Heregulin-induced cell migration is prevented by trastuzumab and trastuzumab-emtansine in HER2+ breast cancer

2021 ◽  
Author(s):  
Joselina Magali Mondaca ◽  
Ana Carla Castro Guijarro ◽  
Marina Inés Flamini ◽  
Angel Matias Sanchez
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Trastuzumab Emtansine ◽  
Her2 Breast Cancer

scholarly journals Current trends in the treatment of HR+/HER2+ breast cancer

2021 ◽  
Vol 17 (13) ◽  
pp. 1665-1681
Author(s):  
Charlene Kay ◽  
Carlos Martínez-Pérez ◽  
James Meehan ◽  
Mark Gray ◽  
Victoria Webber ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Trastuzumab Emtansine ◽  
Breast Cancers ◽  
Newly Diagnosed ◽  
Luminal A ◽  
New Agents ◽  
Her2 Breast Cancer ◽  
Current Trends

Treatment for HR+/HER2+ patients has been debated, as some tumors within this luminal HER2+ subtype behave like luminal A cancers, whereas others behave like non-luminal HER2+ breast cancers. Recent research and clinical trials have revealed that a combination of hormone and targeted anti-HER2 approaches without chemotherapy provides long-term disease control for at least some HR+/HER2+ patients. Novel anti-HER2 therapies, including neratinib and trastuzumab emtansine, and new agents that are effective in HR+ cancers, including the next generation of oral selective estrogen receptor downregulators/degraders and CDK4/6 inhibitors such as palbociclib, are now being evaluated in combination. This review discusses current trials and results from previous studies that will provide the basis for current recommendations on how to treat newly diagnosed patients with HR+/HER2+ disease.

The role of ado-trastuzumab emtansine in current clinical practice

2020 ◽  
pp. 107815522095186
Author(s):  
Alla Turshudzhyan
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Therapy ◽  
Early Breast Cancer ◽  
Bystander Effect ◽  
Residual Disease ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
Post Surgery ◽  
Her2 Breast Cancer ◽  
Randomized Controlled Studies

Objective This review reflects the literature from 2019 to 2020 on ado-trastuzumab emtansine’s (T-DM1) therapeutic use, clinical controversies, and newest perspectives on use. Data sources: PubMed was used as a database. Search “ado-trastuzumab emtansine” on June 11th, 2020 resulted in 57 publications: 20 clinical trials, two metanalysis, six randomized controlled studies, 13 reviews, and two systematic reviews. Of the 57 publications, 34 were descriptive of the topic in question and were used for this review. Data summary: T-DM1 is now used for patients with HER2 breast cancer who have residual disease post surgery after neoadjuvant chemotherapy (KATHERINE trial). Initial success prompted KRISTINE trial, which investigated whether T-DM1 can be used as a neoadjuvant therapy. While it did have fewer adverse events, T-DM1 was inferior to chemotherapy in treating early breast cancer. Noted shortcomings of the drug were toxicity limited Cmax, slow rate of internalization, lack of payload bystander effects, and number of resistance mechanisms. Proposed solutions were pre-treatment with metformin to augment drug internalization by the cell, use of second generation anti-HER2 antibody-drug conjugates to overcome developing resistance, payload swapping to increase bystander effect. Conclusions While T-DM1 has fewer side-effects, it is inferior to chemotherapy in early breast cancer treatment. More research should be done to overcome resistance pathways, identify rate-limiting intracellular processing pathways, improve bystander, and enhance internalization of the drug. Until more research is done, T-DM1 will continue to be used in HER2 positive breast cancer as well as a few other HER2 expressing tumors that fail to respond to neoadjuvant therapy.

scholarly journals Neoadjuvant T-DM1/pertuzumab and paclitaxel/trastuzumab/pertuzumab for HER2+ breast cancer in the adaptively randomized I-SPY2 trial

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Amy S. Clark ◽  
Christina Yau ◽  
Denise M. Wolf ◽  
Emanuel F. Petricoin ◽  
Laura J. van ‘t Veer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Clinical Stage ◽  
Cytotoxic Chemotherapy ◽  
Trastuzumab Emtansine ◽  
Phase 2 ◽  
Excellent Outcome ◽  
Her2 Breast Cancer ◽  
Biopsy Specimens ◽  
Common Control

AbstractHER2-targeted therapy dramatically improves outcomes in early breast cancer. Here we report the results of two HER2-targeted combinations in the neoadjuvant I-SPY2 phase 2 adaptive platform trial for early breast cancer at high risk of recurrence: ado-trastuzumab emtansine plus pertuzumab (T-DM1/P) and paclitaxel, trastuzumab and pertuzumab (THP). Eligible women have >2.5 cm clinical stage II/III HER2+ breast cancer, adaptively randomized to T-DM1/P, THP, or a common control arm of paclitaxel/trastuzumab (TH), followed by doxorubicin/cyclophosphamide, then surgery. Both T-DM1/P and THP arms ‘graduate’ in all subtypes: predicted pCR rates are 63%, 72% and 33% for T-DM1/P (n = 52), THP (n = 45) and TH (n = 31) respectively. Toxicity burden is similar between arms. Degree of HER2 pathway signaling and phosphorylation in pretreatment biopsy specimens are associated with response to both T-DM1/P and THP and can further identify highly responsive HER2+ tumors to HER2-directed therapy. This may help identify patients who can safely de-escalate cytotoxic chemotherapy without compromising excellent outcome.

Trastuzumab emtansine (T-DM1) renders HER2 + breast cancer highly susceptible to CTLA-4/PD-1 blockade

2015 ◽  
Vol 7 (315) ◽  
pp. 315ra188-315ra188 ◽  
Author(s):  
Philipp Müller ◽  
Matthias Kreuzaler ◽  
Tarik Khan ◽  
Daniela S. Thommen ◽  
Kea Martin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Trastuzumab Emtansine ◽  
Her2 Breast Cancer

scholarly journals NCOG-09. EFFICACY OF HER2-TARGETED ANTIBODY THERAPY IN HER2-POSITIVE BREAST CANCER BRAIN METASTASES: A NATIONAL ANALYSIS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii131-ii131
Author(s):  
Alexander Hulsbergen ◽  
Marike Broekman ◽  
Timothy Smith ◽  
Ayal A Aizer ◽  
Bryan Iorgulescu
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Brain Metastases ◽  
Antibody Therapy ◽  
National Study ◽  
Trastuzumab Emtansine ◽  
Landmark Analysis ◽  
Her2 Breast Cancer ◽  
Breast Cancer Brain Metastases ◽  
National Analysis

Abstract BACKGROUND Breast cancer brain metastases (BCBM) commonly develop in human epidermal growth factor 2-positive (HER2+) breast cancer, but BCBM patients are underrepresented in clinical trials, leading to a lack of knowledge on the efficacy of HER2-targeted therapy in this population. METHODS We analyzed clinical characteristics and outcomes of HER2+BCBM patients from the National Cancer Database 2010–2016, comprising 70% of newly-diagnosed cancers in the U.S, to assess overall survival (OS) associated with HER2-targeted monoclonal antibody therapy (HER2-mab; i.e. trastuzumab, pertuzumab, and trastuzumab emtansine; encoded as of 2013). Survival was estimated with Kaplan-Meier techniques and compared with landmark analysis and Cox regression. The landmark timepoint was selected at which 75% of HER2-mab patients received HER2-mab, which was within 58 days of diagnosis. RESULTS 1,059 HER2+BCBM patients were identified, 717 (67.7%) patients were estrogen receptor negative (ER-) and 342 (32.3%) were ER+. Median follow-up was 12.0 months, at the end of which 73.8% of patients were deceased. Median OS was 12.2 and 22.1 months for ER- and ER+ patients, respectively. Following FDA approvals of pertuzumab (2012) and ado-trastuzumab emtansine (2013), HER2-mab usage for HER2+BCBM patients rose from 53.6% in 2013 to 71.7% in 2016. 420 BCBM patients had complete data for landmark analyses: 70.0% (n=294) received HER2-mab and 30.0% (n=126) did not, in which HER2-mab was associated with significantly improved OS in both ER- (median 22.2 months, 95%CI: 18.2-25.4; vs. 9.5 mos, 95%CI: 6.3-10.7; p=0.0001) and ER+ (median 25.7 months, 95%CI: 21.4-not reached; vs. 19.6 months, 95%CI: 11.1-35.2; p=0.02) patients. In multivariable Cox landmark analysis adjusted for ER status, age at diagnosis, extracranial disease, chemotherapy, radiotherapy, and metastasectomy; HER2-mab demonstrated significantly improved OS (hazard ratio 0.59 vs. no HER2-mab, 95%CI: 0.44-0.77; p< 0.001). CONCLUSIONS In this large national study, HER2-mab was associated with substantially improved overall survival in HER2+ BCBM patients.

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