NUSAP1 and KIAA0101 downregulation by neo-adjuvant therapy is associated with better outcome and survival in breast cancer.

2020 ◽  
Author(s):  
Gerardo I. Magallanes-Garza ◽  
Sandra K. Santuario-Facio ◽  
Arlina F. Varela-Varela ◽  
Servando Cardona-Huerta ◽  
Pablo Ruiz-Flores ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Expression Profiles ◽  
Pathological Response ◽  
Primary Tumors ◽  
Before And After ◽  
Neo Adjuvant Chemotherapy

Abstract Background: Studies of molecular changes occurring before and after neo-adjuvant chemotherapy (NCT) for breast cancer may unveil genetic biomarkers to predict therapy response. This study aimed at identifying genomic changes in breast primary tumors of patients under NCT. Gene expression changes were correlated with pathological response and survival.Methods: Gene expression profiles in tissue samples from pre and post NCT were obtained by a non-supervised classification analysis. Thirty-nine patients were classified according to their response to the chemotherapy as pathologic complete responders or non-responders (pCR and no-pCR, respectively). Overall survival was assessed by comparing gene expression values before NCT using the Log-rank (Mantel-Cox) test. Results: A signature constituted by 43 genes was obtained to stratify pCR and no-pCR patients after NCT (FC = + 3, FDR p -value < 0.0298). These genes were involved in regulation of the mitotic nuclear division and the anaphase-promoting complex-dependent catabolic process. Remarkably, over-expression of NUSAP1 and KIAA0101 were associated to poor overall survival. Conclusions: A new expression signature evaluating response for the neo-adjuvant chemotherapy stratified pathological response. The expression levels of NUSAP1 and KIAA0101 before and after the neo-adjuvant therapy may be useful to predict overall survival.

The prospective MammaPrint MINT (Multi-Institutional Neo-adjuvant Therapy) study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS11122-TPS11122
Author(s):  
Charles E. Cox ◽  
Peter William Blumencranz ◽  
Ruben A. Saez ◽  
Robert Wesolowski ◽  
Lisette Stork ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Adjuvant Chemotherapy ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Locally Advanced ◽  
Specific Gene ◽  
Axillary Lymph ◽  
Long Term Outcome ◽  
Neo Adjuvant Chemotherapy

TPS11122 Background: Patients with locally advanced breast cancer (LABC) are often treated with neo-adjuvant chemotherapy to reduce the size of the tumor before definitive surgery. Complete pathologic Response (pCR) predicts better long term outcome. Genomics assays that measure specific gene expression patterns in a patient's primary tumor have become important prognostic and predictive tools for early breast cancer. This study is designed to test the ability of molecular profiling, as well as traditional pathologic and clinical prognostic factors to predict responsiveness to neo-adjuvant chemotherapy in patients with LABC. Methods: Women ≥ 18 yrs with histologically-proven invasive breast cancer T2(≥3.5cm)-T4,N0M0 or T2-T4N1M0, with measurable disease, adequate bone marrow reserves and normal renal and hepatic function who signed informed consent are enrolled. Axillary lymph nodes will be staged according to protocol. MammaPrint risk profile, BluePrint molecular subtyping profile, TargetPrint ER, PR and HER2 single gene readout, and the 56-gene TheraPrint Research Gene Panel will be analysed using the whole genome expression array. Patients will receive neo-adjuvant chemotherapy treatment according to protocol. Response will be measured by centrally assessed Residual Cancer Burden (RCB). Objectives are: (1) To determine the predictive power of MammaPrint and BluePrint for sensitivity to neo-adjuvant chemotherapy as measured by pCR. (2) To identify and/or validate predictive gene expression profiles of clinical response or resistance to neo-adjuvant chemotherapy. (3) To compare TargetPrint ER, PR and HER2 with local and centralized IHC and/or CISH/FISH assessment. (4) To identify correlations between TheraPrint and response to neo-adjuvant chemotherapy. (5) To compare BluePrint molecular subtype with IHC-based subtype classification. To achieve a difference of 20% in chemotherapy sensitivity for patients stratified by MammaPrint, a total of 226 samples is needed (significance level 0.05 and power of 0.90). So far 45 patients have been enrolled from multiple institutions. Clinical trial information: NCT01501487.

scholarly journals DNAJC28 expression associates with survival in triple negative breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Overall Survival ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Microarray Data ◽  
Triple Negative ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Significant Gene

We mined published microarray data (1) to understand the most significant gene expression differences in the tumors of triple negative breast cancer patients based on survival following treatment: dead or alive. We observed significant transcriptome-wide differential expression of DnaJ (Hsp40) homolog, subfamily C, member 28, encoded by DNAJC28 when comparing the primary tumors of triple negative breast cancer patients dead or alive. Importantly, DNAJC28 expression was correlated with overall survival in patients with breast cancer. DNAJC28 may be of relevance as a biomarker or as a molecule of interest in understanding the etiology or progression of triple negative breast cancer.

Taxanes-based neoadjuvant chemotherapy in advanced nonmetastatic breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e12033-e12033
Author(s):  
Tahir Mehmood ◽  
Muhammad Ali ◽  
Kamran Saeed ◽  
Atif Munawar ◽  
Sadaf Usman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Neoadjuvant Chemotherapy ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Pathological Response ◽  
Free Survival ◽  
Neo Adjuvant Chemotherapy ◽  
Disease Free

e12033 Background: Pakistan has the highest rate of breast cancer for any South Asian population and majority of the patients present with locally advanced or metastatic disease. We report on response and survival of primary locally advanced non-metastatic breast cancer in women treated with neoadjuvant Adriamycin/Taxanes (AT) based regimens at our institute. Methods: Between 1995 to 2009 the hospital information system identified 517 women with pathologically confirmed locally advanced breast cancer. All patients received neoadjuvant chemotherapy with AT based regimen followed by surgery. Median age was 43 years (range 17-71 years). AJCC stage; stage II 54% and stage III 46% of the patients. Axillary nodes were palpable in 72% of the patients at presentation. Histological sub-types; infiltrating ductal carcinoma 95%, infiltrating lobular carcinoma 3% and others 2% respectively. Pathological grade was I/II in 44% and grade III 56% of the patients. ER, PR, and Her2-neu receptors were positive in 44%, 40% and 24% of the patients respectively. Twenty one percent of the patients had triple negative breast cancer. Post operative radiotherapy was delivered to 94% of the patients. Patients with positive ER/PR receptors also received hormonal manipulation. Results: Following neo-adjuvant chemotherapy, pathological response was; complete response (CR) 13.5%, partial response 21%, stable disease 52% and progressive disease in 13% of the patients respectively. Breast conservation was possible in 36% of the patients. The 5 year disease free survival in patients with and without CR was 81% and 36% respectively. On multivariate analysis, T stage (p = 0.001) and response to neo-adjuvant chemotherapy (p = 0.001) were found to be independent predictors for disease free survival. Conclusions: Pathological response to neoadjuvant chemotherapy is a predictor of long term survival. Chemotherapy regimens with high response rates merit evaluation in randomized trials to improve outcome in locally advanced breast cancer.

Assessment of efficacy of trastuzumab (Herceptin) comprising adjuvant therapy of HER2+ breast cancer patients determined based upon statistical analysis of overall survival (OS) and disease-free survival (PFS)

2018 ◽  
Vol 6 (1) ◽  
Author(s):  
Beata Jagielska ◽  
Andrzej Czubek ◽  
Konrad Tałasiewicz ◽  
A. Twarowski ◽  
P. Rutkowski ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Statistical Analysis ◽  
Adjuvant Therapy ◽  
Disease Free Survival ◽  
Clinical Staging ◽  
Primary Tumors ◽  
Free Survival ◽  
Adjuvant Immunotherapy ◽  
Disease Free

Introduction In patients suffering from breast cancer, adjuvant radiation, chemotherapy, or immunotherapy, which immediately follow the surgery as the first line therapy, greatly improve overall (OS) and disease-free survival (DFS). Various regimens of adjuvant therapy for these patients have been tested contingent upon the clinical staging. Inclusion of adjuvant immunotherapy is particularly promising. Specific aim The aim of this study was to assess efficacy of trastuzumab (Herceptin) - comprising adjuvant immunotherapy in terms of overall and disease-free survival as compared to other adjuvant therapies. Patients All patients were presented with the Patient Bill of Rights and have provided the Patient Informed Consent to participate in this study. Eligible patients include those with primary tumors initially staged at the clinical stages: I-T1c N0, II-T0-2, N0-1, or IIIA-T3 N1, or patients for whom neoadjuvant chemotherapy provides the possibility to remove surgically a tumor at the stage IIIA T0-3 N2. Of 9,058 patients enrolled in the Breast Cancer Treatment Program between 2008 and 2015, 6,832 fulfilled the inclusion criteria. Statistical Analysis The effects of clinical and demographic factors on overall survival (OS) and disease-free survival (DFS) were assessed using Cox’s proportional hazards regression models. OS and DFS were evaluated with Kaplan-Meier calculations. The study was meeting the criteria for a controlled, open-access clinical trial. Results OS rates for years 1-7 were, respectively, 99.42%, 97.26%, 94.57%, 92.41%, 90.48%, 88.63%, and 88.23%; thus with the 5-year survival at 90.48%. The corresponding data for DFS were 96.17%, 84.07%, 77.26%, 72.57%, 68.59%, 65.04%, and 63.05%, respectively; thus with the 5-year DFS at 68.59%. Adverse effects, with the exception of cardiac complications, occurred in 1194 (17%), while causing withdrawal of 421 (6%) patients. Most of other adverse events were related to hepatotoxicity 1755 (25%) and fatigue 681 (9.7%). Conclusion These results demonstrate the great benefits of inclusion of immunotherapy as the adjuvant component as currently the best overall therapeutic strategy for the patients suffering breast cancers. As this strategy greatly exceeds any other therapeutic options available for practicing oncologists at the present time, it definitely justifies allocation of all needed public resources, while assuring highest quality health service for the patients in Poland.

Gene expression profiles of circulating tumor cells versus primary tumors in metastatic breast cancer

2015 ◽  
Vol 362 (1) ◽  
pp. 36-44 ◽  
Author(s):  
Wendy Onstenk ◽  
Anieta M. Sieuwerts ◽  
Marleen Weekhout ◽  
Bianca Mostert ◽  
Esther A. Reijm ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Metastatic Breast ◽  
Primary Tumors

Is Axillary Lymph Node Dissection Indicated for Early-Stage Breast Cancer? A Decision Analysis

1999 ◽  
Vol 17 (5) ◽  
pp. 1465-1465 ◽  
Author(s):  
Giovanni Parmigiani ◽  
Donald A. Berry ◽  
Eric P. Winer ◽  
Claudia Tebaldi ◽  
J. Dirk Iglehart ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Axillary Lymph Node Dissection ◽  
Lymph Node Dissection ◽  
Axillary Lymph Node ◽  
Axillary Lymph ◽  
Node Dissection ◽  
Primary Tumors

PURPOSE: Axillary lymph node dissection (ALND) has been a standard procedure in the management of breast cancer. In a patient with a clinically negative axilla, ALND is performed primarily for staging purposes, to guide adjuvant treatment. Recently, the routine use of ALND has been questioned because the results of the procedure may not change the choice of adjuvant systemic therapy and/or the survival benefit of a change in adjuvant therapy would be small. We constructed a decision model to quantify the benefits of ALND for patients eligible for breast-conserving therapy. METHODS: Patients were grouped by age, tumor size, and estrogen receptor (ER) status. The model uses the Oxford overviews and three combined Cancer and Leukemia Group B studies. We assumed that patients who did not undergo ALND received axillary radiation therapy and that the two procedures are equally effective. All chemotherapy combinations were assumed to be equally efficacious. RESULTS: The largest benefits from ALND are seen in ER-positive women with small primary tumors who might not be candidates for adjuvant chemotherapy if their lymph nodes test negative. Virtually no benefit results in ER-negative women, almost all of whom would receive adjuvant chemotherapy. When adjusted for quality of life (QOL), ALND may have an overall negative impact. In general, the benefits of ALND increase with the expected severity of adjuvant therapy on QOL. CONCLUSION: Our model quantifies the benefits of ALND and assists decision making by patients and physicians. The results suggest that the routine use of ALND in breast cancer patients should be reassessed and may not be necessary in many patients.

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