Supplementary Material for: Functional precision medicine successfully guides therapeutic regimen of ‘cancer of unknown primary’ later classified as triple-negative breast cancer – a case report

Introduction: Controlled randomized trials, molecular analytics and guideline recommendations have so far been irreplaceable tools to ensure appropriate treatment and decision making for physicians and patients. Individual patient models are increasingly complementing these methods, particularly in the case of advanced cancers, rare cancers and cancers of unknown primary, as in these cases comprehensive clinical evidence is unavailable, often resulting in poor treatment success, even after stratification. Case Presentation: Here we report a 53-year-old patient with CUP with axillary lymph node metastases for whom patient-derived 3D (PD3D®) tumor organoids successfully guided personalized treatment. PD3D tumor models were used to screen drugs that are effective in the suspected primary tumor site. The screen revealed sensitivity to doxorubicin, which is not indicated for CUP treatment, but hinted towards breast cancer that was subsequently confirmed as TNBC. The patient showed partial remission to first-line doxorubicin and cyclophosphamide, which was followed by docetaxel. Subsequent radiotherapy eventually led to a complete remission, which is still ongoing. Conclusion: We conclude that pre-therapeutic drug sensitivity screening with PD3D tumor organoids can be essential in guiding and enabling an effective personalized treatment for patients with hard-to-treat cancers, like CUP or TNBC.