Relationship between Quantitative HER2 Protein Expression and Clinical Outcomes in ER-Positive and ER-Negative Sub-Groups of Patients with Trastuzumab-Treated Metastatic Breast Cancer.

2009 ◽  
Author(s):  
M. Bates ◽  
J. Sperinde ◽  
K. Leitzel ◽  
S. Ali ◽  
S. Ali ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Protein Expression ◽  
Clinical Outcomes ◽  
Metastatic Breast ◽  
Her2 Protein ◽  
Er Positive

HER2 expression and HER2:HER2 dimerization identifies subpopulations of metastatic breast cancer patients with different probabilities of long-term survival following trastuzumab treatment and with different requirements for concomitant chemotherapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10557-10557 ◽  
Author(s):  
M. P. Bates ◽  
C. Desmedt ◽  
J. Sperinde ◽  
W. Huang ◽  
D. Larsimont ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Protein Expression ◽  
Metastatic Breast ◽  
Her2 Overexpression ◽  
Her2 Expression ◽  
Concomitant Chemotherapy ◽  
Term Survival ◽  
Her2 Protein ◽  
Trastuzumab Treatment

10557 Background: Selection of patients for treatment with trastuzumab is currently based on the semi-quantitative measurement of HER2 protein expression (IHC) or gene amplification (FISH). We made quantitative measurements of HER2 expression and homodimerization using a novel assay, eTag, and correlated them with overall survival (OS) and time-to-progression (TTP) following trastuzumab treatment in a cohort of patients with metastatic breast cancer (MBC). We also examined the benefit of concomitant chemotherapy (CT) depending on quantitative HER2 expression. Methods: The Jules Bordet cohort (Brussels, Belgium, N=71) had MBC and prior treatment with at least two CT regimens. Patients received trastuzumab alone or combined with predominantly paclitaxel. Independent medical data review and central confirmation of HER2 overexpression by FISH (N=64) or IHC (N=7) were mandatory. The eTag assay was used to quantitate HER2 protein expression and HER2:HER2 dimers in FFPE specimens. eTag measurements were correlated with OS and TTP using Kaplan-Meier and Cox Proportional Hazards regression analyses. Results: Cox analyses identified three independent correlates of OS and TTP: number of metastatic sites (HROS = 2.4/site, 95%CI 1.5–3.9, p = 0.00019), treatment with trastuzumab only (HROS = 2.8, 95%CI 1.1–7.3, p = 0.036), and HER2 expression level (HROS = 0.24/log10(HER2), 95%CI 0.09–0.7, p = 0.0058). Patients with high HER2 (above median expression) experienced better OS than those with low HER2 (HR 0.24, p = 0.0014). Patients with high HER2 expression did not benefit from added CT (HR = 0.95, 95%CI 0.24–3.8, p = 0.94), while patients with low HER2 expression did (trastuzumab alone HR 4.4, 95% CI 1.3–18, p = 0.018). Similar results were observed for HER2:HER2 dimerization. Conclusions: Within a population of patients selected by FISH or IHC to receive trastuzumab, higher HER2 expression or HER2:HER2 dimerization correlated with better outcomes. Patients with high HER2 expression derived no benefit from concomitant CT, while patients with low HER2 expression benefited significantly from the addition of CT to trastuzumab. No significant financial relationships to disclose.

scholarly journals Eribulin-trastuzumab combination in HER2-positive metastatic breast cancer: updated results from a Russian observational study

2021 ◽  
pp. 36-46
Author(s):  
E. I. Kovalenko ◽  
E. V. Artamonova ◽  
L. V. Bolotina ◽  
L. A. Zhiliaeva ◽  
D. M. Ponomarenko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Clinical Outcomes ◽  
Russian Federation ◽  
Metastatic Breast ◽  
Case Report Form ◽  
Her2 Positive ◽  
Optimal Drug ◽  
Er Positive ◽  
The Russian Federation

Introduction. The standard of 1st line treatment of HER2+ metastatic breast cancer (mBC) is double blockade with trastuzumab and pertuzumab + taxane, 2nd line – Trastuzumab-emtazine. There are no standards for further treatment, as well as the optimal drug sequence. Expansion of the arsenal of therapeutic possibilities and the use of new combinations will certainly improve the results of treatment of this category of patients and increase their life expectancy.Aim. We sought to describe treatment patterns of  eribulin  and clinical outcomes of  metastatic HER2-positive breast cancer treated with eribulin  plus trastuzumab combination in  academic institutions and community oncology practices across the Russian Federation.Materials and methods. Patients treated with eribulin anytime between Jan, 2014 and Sep, 2019 with a diagnosis of MBC were identified by 23 providers from Russia. Providers retrospectively reviewed the health records and abstracted selected data points into an electronic case report form for each eligible patient.Results. 100 HER2-positive pts received eribulin in combination with trastuzumab. Median age was 55 (31–80) yrs and ECOG status 0–3. 67% pts had visceral metastases. Eribulin was administered as 1st and 2nd line to 23 (23%) pts, 3rd line to 31 (31%) pts, 4th line and later to 46 (46%). Median number of cycles was 5 (2–27). ORR was 12%, SD – 72%, SD > 6 months – 23%, PD – 16%. Clinical efficacy rate achieved in 35%. Median PFS was 5.07 months (95% CI 4.021–6.119). According to the ER-status the response to eribulin and trastuzumab was different. ORR was 18.8%, SD 72.9% in pts with ER-positive MBC (n = 48) and 5.8% and 71.2% respectively in ER-negative MBC (n = 52). Median PFS was 6.97 months (95% CI 3.924–10.016) in pts with ER-positive MBC and 4.67 months (95% CI 3.841–5.499) in ER-negative MBC (р = 0.3). The combination was well tolerated: dose reductions were required in 12% pts, withdrawal due to toxicity in 4% pts. The most common type of toxicity was hematological with neutropenia Gr III-IV in 14 (14%) pts. Peripheral neuropathy Gr III was observed in 5 (5%) pts. No cardiotoxicity was detected.Conclusions. This is the real-life data of clinical outcomes for patients receiving eribulin plus trastuzumab for HER2-positive MBC throughout the Russian Federation. Our experience with eribulin plus trastuzumab demonstrates that this combination may be a potential effective treatment option for HER-2 positive MBC patients. 

scholarly journals HER3, p95HER2, and HER2 protein expression levels define multiple subtypes of HER2-positive metastatic breast cancer

2013 ◽  
Vol 141 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Allan Lipton ◽  
Laurie Goodman ◽  
Kim Leitzel ◽  
Jennifer Cook ◽  
Jeff Sperinde ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Protein Expression ◽  
Metastatic Breast ◽  
Her2 Positive ◽  
Her2 Protein ◽  
Expression Levels

scholarly journals Observational study of clinical outcomes of eribulin mesylate in metastatic breast cancer after cyclin-dependent kinase 4/6 inhibitor therapy

2019 ◽  
Vol 15 (34) ◽  
pp. 3935-3944 ◽  
Author(s):  
Sarah S Mougalian ◽  
Bruce A Feinberg ◽  
Edward Wang ◽  
Karenza Alexis ◽  
Debanjana Chatterjee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Clinical Outcomes ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Cyclin Dependent Kinase ◽  
Eribulin Mesylate ◽  
Free Survival

Aim: To examine the effectiveness of eribulin mesylate for metastatic breast cancer post cyclin-dependent kinase inhibitor (CDKi) 4/6 therapy. Materials & methods: US community oncologists reviewed charts of patients who had received eriublin from 3 February 2015 to 31 December 2017 after prior CDKi 4/6 therapy and detailed their clinical/treatment history, clinical outcomes (lesion measurements, progression, death) and toxicity. Results: Four patient cohorts were created according to eribulin line of therapy: second line, third line, per US label and fourth line with objective response rates/clinical benefit rates of 42.2%/58.7%, 26.1%/42.3%, 26.7%/54.1% and 17.9%/46.4%, respectively. Median progression-free survival/6-month progression-free survival (79.5% of all patients censored) by cohort was: 9.7 months/77.3%, 10.3 months/71.3%, not reached/70.4% and 4.0 months/0.0%, respectively. Overall occurrence of neutropenia = 23.5%, febrile neutropenia = 1.3%, peripheral neuropathy = 10.1% and diarrhea = 11.1%. Conclusion: Clinical outcome and adverse event rates were similar to those in clinical trials and other observational studies. Longer follow-up is required to confirm these findings.

Phase I/II trial of tamoxifen with or without fenretinide, an analog of vitamin A, in women with metastatic breast cancer.

1993 ◽  
Vol 11 (3) ◽  
pp. 474-477 ◽  
Author(s):  
M A Cobleigh ◽  
K Dowlatshahi ◽  
T A Deutsch ◽  
R G Mehta ◽  
R C Moon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Vitamin A ◽  
Phase I ◽  
Mammary Cancer ◽  
Metastatic Breast ◽  
Serum Levels ◽  
Phase Iii ◽  
Antitumor Effects ◽  
Er Positive

PURPOSE Considerable attention has been focused on the chemopreventive properties of fenretinide against carcinogen-induced rodent mammary cancer. Less is known about its direct antitumor effects. The combination of tamoxifen and fenretinide is more effective than tamoxifen or fenretinide alone in prevention of rat mammary cancer. However, the combined toxicity of tamoxifen plus fenretinide in humans is unknown. Therefore, we performed a phase I/II trial in women with estrogen receptor (ER)-positive or progesterone receptor (PR)-positive, previously untreated metastatic breast cancer. PATIENTS AND METHODS Groups of three patients received tamoxifen 20 mg/d, or tamoxifen plus fenretinide 100, 200, 300, or 400 mg/d. Patients who received fenretinide enjoyed a 3-day "drug holiday" every 4 weeks. Serum levels of fenretinide and its major metabolites were monitored. Patients were monitored for known toxicities of tamoxifen and vitamin A analogs, as well as for response. RESULTS There were no significant adverse effects on renal, hepatic, hematologic, or lipid values. Nyctalopia, photophobia, cheilitis, and pruritus were not observed. Improvement or stabilization of disease occurred in 12 of 15 patients. CONCLUSION We conclude that tamoxifen administered with fenretinide is nontoxic. Phase III trials of tamoxifen versus tamoxifen plus fenretinide are warranted.

scholarly journals Grade 3 Hepatotoxicity following Fulvestrant, Palbociclib, and Erdafitinib Therapy in a Patient with ER-Positive/PR-Negative/HER2-Negative Metastatic Breast Cancer: A Case Report

2020 ◽  
Vol 13 (1) ◽  
pp. 304-308 ◽  
Author(s):  
Alyssa Schlotman ◽  
Adam Stater ◽  
Kyle Schuler ◽  
Judd Heideman ◽  
Vandana Abramson
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Case Report ◽  
Metastatic Breast ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Hepatotoxic Effect ◽  
Er Positive ◽  
Grade 3 ◽  
Experienced Grade

A 49-year-old woman with ER-positive/PR-negative/HER2-negative metastatic breast cancer experienced Grade 3 hepatotoxicity following initiation of a clinical trial of fulvestrant, palbociclib, and erdafitinib. Fulvestrant was determined to be the drug most likely responsible for this hepatotoxic effect. This case report details the timing and nature of this drug-induced liver injury, adding support to an area that has yet to be described adequately in the existing literature.

Sign in / Sign up

Export Citation Format

Share Document