Organoids from Patient Biopsy Samples can Predict the Response of BC Patients to Neoadjuvant Chemotherapy

Abstract Background Neoadjuvant chemotherapy (NAC) has been widely used to treat locally advanced and inflammatory breast cancer. The initial purpose of neoadjuvant chemotherapy in operable breast cancer is to reduce the tumor stage, achieve local control, and increase the conservative operation rate. Another significant advantage of using neoadjuvant chemotherapy is the early identification of unresponsive tumors, predicting the sensitivity of new drugs and promoting the development of new medicines and clinical trials. It is generally believed that complete pathological response (pCR) after neoadjuvant chemotherapy treatment predicts survival. The overall survival rate of patients who achieve pCR is much higher than that of patients who do not. Therefore, it is essential to predict the response of patients to neoadjuvant chemotherapy. There is increasing evidence that patient-derived organoids (PDOs) can be used in cancer research and drug development and for the personalized in vitro evaluation of drug responses.Method We generated a living organoid biobank from locally advanced breast cancer patients receiving neoadjuvant chemotherapy. These patients had three clinically common molecular types of breast cancer (luminal-type, triple-negative and HER2+ breast cancer). When the patient received clinical neoadjuvant chemotherapy, the organoids were treated with similar drugs, thereby simulating the situation of the patient receiving treatmentResult We successfully constructed organoids from breast cancer biopsies to simulate clinical treatment, demonstrating that viable tumoroid lines can be generated from a small sample of tissue. The phenotype of breast cancer organoid often agreed with the original breast cancer according to the blinded histopathological analysis of H&E stain tissue and organoid sections. Our clinical trial data confirm that the patient's response to chemotherapy closely matches the organoids’ response to drugs. The patient-derived organoids may identify breast cancer patients who respond to neoadjuvant chemotherapy and thereby improve initial care.Conclusion Our data indicate that patient-derived organoids can be used to predict the clinical response of breast cancer patients to neoadjuvant chemotherapy in vitro and to screen drugs that have different effects on different patients.