We have located links that may give you full text access.
JOURNAL ARTICLE
RESEARCH SUPPORT, N.I.H., EXTRAMURAL
RESEARCH SUPPORT, NON-U.S. GOV'T
RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
Acquired HER2 mutations in ER + metastatic breast cancer confer resistance to estrogen receptor-directed therapies.
Nature Genetics 2019 Februrary
Seventy percent of breast cancers express the estrogen receptor (ER), and agents that target the ER are the mainstay of treatment. However, virtually all people with ER+ breast cancer develop resistance to ER-directed agents in the metastatic setting. Beyond mutations in the ER itself, which occur in 25-30% of people treated with aromatase inhibitors1 -4 , knowledge about clinical resistance mechanisms remains incomplete. We identified activating HER2 mutations in metastatic biopsies from eight patients with ER+ metastatic breast cancer who had developed resistance to aromatase inhibitors, tamoxifen or fulvestrant. Examination of treatment-naive primary tumors in five patients showed no evidence of pre-existing mutations in four of five patients, suggesting that these mutations were acquired under the selective pressure of ER-directed therapy. The HER2 mutations and ER mutations were mutually exclusive, suggesting a distinct mechanism of acquired resistance to ER-directed therapies. In vitro analysis confirmed that the HER2 mutations conferred estrogen independence as well as-in contrast to ER mutations-resistance to tamoxifen, fulvestrant and the CDK4 and CDK6 inhibitor palbociclib. Resistance was overcome by combining ER-directed therapy with the irreversible HER2 kinase inhibitor neratinib.
Full text links
Trending Papers
A Personalized Approach to the Management of Congestion in Acute Heart Failure.Heart International 2023
Potential Mechanisms of the Protective Effects of the Cardiometabolic Drugs Type-2 Sodium-Glucose Transporter Inhibitors and Glucagon-like Peptide-1 Receptor Agonists in Heart Failure.International Journal of Molecular Sciences 2024 Februrary 21
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app