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.

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]

A randomised phase 2 study of 3 weekly cabazitaxel vs weekly paclitaxel chemotherapy in the first-line treatment of HER2 negative metastatic breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS1122-TPS1122
Author(s):  
Amit Bahl ◽  
Jeremy Braybrooke
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Phase 2 ◽  
First Line ◽  
Phase 3 ◽  
Early Stage Disease ◽  
Phase 2 Study ◽  
Her 2

TPS1122 Background: Breast cancer (BC) represents 25% of all cancers in women. Whilst the majority have early stage disease approximately 30% will develop metastatic breast cancer (MBC). In HER2 negative MBC, palliative chemotherapy is one of the main treatment options. It remains to be seen whether the use of adjuvant taxane chemotherapy leads to an increase in taxane resistance at the onset of MBC, although for patients with a relatively short disease free interval this may be the case. Cabazitaxel (CBZ) is a novel taxoid selected for development from preclinical evidence in cell lines resistant to docetaxel and paclitaxel including activity in a HER-2 positive BC tumour xenograft, with innate resistance to docetaxel. Clinically CBZ is licensed for metastatic castration-resistant prostate cancer following progression during or after docetaxel chemotherapy. A phase 3 RCT in this patient group showed a 3 month overall survival benefit for patients receiving CBZ and prednisolone compared with mitoxantrone and prednisolone. Methods: CONCEPT is an open label randomised phase 2 trial of first line chemotherapy in patients with HER-2 negative MBC where paclitaxel would be considered the standard treatment. Patients are randomised to cabazitaxel 25 mg/m2 every 21 days for 6 cycles or paclitaxel 80 mg/m2 weekly for 18 weeks. Eligibility includes patients who are PS 0 or 1 who may have received prior docetaxel in the adjuvant setting or be taxane-naïve. The primary endpoint is progression free survival (PFS), defined as the time between the date of randomisation and progression (according to RECIST version 1.1) or death from any cause. Secondary end-points include safety, overall survival and assessment of quality of life factors by FACT-B and EQ-5D-5L. For the current phase 2 study 90 patients will be recruited, with a 1:1 randomisation, proceeding to phase 3 of 160 patients, if the interim analysis does not show futility. To date 38 patients have been recruited from 10 centres. The IDMC met in Oct 2016 and recommended the study continue recruitment.

Eribulin improved overall survival in patients with HER-2 negative metastatic breast cancer: Comparison to bevacizumab plus paclitaxel.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e12035-e12035 ◽  
Author(s):  
Mitsuhiko Iwamoto ◽  
Nodoka Umezaki ◽  
Juuna Matsuda ◽  
Kanako Kawaguchi ◽  
Risa Terasawa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Her 2

Treatment Strategy for Patients with HR-Positive HER2-Negative Metastatic Breast Cancer That Progressed on CDK4/6 Inhibitors

Breast Care ◽  
2021 ◽  
pp. 1-8
Author(s):  
Shouko Hayama ◽  
Rikiya Nakamura ◽  
Toshiko Miyaki ◽  
Makiko Itami ◽  
Naohito Yamamoto
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Treatment Option ◽  
Metastatic Breast ◽  
Mtor Inhibitors ◽  
Subsequent Treatment ◽  
Rank Test ◽  
Significant Difference ◽  
Group A ◽  
Group B

<b><i>Background/Aims:</i></b> The study aim was to evaluate if mTOR inhibitors can be considered as a treatment option for HR+ HER2− metastatic breast cancer (MBC) after progression on CDK4/6 inhibitors in clinical practice. <b><i>Methods:</i></b> We retrospectively collected the clinicopathological data of patients with HR+ HER2− MBC treated with CDK4/6 inhibitors and subsequent therapies at our institution between 2014 and 2020. The patients were divided into 3 groups according to the type of subsequent treatment: (A) exemestane plus everolimus, (B) endocrine monotherapy, and (C) chemotherapy. Overall survival (OS) was estimated by using the Kaplan-Meier method and compared by using the log-rank test. The efficacy and adverse events (AEs) of each subsequent treatment were assessed by using Fisher’s exact tests. <b><i>Results:</i></b> Eighty-six patients (34 in group A, 20 in group B, 32 in group C) were included. The most common endocrine therapy in group B was fulvestrant (40%). The major chemotherapy regimen in group C was eribulin (25%). The median OS times after stopping CDK4/6 inhibitors were 34.5 months (95% confidence interval, 17.2 to NA), 13.6 months (3.9 to NA), and 19.5 months (18.8 to NA) in group A, group B, and group C, respectively. The only significant difference in OS was observed between group A and group B (20.9 months; <i>p</i> = 0.003). There was no difference in the incidence of grade 3 AEs between groups A and C or in the frequency of treatment discontinuation because of AEs among the 3 groups. <b><i>Conclusion:</i></b> Our study shows that mTOR inhibitors might be an effective treatment option for patients with HR+ HER2− MBC previously treated with CDK4/6 inhibitors.

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]

Chromosome 17 polysomy and Her-2/neu status in metastatic breast cancer patients indicated to trastuzumab therapy

2005 ◽  
Vol 23 (16_suppl) ◽  
pp. 9584-9584 ◽  
Author(s):  
M. Hajduch ◽  
R. Trojanec ◽  
K. Bouchalova ◽  
Z. Kolar ◽  
K. Petrakova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Metastatic Breast ◽  
Chromosome 17 ◽  
Breast Cancer Patients ◽  
Trastuzumab Therapy ◽  
Her 2

Metastatic breast cancer treated by chemotherapy: Trends in survival and costs in two patient cohorts treated in 1994–1998 and 2003–2006

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6552-6552
Author(s):  
G. Galy ◽  
S. Labidi ◽  
D. Perol ◽  
C. Carol ◽  
J. Guastalla ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Survival Data ◽  
Cox Regression ◽  
Metastatic Breast ◽  
Chemotherapeutic Agents ◽  
Cox Regression Analysis ◽  
Her 2

6552 Background: Although new chemotherapy agents have been approved during the past decade for the treatment of metastatic breast cancer (MBC), it is unclear whether their use has changed the outcome of patients. This study assessed the clinical and economic impacts of these drugs. Methods: We undertook a retrospective study of women diagnosed with MBC during two periods of time, 1994–1998 and 2003–2006 and compared overall survival data between the two groups. Female patients with MBC were identified from the Centre Léon Bérard (Lyon, France) database. Tumor and treatment characteristics, costs of chemotherapy, and patient outcome were compared using the X2 test, the log rank test, and Cox regression analysis. Overall survival was calculated from the date of MBC diagnosis to the date of death or last follow-up. Chemotherapy-related costs were calculated according to the 2008 pricelist of French cancer centers. Results: A total of 301 MBC cases were identified. The median follow-up of living patients was 3.87 years. No survival difference was observed between the two periods, with a median overall survival of 2.76 years for the 1994–1998 cohort (149 patients) and 2.68 years for the 2003–2006 cohort (152 patients) (HR 1.04, 95%CI 0.70–1.55; p = 0.83). The median number of lines of chemotherapy was similar in the two groups (=3). The median cost of chemotherapy per MBC patient was 3 times higher in 2003–2006 (25,320 €) than in 1994–1998 (8,865 €; p < 0.001). In multivariate analysis, prognostic factors for overall survival were the number of metastatic sites (HR 2.06; p < 0.0001), bone metastases (HR 0.67; p = 0.007), and hormone receptors (HR 0.56; p = 0.002). Survival was identical in HER-2 positive and HER-2 negative patients (HR 0.99; p = 0.99). Conclusions: Despite the implementation of numerous novel chemotherapeutic agents, the overall survival of patients with metastatic breast cancer has not improved over the last decade on the scale of our institution, whereas the costs of chemotherapy have significantly increased. No significant financial relationships to disclose.

Trastuzumab plus capecitabine and docetaxel as first-line therapy for metastatic breast cancer: Phase II results

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1111-1111
Author(s):  
C. G. Gennatas ◽  
V. Michalaki ◽  
S. Gennatas
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Adverse Events ◽  
Survival Time ◽  
Metastatic Breast ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Her 2

1111 Background: In human epidermal growth factor 2 (HER-2)-positive advanced breast cancer, taxanes plus trastuzumab are among the most widely applied options in the first-line setting. The addition of capecitabine to docetaxel significantly improves overall survival in anthracycline-pretreated metastatic breast cancer. We evaluated the efficacy and tolerability of trastuzumab plus capecitabine and docetaxel regimen as first-line therapy. Methods: Patients who had received adjuvant anthracyclines received docetaxel 75 mg/m2 day 1 and capecitabine 950 mg/m2 twice daily, days 1–14, every 3 weeks until disease progression or unacceptable toxicity. Trastuzumab was administered at a dose of 6 mg/kg every 3 weeks. Time to progression (TTP) was defined as primary end point. Results: Twenty eight patients were evaluable (median age 52 years, range 34–70). The regimen achieved objective responses in 11 patients (39%), including complete response in three patients (11%) and partial response in eight patients (28.5%). The median overall survival time was 25.5 months, and the median progression-free survival time was 7.8 months. The safety profile of the combination was favorable and predictable, with a low incidence of grade 3/4 adverse events. The most common adverse events were hand-foot syndrome, and GI toxicities. Severe myelosuppression was rare and cardiac toxicity did not occur. Conclusions: These data confirm that the combination of trastuzumab plus capecitabine and docetaxel is highly active in patients with HER-2-overexpressing anthracycline-pretreated breast cancer, and is well tolerated. No significant financial relationships to disclose.

Comparison of Methods of Measuring HER-2 in Metastatic Breast Cancer Patients Treated With High-Dose Chemotherapy

2001 ◽  
Vol 19 (6) ◽  
pp. 1698-1706 ◽  
Author(s):  
Lyndsay N. Harris ◽  
Vlayka Liotcheva ◽  
Gloria Broadwater ◽  
Michael J. Ramirez ◽  
Peter Maimonis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Prognostic Factor ◽  
Alkylating Agents ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
High Dose ◽  
Breast Cancer Patients ◽  
Her 2

PURPOSE: HER-2 is overexpressed in 20% to 30% of human breast cancer and is associated with poor outcome. Studies suggest an association between HER-2 overexpression and resistance to alkylating agents. To further evaluate this relationship, we assessed the interaction of HER-2, measured by different methods, and outcome after dose intensification with alkylating agents in metastatic breast cancer. PATIENTS AND METHODS: From 1988 to 1995 at Duke University, 425 patients with metastatic breast cancer were enrolled in a study of high-dose alkylating agents (HDC) with autologous cellular support after doxorubicin-based therapy (AFM). HER-2 was measured in serum for shed extracellular domain (ECD) and in tissue by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). RESULTS: HER-2 ECD was positive in 29% (19 of 65) of patients pre-AFM and in 11.7% (34 of 290) pre-HDC. Higher pre-AFM and higher pre-HDC HER-2 ECD predicted worse overall survival (P = .045 and P = .0096, respectively). HER-2 overexpression by IHC and FISH showed no correlation with worse disease-free survival or overall survival. FISH and ECD were highly specific for IHC (97.3% and 97.7% respectively). However, ECD had a low sensitivity for IHC—only 22% of patients with HER-2 in the primary tumor shed ECD into the serum. CONCLUSION: These data suggest that the method of measuring HER-2 is important in predicting clinical outcome. HER2 ECD may identify a poor prognosis subgroup of HER-2–positive tumors. Lack of association of HER2 by IHC/FISH with worse outcome suggests that therapy with AFM and/or HDC therapy may be able to overcome the effect of this prognostic factor or it may not be a prognostic factor in this setting.

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