De-escalating adjuvant trastuzumab in human epidermal growth factor receptor 2 (HER2)-positive early-stage breast cancer: A systemic review and meta-analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 524-524
Author(s):  
Hadar Goldvaser ◽  
Korzets Ceder Yasmin ◽  
Daniel Shepshelovich ◽  
Rinat Yerushalmi ◽  
Michal Sarfaty ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cardiac Dysfunction ◽  
Early Stage ◽  
Nodal Involvement ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Trastuzumab Treatment ◽  
Her2 Positive Breast Cancer ◽  
One Year ◽  
Positive Breast Cancer

524 Background: One year of adjuvant trastuzumab in combination with chemotherapy is the standard of care in early-stage HER2 positive breast cancer. Existing data on shortening trastuzumab treatment show conflicting results. Methods: A search of PubMed and conferences identified randomized trials that compared abbreviated trastuzumab therapy to one year of treatment in early-stage HER2 positive breast cancer. Hazard ratios (HRs) and 95% confidence intervals (CI) were extracted for disease free survival (DFS) and overall survival (OS). Data on the number of DFS and distant relapse events were also collected as were the number of patients at risk in each group. Subgroup analyses evaluated the effect of nodal involvement, estrogen receptor (ER) expression and the duration of abbreviated trastuzumab (9-12 weeks versus 6 months). Odds ratios (ORs) and 95% CI were computed for pre-specified cardiotoxicity events including cardiac dysfunction and congestive heart failure (CHF). Results: Analysis included 6 trials comprising 11603 patients. In most studies adjuvant chemotherapy included anthracyclines and taxanes. Shorter trastuzumab treatment was associated with worse DFS (HR = 1.14, 95% CI 1.05-1.25, p = 0.002) and OS (HR = 1.15, 95% CI 1.02-1.29. p = 0.02). The effect on DFS was not influenced by ER status (p for the subgroup difference = 0.23), nodal involvement (p = 0.44) or the different duration of trastuzumab in the experimental arm (p = 0.08). In absolute terms, after an estimated median follow-up of 71 months, shorter treatment with trastuzumab was associated with an absolute increase in DFS events of 2.3%. Shorter trastuzumab treatment was associated with lower odds of cardiac dysfunction (OR = 0.67, 95% CI 0.55-0.81, p < 0.001) and CHF (OR = 0.66, 95% CI 0.50-0.86, p = 0.003). Conclusions: Compared to one year, shorter duration of adjuvant trastuzumab is associated with significantly worse DFS and OS, despite favorable cardiotoxicity profile. One year of trastuzumab should remain the standard adjuvant treatment in early-stage HER2 positive breast cancer with appropriate cardiac monitoring.

scholarly journals Deescalating Adjuvant Trastuzumab in HER2-Positive Early-Stage Breast Cancer: A Systemic Review and Meta-Analysis

2019 ◽  
Vol 3 (2) ◽  
Author(s):  
Hadar Goldvaser ◽  
Yasmin Korzets ◽  
Daniel Shepshelovich ◽  
Rinat Yerushalmi ◽  
Michal Sarfaty ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Heart Failure ◽  
Cardiac Dysfunction ◽  
Early Stage ◽  
Nodal Involvement ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Trastuzumab Treatment ◽  
One Year ◽  
Positive Breast Cancer

AbstractBackgroundOne year of adjuvant trastuzumab in combination with chemotherapy is the standard of care in early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Existing data on shortening trastuzumab treatment show conflicting results.MethodsA search of PubMed and abstracts from key conferences identified randomized trials that compared abbreviated trastuzumab therapy to 1 year of treatment in early-stage HER2-positive breast cancer. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted for disease-free survival (DFS) and overall survival (OS). Subgroup analyses evaluated the effect of nodal involvement, estrogen receptor expression, and the duration of abbreviated trastuzumab (9–12 weeks vs 6 months). Odds ratios (ORs) and 95% confidence intervals were computed for prespecified cardiotoxicity events including cardiac dysfunction and congestive heart failure. P values were two-sided.ResultsAnalysis included six trials comprising 11 603 patients. Shorter trastuzumab treatment was associated with worse DFS (HR = 1.14, 95% CI = 1.05 to 1.25, P  = .002) and OS (HR = 1.15, 95% CI = 1.02 to 1.29. P = .02). The effect on DFS was not influenced by estrogen receptor status (P for the subgroup difference = .23), nodal involvement (P = .44), or the different duration of trastuzumab in the experimental arm (P = .09). Shorter trastuzumab treatment was associated with lower odds of cardiac dysfunction (OR = 0.67, 95% CI = 0.55 to 0.81, P < .001) and congestive heart failure (OR = 0.66, 95% CI = 0.50 to 0.86, P = .003).ConclusionsCompared with 1 year, shorter duration of adjuvant trastuzumab is associated with statistically significantly worse DFS and OS despite favorable cardiotoxicity profile. One year of targeted HER2 treatment should remain the standard adjuvant treatment in early-stage HER2-positive disease with appropriate cardiac monitoring.

scholarly journals Do all patients with HER2 positive breast cancer require one year of adjuvant trastuzumab? A systematic review and meta-analysis

The Breast ◽  
2020 ◽  
Vol 54 ◽  
pp. 203-210
Author(s):  
Paul Stewart ◽  
Phillip Blanchette ◽  
Prakesh S. Shah ◽  
Xiang Y. Ye ◽  
R. Gabriel Boldt ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Meta Analysis ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Her2 Positive Breast Cancer ◽  
One Year ◽  
Positive Breast Cancer

Do all patients with HER2-positive breast cancer require one year of adjuvant trastuzumab?: A systematic review and meta-analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 522-522 ◽  
Author(s):  
Paul Stewart ◽  
Phillip S. Blanchette ◽  
Prakesh S Shah ◽  
Xiang Y Ye ◽  
R Gabriel Boldt ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Her2 Positive Breast Cancer ◽  
Er Positive ◽  
One Year ◽  
Positive Breast Cancer

522 Background: One year of adjuvant trastuzumab (T) remains the standard treatment for patients with HER2 positive breast cancer. Results from randomized trials with diverse non-inferiority margins comparing one year to a shorter duration of adjuvant T were not consistent, particularly with the PERSEPHONE and the final PHARE and Short-HER trials’ results. Our objective was to conduct a systematic review and meta-analysis of randomized trials in patients with HER2 positive breast cancer to assess whether a shorter duration of adjuvant T was non-inferior to one year of treatment. Methods: PubMed, EMBASE and The Cochrane Library were searched for eligible randomized trials. Hazard ratios (HR) for disease free and overall survival (DFS, OS) were weighted using generic inverse variance and pooled in a meta-analysis using random-effects models. The median of non-inferiority margins derived from each trial was calculated to set a non-inferiority margin of 1.29 for the pooled analysis. Subgroup analyses compared survival outcomes by estrogen receptor (ER) status, nodal status, length and timing of trastuzumab treatment. Results: Data of 11,376 patients from 5 trials were analyzed. A shorter duration of T was non-inferior to one year of therapy for DFS (HR 1.13, 95%CI 1.03-1.24) but worse for OS (HR 1.16, 95%CI 1.01-1.32). In addition, the non-inferiority for DFS was met for patients with ER positive disease (HR 1.1, 95%CI 0.95-1.28) and patients treated with 6 months (HR 1.09, 95%CI 0.98-1.22) or sequential T (HR 0.97, 95%CI 0.75-1.27). Conversely, the non-inferiority for DFS was not met for patients with ER negative disease (HR 1.22, 95%CI 1.06-1.41), patients treated with 9 weeks (HR 1.26, 95%CI 1.02-1.55) or concomitant T (HR 1.25, 95%CI 1.07-1.45) and patients with node negative (HR 1.12, 95% 0.93-1.35) or positive (HR 1.16, 95%CI 0.99-1.36) disease. Conclusions: Within the limitations of the available data and the different non-inferiority margins used in randomized trials, a shorter duration of adjuvant T is non-inferior to one year of therapy for DFS in patients with HER2 positive breast cancer, particularly in patients with ER positive disease. Further trials with appropriately chosen non-inferiority margins are needed to confirm the optimal duration of T in patients with low-risk disease.

scholarly journals Immunotherapy Implication of Signature-Guided Biomarker Discovery for Trastuzumab-Resistant HER2-Positive Breast Cancer

2020 ◽  
Author(s):  
Andrea Sand ◽  
Aspen T. Duffin ◽  
Geoffrey T. Riddell ◽  
Mitchel Piacsek ◽  
Brittany Last ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Biomarker Discovery ◽  
Early Stage ◽  
Cytotoxic T Cell ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Early Stage Disease ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

AbstractDespite the great improvement of patient outcomes by trastuzumab, a monoclonal antibody targeted on HER2-positive breast cancer, approximately 23% of patients with early-stage disease treated with adjuvant trastuzumab either fail to respond or experience recurrence within 10 years, highlighting the importance of identifying which HER2-positive patients would benefit from trastuzumab upfront. Efforts to identify biomarkers predictive of response to trastuzumab in initial breast tumor core biopsies have been complicated by the clinical and biological heterogeneity of HER2-positive tumors. Therefore, we identified a trastuzumab-resistant (TrR) signature that accurately predicts response to trastuzumab quantitively and qualitatively in vitro and in vivo, via repurposing transcriptome profiles in an engineered cell line model. We additionally demonstrated that our TrR signature was associated with tumor progression and capable of stratifying patient prognosis. Our study further illustrated the possible mechanism of this resistance as being less inherited cytotoxic T cell infiltration and failure to secrete Interferon-γ upon trastuzumab treatment in TrR tumors. These findings highlight the potential clinical application of TrR signature in treatment management and identifying possible immunotherapy interventions.

scholarly journals Real-world evidence from a University Hospital system regarding the uptake of adjuvant pertuzumab and/or neratinib before and after their FDA approval

2021 ◽  
Author(s):  
Ericson Stoen ◽  
Jodi Kagihara ◽  
Elena Shagisultanova ◽  
Christine M. Fisher ◽  
Andrew Nicklawsky ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Effects ◽  
Early Stage ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Node Positive ◽  
Her2 Positive Breast Cancer ◽  
Fda Approval ◽  
Node Positive Disease ◽  
Positive Breast Cancer

Abstract Purpose Adjuvant pertuzumab and neratinib are independently FDA-approved for treatment of early-stage HER2-positive breast cancer in combination with or following trastuzumab for one year, respectively. Both agents reduce the risk of recurrence; however, the absolute benefit is modest for many patients with added risk of adverse effects. The purpose of this study was to evaluate the clinical use of adjuvant pertuzumab and neratinib in patients with early-stage HER2-positive breast cancer. Methods Patients diagnosed with stage I–III HER2-positive breast cancer treated with trastuzumab at four University of Colorado Health hospitals between July 2016 and April 2019 were identified. Patient demographics, cancer stage, treatment, and administration of pertuzumab and/or neratinib were obtained. Results We identified a total of 350 patients who received adjuvant trastuzumab for stage I–III HER2-positive breast cancer; 253 (73.1%) had tumors that were ≥ T2 or node-positive disease. The rate of adjuvant pertuzumab use increased following FDA approval; pertuzumab was administered to the majority of patients with node-positive HER2-positive breast cancer. The use of adjuvant pertuzumab was associated with younger age, premenopausal status, and node-positive disease. Rates of administration of adjuvant neratinib were lower, with only 15.2% of patients receiving this therapy within 3 months of completing adjuvant trastuzumab. Conclusion In our cohort of patients treated within a diverse healthcare network, the majority of patients with node-positive HER2-positive breast cancer received adjuvant pertuzumab following FDA approval. The use of adjuvant neratinib was less common, potentially as a result of adverse effects, prolongation of therapy, previous administration of adjuvant pertuzumab, and modest benefit.

scholarly journals Influence of Ile655Val polymorphism on trastuzumab-induced cardiotoxicity in early-stage HER2 positive breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ljubica Vazdar ◽  
Ivo Darko Gabrić ◽  
Ivan Kruljac ◽  
Hrvoje Pintarić ◽  
Robert Šeparović ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Genotype Distribution ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Ventricular Ejection Fraction ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

AbstractTrastuzumab has improved the prognosis of HER2 positive breast cancer, but cardiotoxicity remains a concern. We aimed to identify risk factors for trastuzumab-induced cardiotoxicity, with an emphasis on the HER2 Ile655Val single nucleotide polymorphism. This single-center case–control study included 1056 patients with early-stage HER2 positive breast cancer that received adjuvant trastuzumab. Cardiotoxicity was defined as a decline in left ventricular ejection fraction (LVEF) > 15% in patients without previous cardiomyopathy, or > 10% in patients with baseline LVEF of < 50%. Patient characteristics and cardiac parameters were compared in 78 (7.38%) cases and 99 randomly assigned controls, and the polymorphism was genotyped using real-time polymerase chain reaction. Cardiotoxicity was independently associated with advanced age (P = 0.024), lower body mass index (P = 0.023), left breast involvement (P = 0.001), N3 status (P = 0.004), diabetes (P = 0.016), and a family history of coronary artery disease (P = 0.019). Genotype distribution was as follows: A/A (Ile/Ile) was found in 111 (62.7%) patients, A/G (Ile/Val) in 60 (33.9%) patients, and G/G (Val/Val) in 6 (3.4%) patients. The genotype was not associated with cardiotoxicity or the severity of heart failure, reversibility, and recovery time. We found no association between the HER2 Ile655Val polymorphism and trastuzumab-induced cardiotoxicity; therefore, we do not recommend routine cardiotoxicity-risk stratification using this polymorphism.

Sign in / Sign up

Export Citation Format

Share Document