scholarly journals A Novel 4-gene Score to Predict Survival, Distant Metastasis and Response to Neoadjuvant Therapy in Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1148 ◽  
Author(s):  
Masanori Oshi ◽  
Eriko Katsuta ◽  
Li Yan ◽  
John M.L. Ebos ◽  
Omar M. Rashid ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Marker Genes ◽  
Gene Score ◽  
Primary Tumors ◽  
Predictive Values ◽  
Free Survival ◽  
Response To Neoadjuvant Chemotherapy

We generated a 4-gene score with genes upregulated in LM2-4, a metastatic variant of MDA-MB-231 (DOK 4, HCCS, PGF, and SHCBP1) that was strongly associated with disease-free survival (DFS) in TCGA cohort (hazard ratio [HR]>1.2, p < 0.02). The 4-gene score correlated with overall survival of TCGA (HR = 1.44, p < 0.001), which was validated with DFS and disease-specific survival of METABRIC cohort. The 4-gene score was able to predict worse survival or clinically aggressive tumors, such as high Nottingham pathological grade and advanced cancer staging. High score was associated with worse survival in the hormonal receptor (HR)-positive/Her2-negative subtype. High score enriched cell proliferation-related gene sets in GSEA. The score was high in primary tumors that originated, in and metastasized to, brain and lung, and it predicted worse progression-free survival for metastatic tumors. Good tumor response to neoadjuvant chemotherapy or hormonal therapy was accompanied by score reduction. High scores were also predictive of response to neoadjuvant chemotherapy for HR-positive/Her2-negative subtype. High score tumors had increased expression of T cell exhaustion marker genes, suggesting that the score may also be a biomarker for immunotherapy response. Our novel 4-gene score with both prognostic and predictive values may, therefore, be clinically useful particularly in HR-positive breast cancer.

4-gene score to predict response to neoadjuvant chemotherapy, metastasis, and survival.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12592-e12592
Author(s):  
Masanori Oshi ◽  
Eriko Katsuta ◽  
Li Yan ◽  
Itaru Endo ◽  
Kazuaki Takabe
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Metastatic Breast ◽  
Breast Cancer Dataset ◽  
Gene Score ◽  
Cancer Dataset ◽  
Predictive Values ◽  
Study Results ◽  
Response To Neoadjuvant Chemotherapy

e12592 Background: At this point, there is no treatment to cure metastatic breast cancer. On the other hand, improvement of treatment of metastatic breast cancer is the key to further improve breast cancer survival. One possible opportunity is to detect metastatic breast cancer in it’s “early” phase when it many respond to treat such as immune therapy. We hypothesized that a scoring system generated from metastatic clone predict metastasis and survival. Methods: A gene signature score was generated using differentially expressed genes between MDA-MB-231 human breast cancer cell-line and its highly metastatic variant, LM2-4, and TCGA breast cancer dataset. METABRIC cohort as well as six neoadjuvant therapeutic cohorts and four metastatic cohorts were used as validation cohort. The totals of 4,199 samples from a large number of cohorts were analyzed in the study. Results: Among the 297 genes that were up-regulated in LM2-4, tumor expression of four genes had the strongest association with disease-free survival in TCGA breast cancer dataset (hazard ratio [HR] > 1.2 with p < 0.02). A 4-gene score calculated from the combined expression of these genes correlated with overall survival in TCGA data, with HR of 1.44 (95% confidence interval [CI] = 1.52-2.98; p < 0.001). The association of higher scores with worse survival was also observed for disease-specific survival in the METABRIC breast cancer cohort (HR = 1.57, 95% CI = 1.23-1.72, p < 0.001). Tumors with high score enriched gene sets related with cancer aggressiveness such as E2F, G2F, MYC v1 and v2 (FDR = 0.23, 0.19, 0.20, 0.21, respectively), whereas those with lower score enriched estrogen response pathway related set (FDR = 0.13) in TCGA and it was validated with METABRIC cohorts. We also found that the score associated with distant metastasis to brain or lung (p < 0.001). Kaplan-Meier analyses of site-specific metastasis-free interval demonstrated that for all three cohorts, patients with high scores had significantly increased risk for development of metastasis to the lung (p≤0.02). This association of the score with metastasis risk was also seen for brain for two cohorts, and it was seen for bone in one cohort. Importantly, we found that the high score group had a higher pCR rate than the low score group for especially ER+/HER2- breast cancer in two cohorts (p = 0.003 and p = 0.004). And the score significantly decreases with good response to neoadjuvant chemotherapy (p = 0.022) or hormonal therapy (p = 0.013). Conclusions: This novel gene score may be clinically useful with both prognostic and predictive values for breast cancer.

scholarly journals Obesity and Response to Neoadjuvant Chemotherapy in Breast Cancer: Implication of The Apelinergic System.

2020 ◽  
Author(s):  
Florian Gourgue ◽  
Françoise Derouane ◽  
Cedric van Marcke ◽  
Elodie Villar ◽  
Helene Dano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Two Factors ◽  
Obese Subjects ◽  
Circulating Levels ◽  
Response To Neoadjuvant Chemotherapy

Abstract Obese subjects present higher risk of developing mammary tumors, worse disease free survival and altered response to neoadjuvant chemotherapy (NAC). The circulating levels of the apelin adipokines are increased in obese subjects and are associated with poorer prognosis in cancer patients. In this study, we showed that obesity and tumoral apelin expression are two factors associated with incomplete response to NAC in breast cancer patients.

scholarly journals Predictive Factors Involved in Determining Response to Neoadjuvant Chemotherapy in Breast Cancer and Impact of Response on 5 Years Disease Free Survival and Overall Survival

2020 ◽  
pp. 1-6
Author(s):  
Bushra Rehman ◽  
Bushra Rehman ◽  
Osama Shakeel ◽  
Sara Rehman ◽  
Naseera Khanum ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Predictive Factors ◽  
Disease Free Survival ◽  
Survival Outcome ◽  
Research Centre ◽  
Free Survival ◽  
Response Group ◽  
Disease Free ◽  
Response To Neoadjuvant Chemotherapy

Objective: To evaluate all the known factors that may play a role in predicting response to Neoadjuvant chemotherapy in breast cancer and to see impact of response on five years’ disease free survival (DFS) and Overallsurvival (OS). Material and Method: Data of 156 patients was reviewed retrospectively from January 2012 to December 2012 at Shaukat Khanum Memorial Cancer Hospital and Research Centre Lahore, Pakistan. All received neoadjuvant chemotherapy (NAC) and had no distant metastasis. The response was measured in term of percentage reduction from 1st radiological size on presentation to final size on histopathology (of resected specimen). Four groups were identified, complete responder (CR) (100% reduction), Responders (R) (>50% reduction), Partial responder (PR) (<50% reduction) and Non-responder (NR). Relationship of predictive factors with each response group was observed. Five year survival was noted for each response group. Result: Median age of patients was 45 years (25-64 years). 67% of patients underwent breast conservation surgery, while the rest underwent mastectomy. Mortality for whole group was 22%, and recurrence was shown in 34% (Majority i.e. 26% were distant, while contralateral were 3%). Out of 156 patients, 25% of patients were CR, 13% were NR, 23% were PR and 37% were R. Progesterone receptor negative and Grade III tumors showed more complete responses. The Rest of the receptor types, including triple negative, initial T and N stage and other clinical factors showed no impact on chemo-response. Survival was significantly poor in NR group (45% OS, 40% DFS), while rest of three groups had comparable survival outcome, with CR group having best survival outcome (86% OS, 80% DFS). Conclusion: Most of factors studied did not show impact on achieving good chemo response, however good chemo response did show better survival.

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.

Mamographic density and disease-free survival in [HR+, HER2-] locally advanced breast cancer treated with neoadjuvant chemotherapy.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. e11536-e11536 ◽  
Author(s):  
Katerin Ingrid Rojas ◽  
Raymundo Flores ◽  
Claudio J Flores ◽  
Joseph A. Pinto ◽  
Henry Leonidas Gomez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Advanced Breast Cancer ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Advanced Breast ◽  
Free Survival ◽  
Disease Free

Association of non-disruptive P53 mutations with poor progression-free survival (PFS) in resected breast cancer treated with neoadjuvant chemotherapy.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 1042-1042
Author(s):  
Alejandro Martinez-Bueno ◽  
Sonia Baulies ◽  
Miguel Angel Molina-Vila ◽  
Jordi Bertran-Alamillo ◽  
Maria Gonzalez Cao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Progression Free Survival ◽  
P53 Mutations ◽  
Free Survival

Meta-analysis of prognostic biomarkers for pancreatic neuroendocrine tumors (PNETs).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15688-e15688
Author(s):  
Mojun Zhu ◽  
Thorvardur Ragnar Halfdanarson ◽  
Bonnie Elyssa Gould Rothberg
Keyword(s):  
Proportional Hazards ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Enzyme Linked Immunosorbent Assay ◽  
Source Population ◽  
Inclusion Criteria ◽  
Primary Tumors ◽  
Free Survival ◽  
Specific Pcr

e15688 Background: PNETs are marked by histological heterogeneity and variable clinical outcomes. Other than Ki67 index, reliable circulating or tissue biomarkers for prognosis do not exist. Methods: PubMed was searched through 01/31/2017. Inclusion criteria were: 1) prospective/retrospective cohort with defined source population, boundary dates, and justifications for exclusions; 2) assay of primary tumors; 3) clear descriptions of methods including techniques and controls; 4) use of multivariate proportional hazards modeling adjusted for prognostic factors including but not limited to stage or grade; and 5) reporting adjusted hazard ratios (HR) with 95 % confidence intervals and P values. Studies with < 50 % PNETs were excluded. PNET-specific data was summarized in the table. Results: A total of 2958 manuscripts were identified and 462 manuscripts were reviewed. Only 23 multivariate studies met all inclusion criteria. These altogether analyzed 24 unique targets and 14 were associated with survival. Conclusions: This meta-analysis identified 14 markers associated with survival of PNET patients. Future studies should adhere to the REMARK criteria and incorporate the 2017 WHO grading system for multivariate analysis. 1. I-immunohistochemistry, F-fluorescence in situ hybridization, E-enzyme linked immunosorbent assay, M- methylation specific PCR, P-polymerase chain reaction; 2. O-overall survival, F-disease free survival, S-disease specific survival, P- progression free survival.[Table: see text]

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