Models that recapitulate the complexity of human tumors are urgently needed to develop more effective cancer therapies. We report a bank of human patient-derived xenografts (PDXs) and matched organoid cultures from tumors that represent the greatest unmet need: endocrine-resistant, treatment-refractory and metastatic breast cancers. We leverage matched PDXs and PDX-derived organoids (PDxO) for drug screening that is feasible and cost-effective with in vivo validation. Moreover, we demonstrate the feasibility of using these models for precision oncology in real time with clinical care in a case of triple-negative breast cancer (TNBC) with early metastatic recurrence. Our results uncovered a Food and Drug Administration (FDA)-approved drug with high efficacy against the models. Treatment with this therapy resulted in a complete response for the individual and a progression-free survival (PFS) period more than three times longer than their previous therapies. This work provides valuable methods and resources for functional precision medicine and drug development for human breast cancer.

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Background Research indicates that dispositional mindfulness is associated with positive psychological functioning. Although this disposition has been linked with beneficial outcomes in the broader mental health literature, less is known about dispositional mindfulness in cancer survivors and how it may be linked with indices of psychological and physical health relevant to cancer survivorship. Methods We conducted a multivariate path analysis of data from a heterogeneous sample of cancer patients (N = 97) to test the Mindfulness-to-Meaning Theory, an extended process model of emotion regulation linking dispositional mindfulness with cancer-related quality of life via positive psychological processes. Results We found that patients endorsing higher levels of dispositional mindfulness were more likely to pay attention to positive experiences (β = .56), a tendency which was associated with positive reappraisal of stressful life events (β = .51). Patients who engaged in more frequent positive reappraisal had a greater sense of meaning in life (β = .43) and tended to savor rewarding or life affirming events (β = .50). In turn, those who engaged in high levels of savoring had better quality of life (β = .33) and suffered less from emotional distress (β = −.54). Conclusions Findings provide support for the Mindfulness-to-Meaning Theory, and help explicate the processes by which mindfulness promotes psychological flourishing in the face of cancer.