The change of paradigm in the treatment of HER2-positive breast cancer with the development of new generation antibody-drug conjugates
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In this article , the authors developed a new antibody-drug conjugate, trastuzumab emtansine, which is a potent cytotoxic agent bound to trastusumab and is currently a standard therapeutic strategy for HER2-positive metastatic breast cancer.Abstract:
HER2-positive breast cancer is an aggressive disease. As a result of the development of specific HER2-targeted therapies, such as trastuzumab, more than 20 years ago, the prognosis of these patients has improved. Metastatic HER2-positive breast cancer patients are achieving better survival rates upon treatment with anti-HER2 therapies than patients with HER2-negative disease. Double HER2 blockade with trastuzumab and pertuzumab combined with a taxane achieved an unprecedented survival of over 57 months in first-line patients. Trastuzumab emtansine, the first antibody-drug conjugate approved for patients in second-line treatment was a potent cytotoxic agent bound to trastuzumab and is currently a standard therapeutic strategy. Despite the progress in treatment development, most patients develop resistance and eventually relapse. Advances in the design of antibody-drug conjugates have led to the development of new generation drugs with enhanced properties, such as trastuzumab deruxtecan and trastuzumab duocarmazine, which are significantly changing the paradigm in the treatment of HER2-positive metastatic breast cancer.read more
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Advances in Targeted Therapy of Breast Cancer with Antibody-Drug Conjugate
TL;DR: In this article , the development of ADC-based targeted breast cancer therapy and the clinical translation of ADC drugs for breast cancer treatment are discussed, and a review of the development and clinical translation for ADC drugs is presented.
References
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Journal ArticleDOI
Use of Chemotherapy plus a Monoclonal Antibody against HER2 for Metastatic Breast Cancer That Overexpresses HER2
Dennis J. Slamon,Brian Leyland-Jones,Steven Shak,Hank Fuchs,Virginia E. Paton,Alex Bajamonde,Thomas Fleming,Wolfgang Eiermann,Janet M. Wolter,Mark D. Pegram,José Baselga,Larry Norton +11 more
TL;DR: The addition of trastuzumab to chemotherapy was associated with a longer time to disease progression, a higher rate of objective response, a longer duration of response, and a lower rate of death at 1 year.
Journal ArticleDOI
Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer
Sunil Verma,David Miles,Luca Gianni,Ian E. Krop,Manfred Welslau,José Baselga,Mark D. Pegram,Do Youn Oh,Véronique Diéras,Ellie Guardino,Liang Fang,M. Lu,Steven R. Olsen,K. L. Blackwell +13 more
TL;DR: T-DM1 significantly prolonged progression-free and overall survival with less toxicity than lapatinib plus capecitabine in patients with HER2-positive advanced breast cancer previously treated with trastuzumab and a taxane.
Journal ArticleDOI
Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer
Gunter von Minckwitz,Chiun Sheng Huang,Max S. Mano,Sibylle Loibl,Eleftherios P. Mamounas,Michael Untch,Norman Wolmark,P Rastogi,Andreas Schneeweiss,Andrés Redondo,Hans Holger Fischer,William Jacot,Alison Conlin,Claudia Arce-Salinas,Irene Wapnir,Christian Jackisch,Michael P. DiGiovanna,Peter A. Fasching,John Crown,Pia Wülfing,Zhimin Shao,Elena Rota Caremoli,Haiyan Wu,Lisa H. Lam,David Tesarowski,Melanie C. Smitt,Hannah Douthwaite,Stina M. Singel,Charles E. Geyer +28 more
TL;DR: Among patients with HER2‐positive early breast cancer who had residual invasive disease after completion of neoadjuvant therapy, the risk of recurrence of invasive breast cancer or death was 50% lower with adjuvant T‐DM1 than with trastuzumab alone.
Journal ArticleDOI
Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer
Shanu Modi,Cristina Saura,Toshinari Yamashita,Yeonhee Park,Sung Bae Kim,Kenji Tamura,Fabrice Andre,Hiroji Iwata,Yoshinori Ito,Junji Tsurutani,Junji Tsurutani,Joohyuk Sohn,Neelima Denduluri,Christophe Perrin,Kenjiro Aogi,Eriko Tokunaga,Seock-Ah Im,Keun Seok Lee,Sara A. Hurvitz,Javier Cortes,Caleb Lee,Shuquan Chen,Lin Zhang,Javad Shahidi,Antoine Yver,Ian E. Krop +25 more
TL;DR: Tastuzumab deruxtecan showed durable antitumor activity in a pretreated patient population with HER2-positive metastatic breast cancer and requires attention to pulmonary symptoms and careful monitoring.
Journal ArticleDOI
Trastuzumab Plus Adjuvant Chemotherapy for Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Planned Joint Analysis of Overall Survival From NSABP B-31 and NCCTG N9831
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TL;DR: The addition of trastuzumab to paclitaxel after doxorubicin and cyclophosphamide in early-stage HER2-positive breast cancer results in a substantial and durable improvement in survival as a result of a sustained marked reduction in cancer recurrence.
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