Effect of tumor subtype on overall survival in brain metastatic breast cancer patients treated with cranial irradiation.

2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 74-74
Author(s):  
Vipin Das Villgran ◽  
Aju Mathew ◽  
Margaret Quinn Rosenzweig ◽  
Shira Abberbock ◽  
Rohan Dilipbhai Naik ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Breast Cancer Subtype ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Tumor Subtype ◽  
Prognostic Role ◽  
Tumor Subtypes ◽  
Significant Difference

74 Background: Brain metastatic breast cancer (BMBC) is often treated with whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS) or both. Breast cancer tumor subtypes defined by hormone receptor (HR) and HER2 status have an important prognostic role in metastatic disease. It is unclear if tumor subtypes have a prognostic role in patients receiving WBRT or SRS. We aimed to investigate the association between breast cancer subtype and overall survival (OS) among BMBC patients treated with WBRT and SRS. Methods: In a single-institution cohort study, BMBC patients treated with WBRT/SRS during 1997-2013 were identified. Clinico-pathological characteristics and survival information were prospectively collected. Tumor subtype category were defined as HR+/HER2-, HER2+/HR+, HER2+/HR- and triple negative (TN). WBRT category patients received that modality and SRS category patients, only SRS for treatment of brain metastases. OS is defined as time from diagnosis of brain metastasis to death or last follow-up. We conducted univariate analyses using the Kaplan-Meier method and log-rank tests and multivariate analysis using Cox proportional hazards models. Results: Among 193 BMBC patients who received WBRT or SRS, 62 received just SRS, and among them, 45% was HR+/HER2-. The distribution of subtypes was similar in WBRT patients. The median OS in SRS group was 15 months (95% CI 11-18) compared to WBRT with 10 months (95% CI 7-14) (p=0.03). Among patients receiving WBRT, median OS in HER2+/HR- tumor was 30 months (95% CI 13-37), HER2+/HR+ tumor - 14 months (95% CI 5-24), HER2-/HR+ tumor - 8 months (95% CI 4-11) and TN - 5 months (95% CI 3-9) (P=0.0003). There was no significant difference in OS between the breast cancer subtypes among SRS patients: median OS among patients with HER2+/HR- tumor was 11 months (95% CI 5–27), HER2+/HR+ tumor - 25 months (95% CI 7-32), HER2-/HR+ tumor - 18 months (95% CI 14-32), and TN - 12 months (95% CI 3-24) (p=0.07). Conclusions: Among patients with BMBC,tumor subtype is a prognostic factor for survival in those who received WBRT. Tumor subtype provided no prognostic information for those who were treated with only SRS.

Paclitaxel plus carboplatin versus paclitaxel plus epirubicin as first-line treatment for metastatic breast cancer: Efficacy and safety results of a randomized, phase III trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1087-1087
Author(s):  
Zhongsheng Tong ◽  
Shufen Li ◽  
Yehui Shi ◽  
Xu Wang ◽  
Chen Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Free Survival ◽  
Significant Difference

1087 Background: Paclitaxel/carboplatin combinations are highly active in metastatic breast cancer (MBC). We conducted a randomized, phase III, non-inferiority trial comparing paclitaxel/carboplatin (TP) with paclitaxel/epirubicin (TE) as first-line therapy for MBC. Progression-free survival (PFS) was the primary efficacy endpoint. Secondary endpoints included response rate, overall survival, tolerability, and quality of life (QoL). Methods: From June 2009 to January 2015, 231 patients were randomly assigned, 115 of whom were randomized to TP and 116 to TE. Baseline characteristics were relatively well-balanced in the two treatments. Results: After a median follow-up of 29 months, no significant difference was observed between the two treatments in objective response rate (ORR) (38.3% vs. 39.7%, respectively). Both the progression-free survival (p=0.158) and overall survival (p=0.369) were very similar between the two treatments. Both regimens were well tolerated. The main toxicities were myelosuppression, gastrointestinal reactions, and alopecia. TP showed higher grades 3–4 alopecia and higher nausea (p<0.05). TE showed higher incidence of myelosuppression than TP (p<0.05) (Table). Those patients whose epirubicin cumulative dose was more than 1000 mg/m2 did not suffer worse cardiotoxicity. Conclusions: Our study suggests that TP arm is an effective therapeutic alternative for patients with MBC, especially in those previously exposed to epirubicin in the adjuvant setting. TP has some advantages, such as less cost and less side effects (myelosuppression and fatigue). Clinical trial information: NCT02207361. [Table: see text]

Use of the ErbB2/CEP17 ratio to predict prognosis and response to trastuzumab-based therapy in the metastatic breast cancer setting

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11110-11110
Author(s):  
E. Fuchs ◽  
W. Köstler ◽  
R. Horvath ◽  
G. Hudelist ◽  
E. Kubista ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Copy Number ◽  
Metastatic Breast ◽  
Chromosome 17 ◽  
Fish Analysis ◽  
Significant Difference ◽  
Group A ◽  
Her 2

11110 Background: Despite patient selection based upon detection of Her-2/neu overexpression by immunohistochemistry (IHC) and/or presence of amplification of the Her-2/neu-encoding erbB2 oncogene measured by FISH, response to trastuzumab-based therapy is only achieved in a subset of patients with Her-2/neu overexpressing breast carcinomas. Exact quantification of erbB2 copy-number relative to chromosome 17 (CEP17) (ErbB2/CEP17 ratio “R”) probably adds further important predictive information. Methods: Clinical data of 137 patients receiving trastuzumab based treatment for Her-2/neu overexpressing (IHC) metastatic breast cancer were analysed. ErbB2/CEP17 ratio (R) was determined by quantitative FISH analysis in original tumor tissue using Vysis PathVysion DNA-based FISH technology. Results: ErbB2/CEP17 (R) provided additional predictive value for progression free survival (PFS) and time to first metastasis (TTM), but not for overall survival (OS) (all from start of trastuzumab containing treatment). The following cutoffs of Her-2/neu were identified: group A: 0–2.2 R (TTM: 49.8; OS: 6.7; PFS: 6.2); group B: 2.2- 6 R (TTM: 26.2; OS: 5.3; PFS: 9.3); group C: >6 CN (TTM: 20.1; OS: 3.9; PFS: 13.7) Kaplan-Maier analysis showed significant longer TTM for group A (p<0.01 vs. B/C), significant longer PFS for group C (p<0.01 vs. A/B). Significant differences in complete response (B/C: 16.9% vs C:44.4%), partial response (B/C: 20.2% vs. C: 33.3%) and progressive disease (B/C: 27% vs. 11.1%) were noted. No significant difference in overall survival between the groups was seen. Conclusions: ErbB/CEP17 R provides important prognostic information and, in metastatic patients, allows one to better predict response to trastuzumab-based treatment than the widely used binary classification of ErbB2 amplification that is based on a cut-off at a copy number of >2.2. No significant financial relationships to disclose.

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]

Association of the neutrophil to lymphocyte ratio with survival patients with in metastatic breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11544-e11544
Author(s):  
Ozan Unlu ◽  
Sevda Aygun ◽  
Hilbrahim Petekkaya ◽  
Gizem Gecmez ◽  
Emir C. Roach ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Neutrophil To Lymphocyte Ratio ◽  
Breast Cancer Patients ◽  
Lymphocyte Ratio ◽  
Significant Difference

e11544 Background: Identification of simple and measurable prognostic factors is an important issue in treatment evaluation of breast cancer. Although various markers are considered while making a decision to treatment modality, clinicians investigate for new prognostic factors for reason of highly variable responses of individuals. Therefore, this study estimates the survival probability of the neutrophil to lymphocyte ratio (NLR) for patients with metastatic breast cancer. Methods: We included the patients with metastatic breast carcinoma who were treated for metastasis. NLR were calculated and patients were divided into four quartiles (25th, 50th and 75th NLR; the lowest being the 1st quartile, the highest being 4th quartile ). Survival status was retrieved from our cancer registry. Survival analysis, stratified by NLR quartiles, was used to evaluate the predictive value of NLR. Results: Eighty-one patients with metastatic breast cancer were included in this study. Median age of diagnosis of the patients was 47 (26-83), the majority of them had grade II (%37) and grade III (%29.6) tumors and were metastatic at the time of their initial diagnosis. ER (+), PR (+) and HER2 (+) percentages were confirmed as 82%, 73% and 24% ,respectively. Ten percent of the patients were triple negative. Median follow-up time was 26 months and 29 patients died during the follow up period. We analyzed the overall survival among NLR quartiles. When we compared the quartiles with the highest and lowest NLR values, the quartile with the lowest NLR values had longer median overall survival than the quartile with the highest NLR values (212 vs. 27 months; p=0.01). The second and third quartiles, however, showed no statistically significant difference of overall survival between four quartiles. Conclusions: NLR can be a prognostic factor for overall survival in metastatic breast cancer patients.

scholarly journals Single arm, phase two study of low-dose metronomic eribulin in metastatic breast cancer

2021 ◽  
Author(s):  
Pavani Chalasani ◽  
Kiah Farr ◽  
Vicky Wu ◽  
Isaac Jenkins ◽  
Alex Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Peripheral Neuropathy ◽  
Clinical Benefit ◽  
Low Dose ◽  
Response Rate ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Free Survival

Abstract Background Treatment options for metastatic breast cancer (MBC) refractory to anthracyclines and taxanes are limited. In a phase III trial, eribulin demonstrated a significant improvement in overall survival compared to treatment of physician’s choice, but had limited tolerability because of neutropenia and peripheral neuropathy. Based on prior studies of alternative treatment schedules with other therapies, we hypothesized that a low-dose metronomic schedule of eribulin would permit patients to remain on treatment more consistently without treatment delays, resulting in longer time to progression, and improved toxicity profile. Methods We conducted a multi-site single arm, phase II trial patients with MBC. All patients were treated with metronomic eribulin (0.9 mg/m2 administered intravenously on days 1, 8, and 15 of a 28-day cycle.) Treatment was continued until the patient developed disease progression, unacceptable toxicity, or chose to stop the study. Patients must have had prior taxane exposure. The primary endpoint was progression-free survival. Secondary end points were overall survival, response rate, and clinical benefit rate. Exploratory biomarkers were performed to analyze change in levels of circulating endothelial cells (CECs), circulating endothelial precursors, and carbonic anhydrase IX (CAIX) with response to therapy. Findings We consented 86 patients and 59 were evaluable for final analysis. Median age was 59 years; 78% had HER2 negative tumors. The median progression-free survival (PFS) was 3.5 months with overall survival (OS) of 14.3 months. Objective response rate was 15% with clinical benefit rate of 48%. Reported grade 3 neutropenia and peripheral neuropathy were 18% and 5%, respectively. Treatment discontinuation due to toxicity was seen in 3% of patients. Interpretation Metronomic weekly low-dose eribulin is an active and tolerable regimen with significantly less myelosuppression, alopecia, and peripheral neuropathy than is seen with the approved dose and schedule, allowing longer duration of use and disease control, with similar outcomes compared to the standard dose regimen.

scholarly journals Integrative statistical analyses of multiple liquid biopsy analytes in metastatic breast cancer

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Corinna Keup ◽  
Vinay Suryaprakash ◽  
Siegfried Hauch ◽  
Markus Storbeck ◽  
Peter Hahn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Mutual Information ◽  
Hierarchical Clustering ◽  
Liquid Biopsy ◽  
Metastatic Breast ◽  
The Other ◽  
Theoretic Analysis ◽  
Graph Theoretic

Abstract Background Single liquid biopsy analytes (LBAs) have been utilized for therapy selection in metastatic breast cancer (MBC). We performed integrative statistical analyses to examine the clinical relevance of using multiple LBAs: matched circulating tumor cell (CTC) mRNA, CTC genomic DNA (gDNA), extracellular vesicle (EV) mRNA, and cell-free DNA (cfDNA). Methods Blood was drawn from 26 hormone receptor-positive, HER2-negative MBC patients. CTC mRNA and EV mRNA were analyzed using a multi-marker qPCR. Plasma from CTC-depleted blood was utilized for cfDNA isolation. gDNA from CTCs was isolated from mRNA-depleted CTC lysates. CTC gDNA and cfDNA were analyzed by targeted sequencing. Hierarchical clustering was performed within each analyte, and its results were combined into a score termed Evaluation of multiple Liquid biopsy analytes In Metastatic breast cancer patients All from one blood sample (ELIMA.score), which calculates the contribution of each analyte to the overall survival prediction. Singular value decomposition (SVD), mutual information calculation, k-means clustering, and graph-theoretic analysis were conducted to elucidate the dependence between individual analytes. Results A combination of two/three/four LBAs increased the prevalence of patients with actionable signals. Aggregating the results of hierarchical clustering of individual LBAs into the ELIMA.score resulted in a highly significant correlation with overall survival, thereby bolstering evidence for the additive value of using multiple LBAs. Computation of mutual information indicated that none of the LBAs is independent of the others, but the ability of a single LBA to describe the others is rather limited—only CTC gDNA could partially describe the other three LBAs. SVD revealed that the strongest singular vectors originate from all four LBAs, but a majority originated from CTC gDNA. After k-means clustering of patients based on parameters of all four LBAs, the graph-theoretic analysis revealed CTC ERBB2 variants only in patients belonging to one particular cluster. Conclusions The additional benefits of using all four LBAs were objectively demonstrated in this pilot study, which also indicated a relative dominance of CTC gDNA over the other LBAs. Consequently, a multi-parametric liquid biopsy approach deconvolutes the genomic and transcriptomic complexity and should be considered in clinical practice.

scholarly journals Phenotypic discordance between primary and metastatic breast cancer in the large-scale real-life multicenter French ESME cohort

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Thomas Grinda ◽  
Natacha Joyon ◽  
Amélie Lusque ◽  
Sarah Lefèvre ◽  
Laurent Arnould ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Large Scale ◽  
Tumour Progression ◽  
Primary Tumour ◽  
Multivariable Analysis ◽  
Real Life ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Risk Of Death

AbstractExpression of hormone receptor (HR) for estrogens (ER) and progesterone (PR) and HER2 remains the cornerstone to define the therapeutic strategy for breast cancer patients. We aimed to compare phenotypic profiles between matched primary and metastatic breast cancer (MBC) in the ESME database, a National real-life multicenter cohort of MBC patients. Patients with results available on both primary tumour and metastatic disease within 6 months of MBC diagnosis and before any tumour progression were eligible for the main analysis. Among the 16,703 patients included in the database, 1677 (10.0%) had available biopsy results at MBC diagnosis and on matched primary tumour. The change rate of either HR or HER2 was 27.0%. Global HR status changed (from positive = either ER or PR positive, to negative = both negative; and reverse) in 14.2% of the cases (expression loss in 72.5% and gain in 27.5%). HER2 status changed in 7.8% (amplification loss in 45.2%). The discordance rate appeared similar across different biopsy sites. Metastasis to bone, HER2+ and RH+/HER2- subtypes and previous adjuvant endocrine therapy, but not relapse interval were associated with an HR discordance in multivariable analysis. Loss of HR status was significantly associated with a risk of death (HR adjusted = 1.51, p = 0.002) while gain of HR and HER2 discordance was not. In conclusion, discordance of HR and HER2 expression between primary and metastatic breast cancer cannot be neglected. In addition, HR loss is associated with worse survival. Sampling metastatic sites is essential for treatment adjustment.

Early change in tumour size predicts overall survival in patients with first-line metastatic breast cancer

2016 ◽  
Vol 66 ◽  
pp. 95-103 ◽  
Author(s):  
Sonya C. Tate ◽  
Valerie Andre ◽  
Nathan Enas ◽  
Benjamin Ribba ◽  
Ivelina Gueorguieva
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Tumour Size ◽  
Metastatic Breast ◽  
First Line ◽  
Early Change

Survival outcomes in patients with IDC and ILC breast cancer: A well matched single institution study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13056-e13056
Author(s):  
Michael Grimm ◽  
Bhuvaneswari Ramaswamy ◽  
Maryam B. Lustberg ◽  
Robert Wesolowski ◽  
Sagar D. Sardesai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Metastatic Breast ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Her2 Status ◽  
Single Institution ◽  
First Line ◽  
Response To Chemotherapy ◽  
Significant Difference

e13056 Background: Invasive lobular carcinoma (ILC) accounts for only 10-15% of all invasive breast cancers but has distinct clinicopathologic characteristics and genomic profiles. In particular, metastatic lobular cancers (mILC) have unique sites of metastasis and it is unclear if the response to initial endocrine therapy differs from metastatic ductal cancers (mIDC). Therefore we have undertaken a single-institution, retrospective analysis to compare overall outcomes and response to initial endocrine therapy (ET) in patients (pts) with metastatic ILC and IDC. Methods: An IRB approved retrospective review of medical records was conducted evaluating pts treated for metastatic IDC and ILC at The Ohio State University Comprehensive Cancer Center from January 1, 2004 to December 31, 2014. Pts diagnosed with mIDC were matched on age, year of diagnosis, estrogen receptor/progesterone receptor and HER2 status and site of metastasis 2:1 to patients diagnosed with mILC. Overall survival (OS) was defined as the time from metastasis to death or last known follow-up. Progression-free survival (PFS) was defined as time from metastasis to progression on first-line ET. Time to chemotherapy (TTC) was defined as time from starting ET for metastasis to initiation of chemotherapy. Kaplan Meier (KM) methods were used to calculate median OS, PFS and TTC. Results: A total of one hundred sixty one pts with metastatic breast cancer were included in this analysis. The demographic features between the two groups were well balanced and included in the table below. The median OS was 2.6 yrs (95% CI: 1.55, 3.22) for mILC and 2.2 yrs (95% CI: 1.95, 2.62) for mIDC. A subset of 111 patients who started on endocrine therapy were used in the PFS and TTC analyses. The median PFS following first-line ET was 2.2 yrs (95% CI: 0.1.0, 2.7) for mILC and 1.4 yrs (95% CI: 0.91, 1.90) for mIDC. Median TTC was 2.1 yrs (95% CI: 1.71, 4.92) for mILC and 2.4 yrs (95% CI: 1.90, 4.77) for mIDC. There was no statistically significant difference in outcomes between the two groups. Conclusions: Outcomes in patients with ILC and IDC have been varied, with several studies reporting that patients with ILC have worse outcomes and response to chemotherapy. Our retrospective study examining outcomes in mILC in comparison with mIDC showed no difference in OS. Given the concern of resistance to conventional therapies in patients with lobular cancers, it is reassuring to see that the median PFS on first line ET and TTC was similar to metastatic ductal cancers.[Table: see text]

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