Nomogram to Predict Subsequent Brain Metastasis in Patients With Metastatic Breast Cancer

2010 ◽  
Vol 28 (12) ◽  
pp. 2032-2037 ◽  
Author(s):  
Olivier Graesslin ◽  
Bassam S. Abdulkarim ◽  
Charles Coutant ◽  
Florence Huguet ◽  
Zsolt Gabos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastasis ◽  
Multivariate Logistic Regression Analysis ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Prognostic Features ◽  
Stage Iv Breast Cancer ◽  
Significant Difference ◽  
Selection Of

PurposeBrain metastasis is usually a fatal event in patients with stage IV breast cancer. We hypothesized that its occurrence can be predicted if a clinical nomogram can be developed, thus allowing for selection of enriched patient populations for prevention trials.Patients and MethodsElectronic medical records of patients with metastatic breast cancer were retrospectively reviewed for the period between January 2000 and February 2007 under a study approved by the institutional review board. A multivariate logistic regression analysis of selected prognostic features was done. A nomogram to predict brain metastasis was constructed and validated in a cohort of 128 patients with brain metastasis treated at the Cross Cancer Institute (Edmonton, Alberta, Canada).ResultsOf 2,136 patients with breast cancer, 362 developed subsequent brain metastasis. Age, grade, negative status of estrogen receptor and human epidermal growth factor receptor 2, number of metastatic sites (one v > one), and short disease-free survival were significantly and independently associated with subsequent brain metastasis. The nomogram showed an area under the receiver operating characteristic curve (AUC) of 0.68 (95% CI, 0.66 to 0.69) in the training set. The validation set showed a good discrimination with an AUC of 0.74 (95% CI, 0.70 to 0.79). The nomogram was well calibrated, with no significant difference between the predicted and the observed probabilities.ConclusionWe have developed a robust tool that is able to predict subsequent brain metastasis in patients with breast cancer with nonbrain metastatic disease. Selection of an enriched patient population at high risk for brain metastasis will facilitate the design of trials aiming at its prevention.

scholarly journals O28: M6A DEMETHYLASE FTO A POTENTIAL TARGET IN BRAIN METASTATIC BREAST CANCER

2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
S Keelan ◽  
S Charmsaz ◽  
S Purcell ◽  
D Varešlija ◽  
S Cocchiglia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastasis ◽  
Disease Progression ◽  
Therapeutic Target ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Potential Therapeutic Target ◽  
Rna Methylation ◽  
Pharmacological Inhibition

Abstract Introduction Brain metastasis (BrM) occurs in 10-30% of patients with advanced breast cancer (BC). BrM is increasing in incidence and confers a poor prognosis. We aimed to investigate the contribution of global epi-transcriptomic alterations in N6-methyladenosine (m6A) RNA-methylation as a therapeutic target in brain metastatic breast cancer. Method In preliminary studies we have demonstrated m6A demethylase – FTO as the main contributor to the progression of ER+ breast cancer. Furthermore an association between FTO and reduced disease-free-survival (n=870, p=0.018) was observed. Here we conducted an epigenetic inhibitor screen using two therapeutic agents, ethyl-ester-meclofenamic acid (MA2) and FB23-2 on matched 2D cell line, 3D organoid cultures and patient-derived xenografts (PDX) explant models of brain metastasis. Result Upon integration of mapped global RNA methylation landscape with matched proteomic analysis, we observed genome-wide RNA hypo-methylation of key pluripotency genes, including SOX2 and KLF4, as key players underlying tumour progression to the brain.  Genetic and pharmacological inhibition of FTO in novel ex vivo models of BrM significantly reduced protein expression levels of KLF4 and SOX2. Moreover, pharmacological inhibition of FTO with MA2 and FB23-2, inhibited cell proliferation in endocrine-resistant BC and patient BrM cells. We translate our findings to the clinic by demonstrating the efficacy of anti-FTO therapies in several unique PDX and 3D organoid BrM models. Conclusion Our results reveal epi-transcriptional remodelling events as a key mechanism in BrM. This study establishes an early role for targeting RNA methylation in the management of disease progression and presents FTO as a potential therapeutic target in BrM. Take-home message This study establishes an early role for targeting RNA methylation in the management of disease progression and presents FTO as a potential therapeutic target in brain metastatic breast cancer.

Observational cross-sectional study to evaluate the prognostic factors influencing the selection of bevacizumab combined with chemotherapy in patients with HER2-negative metastatic breast cancer in routine clinical practice. ONCOSUR-AVALOX study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11074-e11074
Author(s):  
Luis Manso ◽  
Ramon Perez-Carrion ◽  
Jose Ignacio Chacon Lopez-Muniz ◽  
Andres Garcia Palomo ◽  
Elena Galve Calvo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Clinical Benefit ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Complete Response ◽  
First Line ◽  
Cross Sectional ◽  
Metastatic Site ◽  
Selection Of

e11074 Background: Combining bevacizumab (BEV) with chemotherapy (CT) improves survival in HER2-negative metastatic breast cancer (MBC). We investigated the influence of age, ECOG, hormonal status, number of sites and location of metastases and patient decision on the selection of BEV combined with CT in MBC. Methods: Observational cross-sectional multicenter study in pts with HER2-negative MBC who have received first-line CT with BEV. Results: From November 2010 to November 2011, 124 pts were included: median age 51 (45-64) yr; ECOG: 0=50%; 60% pre-menopausic; 23% triple-negative (TN); 77% hormone receptor-positive (HR+). Metastatic disease: ≥3 sites=42% (TN: 32%; HR+: 45%); location: 44% bone, 35% lung, 30% liver. Most frequent BEV-based combinations were paclitaxel/BEV (53%) and docetaxel/BEV (14.5%); median no. of CT cycles: 6 (5-8). A disease-free survival (DFS) ≥12 months was achieved by 73%; TN: 68%; HR+: 76%. Overall response rate (ORR) was 58%: 51% partial response (PR), 7% complete response (CR); 28% stable disease (SD) and 10% disease progression. TN: ORR 44% (40% PR), clinical benefit 80% (36% SD); HR+: ORR 62% (54% PR), clinical benefit 87% (25% SD). 58% presented at least one toxicity, mainly grade 1-2; 26% BEV-related: only 3 (2.4%) grade 3 toxicities; no grade 4. Receiving adjuvant hormonal therapy was associated to DFS ≥12 months (p<0.05). ER+ tumors (OR: 0.215; 95% CI: 0.08-0.56; p=0.002) and one metastatic site, vs. ≥3 sites (OR: 0.309; 95% CI: 0.12-0.83; p=0,020) were independent factors associated with the selection of paclitaxel-BEV therapy in the overall population (TN or HR+). Metastases in the liver were significantly related to paclitaxel-BEV administration (p<0.01). Conclusions: Our findings suggest that first-line CT with BEV is an active and tolerable treatment option for pts with TN and HR+ MBC. ER+ tumors and a single metastatic site were identified as independent factors for the selection of a paclitaxel-BEV therapy. The presence of metastases in the liver was significantly associated to the administration of a paclitaxel-BEV regimen.

Prognostic factors influencing the selection of bevacizumab combined with chemotherapy in patients with HER2-negative metastatic breast cancer in routine clinical practice: Oncosur-Avalox—Observational cross-sectional study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e12020-e12020
Author(s):  
Luis Manso ◽  
Andres Garcia-Palomo ◽  
Ramon Perez-Carrion ◽  
Jose Ignacio Chacon ◽  
Xabier Mielgo Rubio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Liver Metastases ◽  
Clinical Benefit ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
First Line ◽  
Cross Sectional ◽  
Patient Decision ◽  
Selection Of

e12020 Background: Combining bevacizumab (BEV) with chemotherapy (CT) improves survival in HER2-negative metastatic breast cancer (MBC). We investigated the influence of age, ECOG, hormonal status, number of sites, location of metastases and patient decision on the selection of BEV combined with CT in MBC. Methods: Observational cross-sectional multicenter study in patients with HER2- negative MBC who have received first-line CT with BEV. Results: 219 patients were included: median age 51(44-63) yr; ECOG: 0=53%; 60.4% pre-menopausic; 23.9% triple-negative (TN);76.2 % hormone receptor positive (HR+).Metastatic disease: ≥3 sites=39.2% (TN: 22%; HR+: 43.9%); location: 45.2% bone, 37.4% liver, 30.1% lung. Most frequent BEV combinations were paclitaxel/BEV(60.7%) and docetaxel/BEV(12.8%); median no. of CT cycles: 6 (5- 8). A disease-free survival (DFS) ≥12 months was achieved by 82.8%; TN: 78.9%; HR+: 83.3%. Overall response rate (ORR) was 62.7%: 53.6% partial response (PR), 9.1% complete response (CR); 25.4% stable disease (SD) and 7.2% disease progression (4.8% non evaluated). TN:ORR 54.2% (47.9% PR), clinical benefit 80% (27.1% SD); HR+:ORR 65.8% (55.7% PR), clinical benefit 89.9% (24.1% SD). 66.2% presented at least one toxicity, mainly grade 1-2; 32% BEV-related: only 3 grade 3 toxicities; no grade 4. Receiving adjuvant hormonal therapy was associated to DFS ≥12 months (p<0.05). ER+ tumors (OR:0.326;95%CI:0.16-0.65;p=0.002) and patient decision after consider doctor opinion (OR:0.026;95%CI:0.01-0.74; p=0.085) were independent factors associated with the selection of paclitaxel-BEV in the overall population (TN or HR+). Liver metastases were significantly related to paclitaxel-BEV administration (p<0.01). Conclusions: First-line CT with BEV is an effective and safe scheme for patients with TN and HR+ MBC. ER+ tumors and patient decision after consider doctor opinion were identified as independent factors for the selection of paclitaxel-BEV therapy. The presence of liver metastases was significantly associated to the administration of a paclitaxel-BEV regimen.

scholarly journals The gastrin releasing peptide, GRP, is differentially expressed in brain metastatic breast cancer.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastasis ◽  
Microarray Data ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Primary Tumors ◽  
Gastrin Releasing Peptide ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes to discover genes associated with brain metastasis in patients with metastatic breast cancer. We found that the gastrin releasing peptide, encoded by GRP, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Molecular functions of gastrin releasing peptide may be relevant to the processes by which tumor cells of the breast metastasize to the breast. Down-regulation of GRP may be an important event for metastasis of primary tumor-derived cancer cells to the brain in humans with metastatic breast cancer.

Is It The Time That We Can Depend on Bioscore as a New Staging System in Non-Metastatic Breast Cancer to Predict the Disease-Free Survival?

2021 ◽  
Author(s):  
Rehab Farouk Mohamed ◽  
Donia Hussein Abd El Hameed ◽  
Mohamed Alaa Eldeen Hassan
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Prognostic Value ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Free Survival ◽  
Disease Free

Abstract Purpose: Novel molecular characterization of breast cancer with cellular markers has allowed a new classification that offers prognostic value. This study investigates the prognostic value of the Bioscore among non-metastatic breast cancer patients with respect to disease free survival (DFS).Methods: This study included 317 patients with non-metastatic surgically treated breast cancer; they were identified in the period from January 2015 to December 2018 at Clinical Oncology Department of Assiut University Hospital. Many variables were used; pathologic stage (PS), T stage (T), nodal stage (N), grade (G), estrogen receptor (ER), progesterone receptors (PR), and human epidermal growth factor receptor (HER2) status. Univariate & two multivariate analyses were performed to identify which of these variables are associated with disease-free survival (DFS). Results: The only significant factors in the Univariate analysis were PS3, T2, T3, T4, N3, G2, G3, ER -ve, PR -ve, and HER2 –ve. The factors which were significant in the first multivariate analysis; PS3, G3, ER –ve, and in the second one were; T2, T4, N3, G3, and ER –ve. Two sets of models were built to determine the utility of combining variables. Models incorporating G and E status had the highest C-index (0.72) for T+N + G + ER in comparison with (0.69) for (PS+ G + ER) and the lowest AIC (953.01) for T + N + G + E and (966.9) for PS + G + E. Conclusions: This study confirms the prognostic significance of bioscore in non-metastatic breast cancer in concerning DFS.

Sign in / Sign up

Export Citation Format

Share Document