Journal ArticleDOI
Beyond Trastuzumab and Lapatinib: New Options for HER2-Positive Breast Cancer
Dimitrios Zardavas,David Cameron,Ian E. Krop,Martine Piccart +3 more
- Vol. 33, Iss: 33, pp 2-11
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TLDR
The clinical data of the HER2-targeted agents under development are presented, as well as an overview of the biologic rationale for the development of agents aimed at circumventing anti-HER2 resistance.Abstract:
HER2-positive breast cancer (BC) constitutes a molecular subtype of the disease with an aggressive biologic behavior. Trastuzumab revolutionized the treatment of this disease, changing its natural history. Lapatinib is active in the metastatic setting, approved for patients who were pretreated with trastuzumab. However, resistance to anti-HER2 agents is a major clinical issue, occurring in both early-stage and advanced disease, and new treatment options are clearly needed. An abundance of HER2-targeted agents are being clinically developed: monoclonal antibodies, small molecule inhibitors, and antibody drug conjugates (ADC). Combining HER2-targeted agents in regimens of dual HER2 blockade has already reached clinical practice in the metastatic setting, confirming the preclinical efficacy of enhanced HER2 inhibition. Promising results have been generated in the neoadjuvant setting, and large randomized trials are seeking evidence for dual HER2 blockade in the adjuvant setting. ADC represent another hope for improved treatment outcomes of HER2-positive BC, as exemplified by the positive results of clinical trials employing trastuzumab-DM1 (trastuzumab emtansine, T-DM1). Moreover, an understanding of the molecular mechanisms mediating resistance to HER2 blockade has opened new therapeutic avenues, with several targeted agents entering clinical trials. This paper presents the clinical data of the HER2-targeted agents under development, as well as an overview of the biologic rationale for the development of agents aimed at circumventing anti-HER2 resistance.read more
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Journal ArticleDOI
A natural antisense lncRNA controls breast cancer progression by promoting tumor suppressor gene mRNA stability.
Mahdieh Jadaliha,Omid Gholamalamdari,Wei Tang,Yang Zhang,Ana Petracovici,Qinyu Hao,Aamira Tariq,Tae Gyoon Kim,Sarah E. Holton,Deepak Singh,Xiaoling Li,Susan M. Freier,Stefan Ambs,Rohit Bhargava,Ashish Lal,Supriya G. Prasanth,Jian Ma,Jian Ma,Kannanganattu V. Prasanth +18 more
TL;DR: Key roles played by NAT lncRNAs in regulating post-transcriptional gene expression of key oncogenic or tumor suppressor genes, thereby contributing to TNBC progression are demonstrated.
Journal ArticleDOI
Efficacy of Adjuvant Trastuzumab for Patients With Human Epidermal Growth Factor Receptor 2–Positive Early Breast Cancer and Tumors ≤ 2 cm: A Meta-Analysis of the Randomized Trastuzumab Trials
Ciara C. O’Sullivan,Ian Bradbury,Christine Campbell,Marc Spielmann,Edith A. Perez,Heikki Joensuu,Joseph P. Costantino,Suzette Delaloge,Priya Rastogi,Dimitrios Zardavas,Karla V. Ballman,Eileen Holmes,Evandro de Azambuja,Martine Piccart-Gebhart,Jo Anne Zujewski,Richard D. Gelber +15 more
TL;DR: Women with small (≤ 2 cm) human epidermal growth factor receptor 2 (HER2) -positive breast cancer treated in randomized trastuzumab trials derived substantial DFS and OS benefit from adjuvant trastzumab.
Journal ArticleDOI
The past and future of breast cancer treatment-from the papyrus to individualised treatment approaches.
TL;DR: How breast cancer treatment has improved since the earliest descriptions, in ancient times, and how future approaches, such as gene signatures, molecular profiling, and liquid biopsies, aim to further develop individualised treatments and improve treatment outcomes are reviewed.
Journal ArticleDOI
Novel Hsp90 inhibitor FW-04-806 displays potent antitumor effects in HER2-positive breast cancer cells as a single agent or in combination with lapatinib.
TL;DR: The combination of FW-04-806 and lapatinib showed synergistic reduction of HER2 expression and the downstream PI3K/Akt and Ras/MEK/ERK pathways, enhanced suppression of Akt-mediated FOXO3a inactivation and augmented antitumor efficacy on SKBR3 xenografts with a favorable toxicity profile, suggesting its viability as a combination therapy for clinical studies in HER2+ breast cancer patients.
Journal ArticleDOI
A phase I/II trial of the safety and clinical activity of a HER2-protein based immunotherapeutic for treating women with HER2-positive metastatic breast cancer
Giuseppe Curigliano,Gilles Romieu,Mario Campone,Thierry Dorval,Lionel Duck,Jean-Luc Canon,C. Roemer-Becuwe,Mario Roselli,Silvia P. Neciosup,Wivine Burny,Andrea Callegaro,Pedro Miguel De Sousa Alves,Jamila Louahed,Vincent Brichard,Fr�d�ric F. Lehmann +14 more
TL;DR: In this paper, the authors evaluated the safety and clinical activity of a cancer immunotherapeutic agent (recombinant HER2 protein (dHER2) and the immunostimulant AS15) in patients with metastatic breast cancer (MBC).
References
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Journal ArticleDOI
Pertuzumab plus Trastuzumab plus Docetaxel for Metastatic Breast Cancer
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