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Abstract Recent trials have shown the efficacy of trastuzumab deruxtecan (T-DXd) in HER2-negative patients, but there is not yet a way to identify which patients will best respond, especially with the inability of current HER2 IHC and FISH assays to accurately determine HER2 expression in the unamplified setting. Here, we present a heavily pre-treated patient with triple-negative breast cancer (HER2 IHC 0 who had a complete response to T-DXd. In this case, we used a CLIA-certified reverse-phase protein array-based proteomic assay (RPPA) to determine that the patient had moderate HER2 protein expression (HER2Total 2+, 42%) and activation (HER2Y1248 1+, 23%). Using these results, we determined that the patient may benefit from T-Dxd despite being traditionally qualified as HER2 IHC 0. These findings highlight the potential for proteomics-based assays that may more accurately quantitate HER2 and (its activation) in the HER2 unamplified/IHC 0 setting to better select patients whose tumors are classically molecularly defined as HER2 IHC 0, but still could respond to HER2-directed therapy, and give patients access to therapies which for which they otherwise would not be eligible.

In 1998, the government of Ecuador enacted a special law with the goal of both promoting environmental preservation and economic development in the Galapagos Islands. The reforms in the Special Law of 1998 were sweeping. Among other things it created the Galapagos Marine Preserve, limited the ability of immigrants arriving from mainland Ecuador to secure employment, restricted fishing to local residents only, and increased the institutional power of regulatory organisations like the Galapagos National Park. This article presents the results of a series of qualitative interviews conducted in July 2011 with local Island leaders on their support for the Special Law of 1998 in general and in regards to its implementation. The interviews also asked the respondents' opinions on a wider set of ecotourism policies and issues. The findings indicate that generally there is a great amount of support for the law amongst leaders, but there is a strong consensus that the Special Law has not been implemented effectively. The reasons behind these failures of implementation are multifaceted, but include: the weak and fragmented status of Galapagos institutions, a lack of professionalised leadership, leadership which engages in politicised decision-making, and, finally, failures to enforce unpopular provisions of the Special Law. [ABSTRACT FROM AUTHOR]