Real-world treatment patterns and outcomes in HER2 positive MBC patients with brain metastasis in the U.S. community oncology setting.

2016 ◽  
Vol 34 (7_suppl) ◽  
pp. 92-92 ◽  
Author(s):  
Debra A. Patt ◽  
Eileen Fonseca ◽  
Bongin Yoo ◽  
Thomas Wilson ◽  
Hans-Peter Goertz ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Performance Status ◽  
Metastatic Breast ◽  
Her2 Positive ◽  
Primary Tumors ◽  
Whole Brain Radiation ◽  
Community Oncology ◽  
Estrogen Receptor Positive ◽  
And Performance ◽  
Metastatic Sites

92 Background: Patients (pts) with HER2 positive (HER2+) metastatic breast cancer (MBC) have different patterns of disease and treatment (tx) from HER2 negative MBC. Brain metastasis (BM) frequently occurs and txs vary. Methods: This retrospective study included adult HER2+ MBC pts from a community oncology network electronic health record (EHR) database and diagnosed between 2009-2011, with follow-up until 11/2014. Pts with other primary tumors were excluded. Two cohorts were defined: pts diagnosed with BM and pts with no evidence of BM (NBM), and were initially matched on age and performance status at MBC diagnosis (dx) and stage. Eligibility and txs were examined in electronic chart review. Overall survival (OS) from MBC dx was estimated using a weighted Kaplan-Meier method. Results: The final sample consisted of 86 BM and 101 NBM pts. All baseline MBC demographics were similar across cohorts. Median age was 54 and 52 years for BM and NBM, respectively. The cohorts (BM:NBM) included 57%:75% Caucasians, 12%:6% Blacks, and 31%:19% other/unknown. There were fewer estrogen receptor positive pts in the BM cohort (58%:74%; p = 0.02). Except for bone (p = 0.01), both cohorts had similar prevalence of metastatic sites: liver 35%:35%; lung 31%:30%; bone 41%:62. Of all the BM pts, 54% had first CNS imaging after symptoms, 37% were first imaged for other known reasons. After BM dx, 20% had surgical resection, 67% whole brain radiation (XRT), 37% stereotactic XRT, and 22% palliative XRT (not mutually exclusive). 25% of pts had both XRT and surgery while 72% had only XRT. Among pts receiving systemic therapy after BM dx, the first regimen contained trastuzumab in 55% of pts and lapatinib in 41% of pts. Among pts changing txs after BM dx, 1/3 switched to a trastuzumab but not lapatinib-based regimen; 1/3 to a lapatinib but not trastuzumab-based regimen; 17% to a lapatinib + trastuzumab-based regimen; and 17% to non-HER2-based therapy. Weighted median OS from MBC dx for BM vs. NBM pts was 30.2 and 46.1 months (p = 0.01). Conclusions: For HER2+ MBC pts, survival was shorter for pts with BM vs. NBM and a high degree of tx variability for BM existed. Understanding how detection and tx impacts outcomes will improve care of BM pts.

Randomized Phase II Trial of First-Line Trastuzumab Plus Docetaxel and Capecitabine Compared With Trastuzumab Plus Docetaxel inHER2-Positive Metastatic Breast Cancer

2010 ◽  
Vol 28 (6) ◽  
pp. 976-983 ◽  
Author(s):  
Andrew M. Wardley ◽  
Xavier Pivot ◽  
Flavia Morales-Vasquez ◽  
Luis M. Zetina ◽  
Maria de Fátima Dias Gaui ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Performance Status ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
First Line ◽  
Her2 Positive ◽  
Grade 3

PurposeTo evaluate trastuzumab (H) and docetaxel (T) with or without capecitabine (X) as first-line combination therapy for human epidermal growth factor receptor 2 (HER2) -positive advanced breast cancer.Patients and MethodsPatients with HER2-positive locally advanced or metastatic breast cancer were randomly assigned to H (8 mg/kg loading; 6 mg/kg every 3 weeks) plus T (75 mg/m2in HTX arm, 100 mg/m2in HT arm, every 3 weeks) with or without X (950 mg/m2twice per day on days 1 to 14 every 3 weeks). The primary end point was overall response rate (ORR).ResultsIn 222 patients, median follow-up was approximately 24 months. ORR was high with both regimens (70.5% with HTX; 72.7% with HT; P = .717); complete response rate was 23.2% with HTX compared with 16.4% with HT. HTX demonstrated significantly longer progression-free survival: median 17.9 months compared with 12.8 months with HT (hazard ratio, 0.72; P = .045), which translates to a gain of around 5 months. Two-year survival probability was 75% with HTX compared with 66% with HT. Febrile neutropenia (27% v 15%) and grade 3/4 neutropenia (77% v 54%) incidences were higher with HT than HTX. Treatment-related grade 3 hand-foot syndrome (17% v < 1%) and grade 3/4 diarrhea (11% v 4%) occurred more commonly with HTX than HT. One case of congestive heart failure occurred in each arm.ConclusionHTX is an effective and feasible first-line therapy for HER2-positive locally advanced or metastatic breast cancer, although it should be reserved for patients with good performance status who are not receiving long-term steroids.

scholarly journals Practice-Changing Interventions in the Systemic Management of Breast Cancer

2020 ◽  
Vol 18 (7.5) ◽  
pp. 941-944
Author(s):  
William J. Gradishar
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Breast Cancer Subtype ◽  
Metastatic Breast ◽  
Parp Inhibitors ◽  
Targeted Agents ◽  
Her2 Positive ◽  
Nccn Guidelines ◽  
Estrogen Receptor Positive ◽  
Treatment Paradigm

Systemic treatment for metastatic breast cancer now incorporates many targeted agents and a plethora of combinations specific to the breast cancer subtype. New to the treatment paradigm are fam-trastuzumab deruxtecan-nxki, and tucatinib for HER2-positive disease; the PI3K inhibitor alpelisib in combination with fulvestrant for estrogen receptor–positive and PIK3CA-mutated tumors; PARP inhibitors for patients with germline BRCA1/2 mutations; and the anti–PD-L1 agent atezolizumab in combination with albumin-bound paclitaxel for triple-negative disease with PD-L1 mutations in tumors. In addition, for estrogen receptor–positive disease, the role of CDK4/6 inhibitors increased substantially during the past year, as overall survival results have emerged. These targeted agents are greatly improving patient outcomes, and thus have all been incorporated into the NCCN Guidelines for Breast Cancer.

scholarly journals A novel 20-gene prognostic score in pancreatic adenocarcinoma

2019 ◽  
Author(s):  
Secil Demirkol Canli ◽  
Ege Dedeoglu ◽  
Muhammad Waqas Akbar ◽  
Baris Kucukkaraduman ◽  
Murat Isbilen ◽  
...  
Keyword(s):  
Immune Cell ◽  
Prognostic Score ◽  
Performance Status ◽  
Cyclin B1 ◽  
Pancreatic Tissue ◽  
Tnm Staging ◽  
Prognostic Indicators ◽  
Ductal Adenocarcinoma ◽  
Primary Tumors ◽  
And Performance

Abstract Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers. Known risk factors for this disease are currently insufficient in predicting mortality. The only FDA approved prognostic biomarker for PDAC patients is CA19-9. This, along with AJCC TNM staging and performance status, are considered important prognostic indicators in clinical practice. In order to better prognosticate patients with PDAC, we identified a novel panel of genes by utilizing publically available microarray and RNAseq data of PDAC tumors from GEO and TCGA. Expression of 20 genes were significantly associated with overall survival in four datasets and event-free survival in TCGA. A score generated based on the expression matrix of these genes could be validated in two independent cohorts. We find that this “Pancreatic cancer prognostic score 20 – PPS20” is dramatically elevated in metastatic tissue compared to primary tumor, and is higher in primary tumors compared to normal pancreatic tissue. Transcriptomic analyses show that tumors with low PPS20 have overall more immune cell infiltration and a higher CD8 T cell/Treg ratio when compared to those with high PPS20. Analyses of proteomic data from TCGA PAAD indicated higher levels of Cyclin B1, RAD51, EGFR and a lower E-cadherin/Fibronectin ratio in tumors with high PPS20. The PPS20 score defines not only prognostic and biological sub-groups but can predict response to targeted therapy options as well. Overall, PPS20 is a stronger and more robust transcriptomic signature when compared to similar, previously published gene lists.

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.

scholarly journals FGFR aberrations increase the risk of brain metastases and predict poor prognosis in metastatic breast cancer patients

2020 ◽  
Vol 12 ◽  
pp. 175883592091530
Author(s):  
Ning Xie ◽  
Can Tian ◽  
Hui Wu ◽  
Xiaohong Yang ◽  
Liping liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastasis ◽  
Poor Prognosis ◽  
Significant Risk ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Genetic Aberrations ◽  
Increased Risk

Background: The survival status of patients with breast cancer and brain metastasis (BCBM) receiving current treatments is poor. Method: We designed a real-world study to investigate using patients’ clinical and genetic aberrations to forecast the prognoses of BCBM patients. We recruited 146 BCBM patients and analyzed their clinical features to evaluate the overall survival (OS). For genetic testing, 30 BCBM and 165 non-brain-metastatic (BM) metastatic breast cancer (MBC) patients from Hunan Cancer Hospital, and 86 BCBM and 1416 non-BM MBC patients from the Geneplus database who received circulating tumor DNA testing, were compared and analyzed. Results: Ki67 >14% and >3 metastatic brain tumors were significant risk factors associated with poor OS, while chemotherapy and brain radiotherapy were beneficial factors for better OS. Compared with non-BM MBC patients, BCBM patients had more fibroblast growth factor receptor ( FGFR) aberrations. The combination of FGFR, TP53 and FLT1 aberrations plus immunohistochemistry HER2-positive were associated with an increased risk of brain metastasis (AUC = 77.13%). FGFR aberration alone was not only a predictive factor (AUC = 67.90%), but also a significant risk factor for poor progression-free survival (Logrank p = 0.029). FGFR1 aberration was more frequent than other FGFR family genes in BCBM patients, and FGFR1 aberration was significantly higher in BCBM patients than non-BM MBC patients. Most FGFR1-amplified MBC patients progressed within 3 months of the late-line (>2 lines) treatment. Conclusion: A group of genetic events, including FGFR, TP53 and FLT1 genetic aberrations, and HER2-positivity, forecasted the occurrence of BM in breast cancers. FGFR genetic aberration alone predicted poor prognosis.

HSR19-111: Disparities in Guideline-Concordant Care Among HER2 Positive Metastatic Breast Cancer Patients

2019 ◽  
Vol 17 (3.5) ◽  
pp. HSR19-111
Author(s):  
Ami M. Vyas ◽  
Hilary Aroke ◽  
Stephen J. Kogut
Keyword(s):  
Cancer Diagnosis ◽  
Performance Status ◽  
Decomposition Analysis ◽  
Metastatic Breast ◽  
Study Cohort ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Related Factors ◽  
Initial Care ◽  
Non Linear

Background: We examined guideline-concordant care among women with HER2+ MBC and determined the magnitude of differences in guideline-concordant care between those with positive and negative hormone receptor (HR) status by utilizing a non-linear decomposition technique. Methods: We conducted a retrospective observational cohort study using the Surveillance, Epidemiology, End Results-Medicare linked database. The study cohort consisted of women age >66 years diagnosed with HER2+ MBC in 2010–2013 (N=241). Guideline-concordant initial care within 6 months of cancer diagnosis was defined as per NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). A multivariate logistic regression was performed to identify the significant predictors of guideline-concordant care. A post-regression non-linear decomposition was conducted to examine the magnitude of disparities in guideline concordant care by women’s HR status. Results: 76.8% of the study cohort received guideline-concordant care, while 23.2% did not. As compared to those who did not receive guideline-concordant care, women who received guideline-concordant care were significantly more likely to have positive HR status (adjusted odds ratio (AOR)=2.11; P=.04), had good performance status (AOR=3.46; P=.0008), and had a higher number of oncology visits (AOR=8.05; P<.0001). With 1 year increase in age at cancer diagnosis, there was 5% lesser likelihood of receiving guideline-concordant care (AOR=0.95; P=.04). From the decomposition analysis, 19.0% of the disparity in guideline-concordant care between women with positive and negative HR status was explained by differences in their characteristics. Enabling characteristics (marital status, census-level income, and education) explained the highest (22.8%) proportion of the disparity, followed by external environmental factors (location of residence, SEER region, hospitals offering oncology services) at 5.3%, and need-related factors (tumor grade, comorbidity, performance status, number of metastases) at 3.2%. Conclusion: Almost one quarter of the study cohort did not receive guideline-concordant care. There are opportunities to improve cancer care for women with negative HR status who have lower socioeconomic status. The high unexplained portion of differences in guideline-concordant care (81.0%) can be due to patient preferences for treatment, propensity to seek care, and organizational and physician-level factors not captured in the database.

Mutations of HER2 gene in HER2-positive metastatic breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13118-13118 ◽  
Author(s):  
T. Prempree ◽  
C. Wongpaksa
Keyword(s):  
Breast Cancer ◽  
Gene Mutations ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Trastuzumab Resistance ◽  
Her2 Gene ◽  
Her2 Positive ◽  
Primary Tumors ◽  
Trastuzumab Therapy ◽  
One Year

13118 Background: HER2 status of Breast Cancer has been assessed by IHC and FISH and used for therapeutic decision with a high degree of success. However, there were numbers of HER2-positive MBC who finally failed the Trastuzumab treatment after initial good response. Mechanisms of intrinsic and acquired Trastuzumab resistance are not yet known. Our Objective is to identify factor or factors responsible for Trastuzumab resistance. Methods: DNA extraction and Sequencing of HER2 gene were performed on primary tumors of HER2-positive 14 MBC patients undergoing Trastuzumab therapy. Re-biopsy were done on new metstatic sites of those cases discovered to have Trastuzumab resistance. Results: Of 14 MBC cases whose tumors showing positive IHC and FISH, there were no mutation found in their HER2 gene, exons 18,19, 20 and 21. However, 3 of 14 cases of MBC undergoing continuous Trastuzumab therapy with excellent response for more than one year, developed the resistance. All three cases had new metstatic sites biopsied, and showed D880N and E837Y mutations in the exon 21 of their HER2 genes. All three cases showed no response to trastuzumab therapy. Conclusions: 1) HER2-positive MBC tumors did not have any HER2 gene mutations in them. 2) Mutations arised in their HER2 gene, exon 21 may be responsible for the intrinsic and acquired Trastuzumab resistance. Additional work in this area is needed to further substantiate our findings. No significant financial relationships to disclose.

Trastuzumab-resistant HER2-positive metastatic breast cancer: Comparing results of lapatinib and capecitabine in brain and other metastatic sites.

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. e11505-e11505
Author(s):  
E. J. Cortes ◽  
M. Bomfim ◽  
B. V. Freitas ◽  
F. Muller ◽  
E. R. Silva ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Her2 Positive ◽  
Metastatic Sites
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