Alle Vortragsfolien


[GS6-01] Oral Paclitaxel with Encequidar: The first orally administered paclitaxel shown to be superior to IV paclitaxel on confirmed response and survival with less neuropathy: a phase III clinical study in metastatic breast cancer



Umanzor G, Rugo H, Cutler DL, Barrios FJ, et al.




The authors conclude that: Oral paclitaxel + encequidar is the first orally administered paclitaxel shown to be superior to IV paclitaxel for confirmed response, progression-free survival, and overall survival, with minimal clinically meaningful neuropathy.




[GS6-02] Apobec and BRCA mutation signatures are mutually exclusive in breast cancer



Harris RS, Smid M, Wilting S, Roelofs P, et al.




The authors conclude that: While the AGEING mutational process occurs independent of either the APOBEC or BRCA mutational processes, the APOBEC and BRCA signatures occur in a mutually exclusive manner. However, cell lines are able to support both mutation processes simultaneously, indicating there is no synthetic lethal interaction. These results suggest a model in which dominant mutational processes such as APOBEC and BRCA, once activated, provide sufficient mutational fuel for tumor evolution such that activation of an additional dominant mutation process is not necessary. Our results also highlight the need to develop distinct approaches to diagnose and treat breast tumors with these different mutational processes.




[GS6-03] Cisplatin versus doxorubicin/cyclophosphamide as neoadjuvant treatment ingermline BRCA mutation carriers (BRCA carriers) with HER2-negative breast cancer:Results from the INFORM trial (TBCRC 031)



Tung N, Arun B, Hofstatter E, Hacker MR, et al.




The authors conclude that: While CDDP has single-agent activity in BRCA carriers with HER2-negative breast cancer, the pCR rate with CDDP is not higher than with standard AC chemotherapy. CDDP activity was notably lower in BRCA carriers with hormone-receptor positive breast cancer, though the sample size was small. Study-collected tumor and blood samples are being analyzed for biomarkers of response.




[GS6-04] Co-occurring gain-of-function mutations in HER2 and HER3 modulate HER2/HER3 activation, breast cancer progression, and HER2 inhibitor sensitivity



Hanker AB, Sekar Jayanthan H, Ye D, Lin C, et al.




The authors conclude that: Co-expression of mutant HER2 and mutant HER3 promotes ligand-independent HER2/HER association, HER3 phosphorylation, and cancer cell invasion via enhanced activation of the PI3K pathway; this enhanced signaling output is incompletely blocked by neratinib. Therefore, breast cancers expressing co-occurring HER2 and HER3 mutations may require the addition of a PI3Kα inhibitor to a HER2 TKI.




[GS6-05] A joint atlas of single-cell and bulk RNA-seq in metastatic breast cancer allows inference of oncogenic and drug-resistant transcriptional programs in malignant cells and the tumor microenvironment



Cohen O, Abravanel D, Slyper M, Klughammer J, et al.




The authors conclude that: To the best of our knowledge these data represent the first integration of single cell and bulk RNA-seq data in MBC, resulting in a comprehensive single-cell-resolution transcriptional atlas, and a catalog of drug-resistance oncogenic progs with implications for immunotherapy and precision-oncology.




[GS6-06] A neoadjuvant trial with letrozole identifies PRR11 in the 17q23 amplicon as a mechanism of resistance to endocrine therapy in ER-positive breast cancer

Lee K, Guerrero-Zotano A, Hanker A, Servetto A, et al.


The authors conclude that: These data suggest that 1) PRR11 is a mediator of resistance to antiestrogens via amplification of PI3K/AKT signaling, and 2) PI3Kα is a potential therapeutic target in ER+ BCs harboring PRR11 amplification.




[GS6-07] Discussant



Adrian V. Lee, PhD
University of Pittsburgh
Hillman Cancer Center
Pittsburgh, PA



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