Clinical significance of brain metastases occurrence in HER2 overexpressing metastatic breast cancer patients treated with trastuzumab

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10593-10593
Author(s):  
V. Mari ◽  
E. Chamorey ◽  
A. Italiano ◽  
F. Van Den Bos ◽  
R. Ferri-Dessens ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Metastatic Breast ◽  
Study Cohort ◽  
Breast Cancer Patients ◽  
Specific Patient ◽  
Study Results ◽  
Significant Difference

10593 Background: Recent data report that HER2 overexpressing metastatic breast cancer patients (HER+ MBC pts) treated with trastuzumab (T) have a high rate of Brain metastasis (BM). This study aimed to evaluate the prognostic significance of BM occurrence and the related clinical outcome in a specific patient population. Methods: All the HER+MBC patients treated with trastuzumab (with or without chemotherapy) between 09/1999 and 12/2004 were included in this study. Results: A total of forty three patients were enrolled into the study cohort. The median follow-up was 48 months (range, 11–166). Fifteen patients (35%) developped BM. The median interval from the the first MBC event to BM was 18 months (range, 1–65). In multivariate analysis; younger age was the only factor associated with BM occurrence (46 versus 57 years; p = 0.01). Patients with BM tend to have a longer median duration of response to T than patients without BM (16 months versus 13 months; p = 0.1). At the time of BM appearance, 6 of the 15 patients (40%) were still responding or had achieved extracranial stable disease while receiving trastuzumab. Twelve out of 15 (80%) pts received a whole-brain radiation therapy, and 8 pts continued to receive trastuzumab until extracranial disease progression. The median overall survival for patients diagnosed with BM was 10 months (range, 2–42). At three-year, there was no significant difference in overall survival rates between the two groups. The 3-YS was 63.5% and 66.7% for pts with or without BM, respectively; (p = 0.7). Conclusions: The BM occurrence in HER2+ MBC pts treated with Trastuzumab is not linked to tumour resistance, but likely related to the T inability to cross the blood-brain barrier. There is no impaired survival for these pts treated with effective and appropriate therapy. [Table: see text]

scholarly journals Breast Subtypes and Prognosis of Breast Cancer Patients With Initial Bone Metastasis: A Population-Based Study

2020 ◽  
Vol 10 ◽  
Author(s):  
Deyue Liu ◽  
Jiayi Wu ◽  
Caijin Lin ◽  
Lisa Andriani ◽  
Shuning Ding ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Metastatic Breast Cancer ◽  
Bone Metastasis ◽  
Cancer Patients ◽  
Metastatic Breast ◽  
Risk Groups ◽  
Population Based ◽  
Breast Cancer Patients

BackgroundMetastatic breast cancer (MBC) is a highly heterogeneous disease and bone is one of the most common metastatic sites. This retrospective study was conducted to investigate the clinical features, prognostic factors and benefits of surgery of breast cancer patients with initial bone metastases.MethodsFrom 2010 to 2015, 6,860 breast cancer patients diagnosed with initial bone metastasis were analyzed from Surveillance, Epidemiology, and End Results (SEER) database. Univariate and Multivariable analysis were used to identify prognostic factors. A nomogram was performed based on the factors selected from cox regression result. Survival curves were plotted according to different subtypes, metastatic burdens and risk groups differentiated by nomogram.ResultsHormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2) positive patients showed the best outcome compared to other subtypes. Patients of younger age (<60 years old), white race, lower grade, lower T stage (<=T2), not combining visceral metastasis tended to have better outcome. About 37% (2,249) patients received surgery of primary tumor. Patients of all subtypes could benefit from surgery. Patients of bone-only metastases (BOM), bone and liver metastases, bone and lung metastases also showed superior survival time if surgery was performed. However, patients of bone and brain metastasis could not benefit from surgery (p = 0.05). The C-index of nomogram was 0.66. Cutoff values of nomogram point were identified as 87 and 157 points, which divided all patients into low-, intermediate- and high-risk groups. Patients of all groups showed better overall survival when receiving surgery.ConclusionOur study has provided population-based prognostic analysis in patients with initial bone metastatic breast cancer and constructed a predicting nomogram with good accuracy. The finding of potential benefit of surgery to overall survival will cast some lights on the treatment tactics of this group of patients.

Efficacy and Safety of Capecitabine Alone or in Combination in Advanced Metastatic Breast Cancer Patients Previously Treated with Anthracycline and Taxane: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 43 (12) ◽  
pp. 694-702
Author(s):  
Louai Alsaloumi ◽  
Shaima Shawagfeh ◽  
Abdikarim Abdi ◽  
Bilgen Basgut
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Adverse Events ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Metastatic Breast ◽  
Efficacy And Safety ◽  
Breast Cancer Patients ◽  
Significant Difference ◽  
Hand Foot Syndrome

<b><i>Background:</i></b> Capecitabine is frequently used alone or combined with other chemotherapy agents for the treatment of metastatic breast cancer in relapsed patients. <b><i>Objective:</i></b> The objective of this meta-analysis is to evaluate the effectiveness and safety of capecitabine monotherapy versus combination in the treatment of metastatic breast cancer patients pretreated with anthracycline and taxane. <b><i>Methods:</i></b> Eligible randomized controlled trials examining the efficacy and safety of capecitabine alone compared to capecitabine combination were systematically searched. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and grades 3–4 drug-related adverse events were the outcomes assessed. <b><i>Results:</i></b> A total of 6,714 patients of 9 trials were involved in the pooled analysis. Our findings demonstrated that capecitabine combination is significantly superior to capecitabine monotherapy in improving PFS (hazard ratio [HR] 1.32, 95% CI 1.13–1.54, <i>p</i> &#x3c; 0.0001) and ORR (risk ratio [RR] 0.67, 95% CI 0.54–0.83, <i>p</i> &#x3c; 0.001), but it was insignificant in OS (HR 1.09, 95% CI 0.98–1.22, <i>p</i> = 0.12). On the other hand, the incidence of non-hematological adverse events such as hand-foot syndrome and diarrhea was lower in capecitabine combination compared to capecitabine monotherapy. <b><i>Conclusion:</i></b> Capecitabine-based combination chemotherapy showed superiority over capecitabine monotherapy in terms of PFS and ORR, with no significant difference in OS. Non-hematological adverse effects such as hand-foot syndrome were fewer with a combination regimen. However, hematological adverse events were fewer with capecitabine monotherapy regimen.

Use of pretreatment serum CA9 (carbonic anhydrase 9) to predict PFS and survival in trastuzumab-treated metastatic breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11092-11092
Author(s):  
K. Leitzel ◽  
H. Y. Hou ◽  
V. Shrivastava ◽  
U. Anyanwu ◽  
S. M. Ali ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
First Line ◽  
Her2 Positive ◽  
Pretreatment Serum

11092 Background: Approximately half of HER2-positive breast cancer patients will respond to first-line trastuzumab-containing therapy. However, in those patients with an initial trastuzumab response, most will progress within a year with acquired resistance. Since trastuzumab treatment is also now used in the HER2-positive adjuvant breast cancer setting, trastuzumab resistance will continue to be a vexing clinical problem, and better predictive and prognostic biomarkers are urgently needed. Methods: Serum HER2, tissue inhibitor of metalloproteinase-1 (TIMP-1), urokinase-type plasminogen activator (uPA), CA9, VEGF-165, and endoglin were measured using ELISA assays in 66 metastatic breast cancer patients before starting first-line trastuzumab-containing therapy. The HER2, TIMP-1, uPA, CA9, and VEGF-165 ELISAs were from Oncogene Science/Siemens Healthcare Diagnostics, Cambridge, MA; and the endoglin ELISA was from R&D Systems, Minneapolis, MN. Progression-free (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox modeling with continuous pretreatment serum biomarker variables. Results: Pretreatment serum HER2 (p= 0.005), TIMP-1 (p< 0.0001), uPA (p= 0.006), endoglin (p= 0.008), and CA9 (p <0.0001) were all significant as univariate continuous biomarkers for predicting PFS to first-line trastuzumab-containing therapy, but VEGF was not. In multivariate analysis for PFS with all six biomarkers, only serum CA9 (p= 0.002) was a significant independent covariate. For OS, pretreatment serum HER2 (p= 0.018), TIMP-1 (p< 0.0001), uPA (p< 0.0001), endoglin (p= 0.002), and CA9 (p< 0.0001) were all significant as univariate continuous biomarkers for prognosis, but serum VEGF was not. In multivariate analysis for OS with all six biomarkers, only serum CA9 was a significant independent prognostic covariate (p= 0.001). Conclusions: Elevated pretreatment serum CA9 (a marker of hypoxia) predicts reduced progression-free survival and overall survival in metastatic breast cancer patients treated with first-line trastuzumab-containing therapy. These serum biomarkers deserve further study in larger trials of HER2-targeted breast cancer treatment. Supported by a grant from Komen for the Cure. [Table: see text]

Improvement in survival of breast cancer patients with synchronous metastases

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1063-1063
Author(s):  
A. Y. Salmon ◽  
B. Uziely ◽  
A. Meirowitz ◽  
N. Sharon ◽  
T. Peretz
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Median Survival ◽  
Metastatic Breast ◽  
Tumor Characteristics ◽  
Breast Cancer Patients ◽  
Improvement In Survival ◽  
New Generation

1063 Background: Less than 10% of breast cancer patients are diagnosed with metastatic disease upon initial diagnosis. Once metastases are detected, median survival ranges between 18 and 24 months. Many new chemotherapy agents, hormonal therapy, monoclonal antibodies and supportive care options were presented during the last decade. Although a few randomized trials have demonstrated improvement in survival for various agents, it has not been clear whether the overall survival of these patients has improved. In this study, we analyzed the survival of patients diagnosed with metastatic breast cancer in during the 1990’s Methods: We have analyzed 874 patients diagnosed with breast cancer at our Institute in the years 1991–1994 and 1102 patients in 1996–1999. Tumor characteristics, treatments, and the outcomes of these patients were compared. We used Kaplan-Meier, Wilcoxon test and Cox proportional hazard in order to investigate variants between the 2 groups. Results: After excluding all women with no evidence of metastatic disease at diagnosis, we analyzed 96 patients. No major difference in tumor characteristics was found between the group of patients diagnosed in the early 1990’s and the group diagnosed in the late 1990’s. We found a significant relationship between the period of diagnosis of metastatic breast cancer and survival: median survival was 19 months for the first group and 35 months for the second group (p=0.0398, 95% C.I), with 5-year overall survival rates 8% for patients diagnosed in the early 1990’s and 25% for patients diagnosed in the late 1990’s, p=0.0497. Two years survival was 25% and 60% respectively, although insignificant, p = 0.0941. Although there was no significant difference in number of chemotherapy courses given in the 2 groups, many more new generation treatments were used for the late 90th group. The Hazard of death within 5 years for patients treated with at least one new generation protocol was 0.53, p= 0.004. Conclusions: This study suggests that there has been significant survival improvement in breast cancer patients diagnosed with synchronous metastasis during the second half of the 1990’s. This improvement can be explained by the introduction of new treatments agents and strategies during the last decade No significant financial relationships to disclose.

Elevated pretreatment serum activin A and progression-free and overall survival in trastuzumab-treated metastatic breast cancer.

2012 ◽  
Vol 30 (30_suppl) ◽  
pp. 38-38
Author(s):  
Lindsey Zubritsky ◽  
Kim Leitzel ◽  
Suhail M. Ali ◽  
Wolfgang Köstler ◽  
Eva-Maria Fuchs ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Metastatic Breast ◽  
Activin A ◽  
Breast Cancer Patients ◽  
First Line ◽  
Pretreatment Serum

38 Background: About half of HER2-positive metastatic breast cancer patients will respond tofirst-line trastuzumab-containing therapy, but most will progress within a year. Trastuzumab resistance remains a vexing clinical problem, and better predictive and prognostic biomarkers are needed. Activin A is a TGF-B superfamily member and regulates cell proliferation, apoptosis, differentiation, and immune response. Methods: Serum activin A was measured using ELISA (R&D Systems, Minneapolis, MN) in 60 metastatic breast cancer patients before starting first-line trastuzumab-containing therapy. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox modeling with both continuous and dichotomous (median) serum activin A analyses. Results: Pretreatment serum activin A levels averaged 2376 pg/ml, and had a median of 629 pg/ml and 25th and 75th quartile values of 406 and 1791 pg/ml, respectively. Patients who were hormone receptor negative had significantly higher activin A levels (median 1287 vs 450 pg/ml, p=0.002). Higher serum activin A was significant on a continuous basis for predicting reduced PFS to first-line trastuzumab-containing therapy (p<0.003), and for predicting shorter OS (p<0.0001). When analyzed using a dichotomous (median) cutpoint, the elevated serum activin A cohort had a significantly reduced PFS (HR 2.79, p <0. 002) (median 6.6 mo vs. 31.1 mo) and OS (HR 5.24, p <0.0001) (median 19.6 mo vs. median not reached). In multivariate analysis for PFS with other covariates (age, line of therapy, CA 15-3, and hormone receptor status), activin A was the only significant covariate (p=0.021). In multivariate analysis for OS, activin A (p=0.002) and CA 15-3 (p=0.03) remained significant as prognostic factors. Conclusions: Elevated pretreatment serum activin A predicts reduced PFS and overall survival in metastatic breast cancer patients treated with first-line trastuzumab-containing therapy. Activin A deserves further study as an adverse biomarker, and to select patients most likely to respond to activin A-targeted therapy.

scholarly journals TFF1andTFF3mRNAs Are Higher in Blood from Breast Cancer Patients with Metastatic Disease than Those without

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Marwa H. Elnagdy ◽  
Omar Farouk ◽  
Amal K. Seleem ◽  
Hoda A. Nada
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Cancer Metastasis ◽  
Lung Metastases ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Significant Difference ◽  
High Level

Introduction. Breast cancer metastasis occurs when tumor cells dissociate from the primary tumor and migrate to distant organs through the peripheral bloodstream or lymphatic drainage. Circulating tumor cells (CTCs) originate from primary sites or metastases and circulate in the patients’ bloodstream. Molecular assays for the detection and molecular characterization of CTCs can serve as a liquid biopsy and can represent an alternative to invasive biopsies as a source of tumor tissue in the metastatic patients.Patients and Methods. We analyzed the presence of CTCs in the peripheral blood of 50 breast cancer patients by quantitative real-time reverse transcriptase polymerase chain reaction (RT-qPCR) to detecttrefoil factor family(TFF)1and3genes.Results. We found significant difference in the level of bothTFF1andTFF3mRNA in the blood of nonmetastatic versus metastatic breast cancer patients (p=0.001 and p= 0.038, respectively).TFF1mRNA was detected at higher levels in 34.6% of metastatic breast cancer patients as compared to 0% of nonmetastatic (p= 0.002). As regardsTFF3mRNA, it was detected at higher levels in 46.2% of metastatic breast cancer patients as compared to 4% of nonmetastatic (p= 0.026). Moreover, we found that the high level of bothTFF1andTFF3mRNA was related to estrogen status of the patients. The detection of high level ofTFF1mRNA in CTCs was associated with bone metastases (77.8%), while that ofTFF3was related to lymph node involvement (75%) and lung metastases (68.8%).Conclusion. The combined measurement of bothTFF1andTFF3mRNA level for differentiation of metastatic from nonmetastatic breast cancer gave 57.69% sensitivity and 83.3% specificity.

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