Individual xenografts for personalized treatment of women with metastatic triple negative breast cancer

Abstract

Aim: Triple negative breast cancer (TNBC) is the most severe subtype of breast cancer with poor prognosis even when treated at a localized stage. The treatment of metastatic TNBC is still challenging daily clinical practice, mainly because of the lack of targeted therapies. In the last years, a molecular sub-classification of TNBC has opened the way to personalized medicine for this type of severe cancer.

Methods: In this study, we assessed the added value of combining molecular analyses with individual xenografts to personalize the treatment of resort for five women with metastatic TNBC. While a patient was receiving one or two lines of chemotherapy, the corresponding xenograft model was tested with different drugs or drug combinations, mainly based on transcriptomic analyses of the tumor and on theoretical activated canonical pathways.

Results: On the basis of transcriptomic analyses and chemosensitivity data obtained from TNBC individual xenografts, we personalized the resort treatment for the five women in our study. In all cases, despite the fact that this resort treatment was a third-line or a fourth-line treatment, the time to progression was longer than that observed with previous lines of chemotherapy. When we explored the 19 chemotherapy regimens given to these women and their corresponding xenograft models, there was a strong correlation between ΔSUV_max (maximum standard uptake value) on positron emission tomography-computed tomography and the corresponding coefficients of inhibition obtained in mice.

Conclusion: The combination of gene expression profiling and individual xenografts is a promising method and could be proposed as a personalized therapeutic resort for women with metastatic TNBCs.

Keywords

Patient-derived xenografts / triple negative metastatic breast cancer / personalized treatment

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