

Cancer Patients ◽

Predictive Value ◽

Phase Iii ◽

Breast Cancer Patients ◽

Phase Iii Trial ◽

Node Positive ◽

Positive Breast Cancer

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Genotoxic and Cytotoxic Damage by Cyclophosphamide and Adriamycin as a Response to Treatment in Breast Cancer Patients: Pilot Study

Journal of Cancer Therapy ◽

10.4236/jct.2015.62018 ◽

2015 ◽

Vol 06 (02) ◽

pp. 163-168 ◽

Cited By ~ 1

Author(s):

Jimena Garibay-Garcia ◽

Fernando Mejia-Sanchez ◽

Eduardo Ramírez-San-Juan ◽

Miriam V. Flores-Merino ◽

Julieta Castillo-Cadena

Keyword(s):

Breast Cancer ◽

Pilot Study ◽

Cancer Patients ◽

Response To Treatment ◽

Breast Cancer Patients

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Comparing practice patterns and outcomes for early-stage hormone receptor-positive and node-positive breast cancer patients with high-intermediate-risk Oncotype Dx scores in the National Cancer Database.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e12520 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e12520-e12520

Author(s):

Keerthi Tamragouri ◽

Ethan M. Ritz ◽

Ruta D. Rao ◽

Cristina O'Donoghue

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Predictive Value ◽

Practice Patterns ◽

Early Stage ◽

Oncotype Dx ◽

Breast Cancer Patients ◽

Node Positive ◽

The Impact ◽

Positive Breast Cancer

e12520 Background: Oncotype Dx (ODX) is a commercial diagnostic test primarily used to predict the likely benefit from chemotherapy in ER+, HER2-, and node negative breast cancer. The prognostic value (recurrence risk) has also been demonstrated to apply to early stage lymph node positive (LN+) disease in a number of retrospective and prospective studies. The ongoing RxPONDER trial aims to clarify the predictive value of RS in LN+ population. In light of the initial results, we analyzed the practice patterns and outcomes for HR+/Her2 -/node positive breast cancer patients receiving ODX testing in the years from 2010-2017 with RS 14-25 in a retrospective observational study of the NCDB. Methods: Women with HR+/Her2 -/node positive breast cancer receiving ODX testing from 2010-2017 were identified in the NCDB using TAILORx and RxPONDER patients’ inclusion criteria: ages 18-75, 6-50mm invasive tumors, N1, M0, ER+/HER2 -. The impact of ODX results in the high-intermediate range (14-25) and other clinico-pathologic variables on the receipt of chemotherapy were compared. Additionally, we examined the impact of chemotherapy on overall survival (OS). Frequencies, Kaplain-Meier analysis, and changepoint analysis using the Contal and O’Quigley method were utilized. Results: There were 109,652 T1-2 and N1 patients of whom 32,506 (29.6%) received ODX testing. 13,461 (41.4%%) women had scores in the high-intermediate (14-25) range. The majority tended to have only 1 LN involved (1LN: 77.2%, 2LNs: 17.5%, 3LNs: 5.3%), had a mean age of 57.8y, were Caucasian (86.4%), and were preferentially tested at academic or comprehensive community cancer programs (79.2%). 6,610 (49.3%) patients were recommended chemotherapy, the median ODX score for all women who were recommended chemotherapy was 20 compared to 17 for those whom chemotherapy was not recommended. 5,068 (76.7%) women had documentation of receiving chemotherapy which correlated with improved OS regardless of age. Conclusions: In the group of women with HR+/Her2 -/node positive breast cancer, clinicians appear to utilize ODX testing in less than one-third of patients, possibly finding RS to be most useful in guiding adjuvant therapy recommendations when only 1LN is involved. Both the recommendation and receipt of chemotherapy correlated linearly with increasing RS, as expected based on the current NCCN guideline recommendations. We identified an OS benefit when chemotherapy was administered, regardless of patient age. Long-term follow-up in the RxPONDER trial will likely continue to clarify the predictive value of RS < 25 in the ER+/HER2-/node positive breast cancer population.

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Predictive and prognostic role of tumour-infiltrating lymphocytes in breast cancer patients with different molecular subtypes: a meta-analysis

BMC Cancer ◽

10.1186/s12885-020-07654-y ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Zhao-hua Gao ◽

Cun-xin Li ◽

Ming Liu ◽

Jia-yuan Jiang

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Cancer Patients ◽

Predictive Value ◽

Molecular Subtypes ◽

Molecular Subtype ◽

Meta Analysis ◽

Breast Cancer Patients ◽

Tumour Infiltrating Lymphocytes ◽

Infiltrating Lymphocytes

Abstract Background Whether tumour-infiltrating lymphocytes (TILs) play different roles in different molecular subtypes of breast cancer remains unknown. Additionally, their prognostic and predictive value in different molecular subtypes of breast cancer is still controversial. The aim of our meta-analysis was to assess the prognostic and predictive value of TILs in different molecular subtypes of breast cancer by summarizing all relevant studies performing multivariate analysis. Methods PubMed, Embase, EBSCO, ScienceDirect, the Cochrane Database and Web of Science were comprehensively searched (until March 2020). Hazard ratios (HRs), odds ratios (ORs) and their 95% confidence intervals (CIs) were used as effect measures to perform our meta-analysis. A random effect model was used. Stata software, version 15 (2017) (StataCorp, College Station, TX, USA) was used to perform the statistical analysis. Results Thirty-three studies including 18,170 eligible breast cancer patients were analysed. The meta-analysis showed that high TIL expression was significantly associated with increased pathological complete response (pCR) rates after neoadjuvant chemotherapy in patients with the HER2-enriched molecular subtype (OR = 1.137, 95% CI [1.061 ~ 1.218], p < 0.001) and triple-negative breast cancer (TNBC) subtype (OR = 1.120, 95% CI [1.061 ~ 1.182], p < 0.001). However, high TIL expression was not significantly associated with high pCR rates after neoadjuvant chemotherapy in patients with the luminal molecular subtype of breast cancer (OR = 1.154, 95% CI [0.789 ~ 1.690], p = 0.460). We carried out a meta-analysis on the HRs of overall survival (OS) and disease-free survival (DFS) to assess the prognostic value of TILs in breast cancer with different molecular subtypes more deeply. Our meta-analysis confirmed that high TILs were associated with significantly improved DFS in patients with the HER2-enriched molecular subtype [HR = 0.940, 95% CI (0.903 ~ 0.979), p = 0.003] and TNBC molecular subtype [HR = 0.907, 95% CI (0.862 ~ 0.954), p < 0.001]. However, high TILs were not associated with significantly better DFS in patients with the luminal molecular subtype of breast cancer [HR = 0.998, 95% CI (0.977 ~ 1.019), p = 0.840]. Furthermore, the results confirmed that high TILs were significantly related to better OS in patients with the HER2-enriched molecular subtype [HR = 0.910, 95% CI (0.866 ~ 0.957), p < 0.001] and TNBC molecular subtype [HR = 0.869, 95% CI (0.836 ~ 0.904), p < 0.001]. Conversely, the summarized results indicated that high TILs were significantly associated with poor OS in patients with the luminal molecular subtype of breast cancer [HR = 1.077, 95% CI (1.016 ~ 1.141), p = 0.012]. Conclusions Our meta-analysis confirms that high TILs are associated with favourable survival and predicts pCR in breast cancer patients with the TNBC and HER2-enriched molecular subtypes.

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Young Age is not an Ominous Prognostic Factor in Breast Cancer Patients

Tumori Journal ◽

10.1177/030089168707300305 ◽

1987 ◽

Vol 73 (3) ◽

pp. 233-235 ◽

Cited By ~ 15

Author(s):

Giuseppe Muscolino ◽

Corrado Villani ◽

Amedeo Vittorio Bedini ◽

Alberto Luini ◽

Bruno Salvadori

Keyword(s):

Breast Cancer ◽

Prognostic Factor ◽

Cancer Patients ◽

Young Women ◽

Survival Rates ◽

Disease Free Survival ◽

Young Age ◽

Breast Cancer Patients ◽

Free Survival ◽

Disease Free

Analysis of a series of 137 women 20–30 years of age, operated for breast carcinoma, excluding patients pregnant, lactating or with inflammatory cancer, showed that disease-free survival rates were similar and not lower than those reported for a large series of 716 breast cancer patients of all ages, treated and followed at the same Institute. Ten-year disease-free survival rates for the two series of 137 young women and 716 patients of all ages were 43.7% and 47.1% respectively. Even when considering the subgroups of patients with and without nodal axillary involvement, the corresponding figures for the two series considered were 72.6% vs. 72.1% (N−) and 25.1% vs. 24.5% (N+). It can be concluded that young age cannot be considered as an unfavorable prognostic factor.

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