Efficacy and Tolerability of Lapatinib in the Management of Breast Cancer

Approximately 20%–25% of all breast cancers over express a key cell surface growth factor receptor known as HER2. HER2 plays a key role in cell growth and proliferation and is linked to worse clinical outcomes, making it a logical therapeutic target. The first HER2 targeted drug to be approved by the FDA, was the humanized monoclonal antibody trastuzumab, after it showed improvements in survival in the adjuvant setting, and delayed time to progression in the metastatic setting. Although highly effective, for reasons that are not clear, some patients display resistance to trastuzumab. Lapatinib is an oral, small molecule tyrosine kinase inhibitor, that inhibits both the HER1 ahd HER2 receptors and may be able to overcome trastuzumab resistance. Lapatinib is approved in the second line setting for use in combination with capecitabine or with letrozole. In this review, we will discuss the indications, concerns or any issues with regards to the drug

Improving survival and limiting toxicity: latest advances in treating human epidermal growth factor receptor 2 overexpressing breast cancer

In recent years, new strategies for the treatment of breast cancer have focused on extensive target identification and understanding the expression, regulation and function of critical signaling pathways involved in breast cancer initiation and progression. This has led to significant progress in developing and understanding human epidermal growth factor receptor 2 (HER2)-targeted therapies, which in turn, has translated into significant increases in median survival for patients with HER2-overexpressing breast cancer. It is becoming increasingly difficult to make specific recommendations for the optimal treatment of HER2-overexpressing breast cancer since the field is evolving so rapidly. However, despite the many randomized trials that have been undertaken showing improvement in survival, the current standard treatment for HER2-overexpressing breast cancer continues to revolve around the addition of chemotherapy to a HER2-targeted agent, which in turn, carries substantial toxicities. This article reviews agents that have recently been investigated to treat HER2-overexpressing breast cancers. The goal is ultimately to increase the magnitude and duration of response to trastuzumab-based treatment while minimizing toxicity. Studies addressing length of therapy duration, the superiority and side-effect profile of the different biological drug combinations, and determination of biomarkers of resistance to HER2 therapy will be instrumental in decreasing morbidity and mortality for patients with HER2-overexpressing breast cancer

Microwave characterization of high-temperature superconductors

Thick (10-15 {mu}m) Tl-Ba-Ca-Cu-O films have been deposited onto yttria-stabilized zirconia and Ag substrates by d.c. magnetron sputtering techniques. Direct deposition onto 1'' diameter yttria-stabilized zirconia yields films with typical 22 GHz surface resistance (R{sub s}) values of 5.2 {plus minus} 2 m{Omega} and 52 {plus minus} 2 m{Omega} at 10 K and 77 K, respectively. For comparison, R{sub s} of Cu at this same frequency is 10 m{Omega} at 4 K and 22 m{Omega} at 77 K. Tl-Ba-Ca-Cu-O films have also been deposited onto 1'' diameter Ag substrates using Au/Cu, Cu, and BaF{sub 2} buffer layers. The lowest R{sub s} values were obtained on films with a BaF{sub 2} buffer layer, typical values being 7.8 {plus minus} 2 m{Omega} and 30.6 {plus minus} 2 m{Omega} (measured at 22 GHz) at 10 K and 77 K, respectively. Larger films (1.5'' diameter) with similar R{sub s} values were prepared using this same technique, demonstrating that the fabrication process can be scaled to larger surface areas. These films are promising for radiofrequency cavity applications because they are thick (50-75 times the London penetration depth), have relatively large surface areas, are fabricated on metallic substrates, and have R{sub s} values that are competitive with Cu at 77 K and are lower than Cu at 4 K. Because they are polycrystalline and unoriented, it is anticipated that their R{sub s} values can be lowered by improving the processing technique. High-quality films of YBa{sub 2}Cu{sub 3}O{sub 7} have been electron-beam deposited onto 1'' LaGaO{sub 3} and 1.5'' LaAlO{sub 3} substrates. The 1'' sample is characterized by R{sub s} values of 0.2 {plus minus} 0.1 m{Omega} at 4 K and 18.6 {plus minus} 2 m{Omega} at 77 K. The 4-K value is only 2-4 times higher than Nb. The 1.5'' sample has R{sub s} values (measured at 18 GHz) of 0.93 {plus minus} 2 m{Omega} and 71 {plus minus} 3 m{Omega} at 10 K and 77 K, respectively. 18 refs., 8 figs