UCSF

Organoid culturing is a three-dimensional tissue culturing method with significant promise for increasing our ability to model cancer subtypes in the laboratory. We modified tissue processing methods and used a natural hydrogel (GrowDex) as well as basement membrane extract (BME) to optimize conditions for growth and immunostaining of breast cancer organoid cultures. We focused on breast cancers that were Estrogen Receptor (ER) and/or Progesterone Receptor (PR) positive, generating cultures of residual disease after treatment with neoadjuvant endocrine therapy in the Investigation of Serial studies to predict your therapeutic response with Imaging and Molecular AnaLysis 2 (NCT01042379, I-SPY2) clinical trial. Patients on an Endocrine Optimization Protocol (EOP) in I-SPY2 were treated with amcenestrant alone or in combination with an aromatase inhibitor or a CDK4/6 inhibitor prior to specimen collection and culturing. The goal of these studies was to generate conditions for successful propagation of residual breast cancer resistant to primary treatment, including verification of expected protein expression patterns, for future experiments to test new therapies for ER+ breast cancer resistant to endocrine therapy.