Project 462212

Breast cancers sensitive to the female hormone estrogen (ER+) are the most common subtype of breast cancer, and represent a majority of cases of incurable metastatic disease in Canada and worldwide. Recently, a new class of targeted therapy, called CDK4/6-inhibitors (CDK4/6i), has been introduced as standard treatment for patients with newly diagnosed, metastatic ER+ breast cancer. These drugs improve disease control, quality of life, and survival. However, they are not curative, and eventually the cancers grow and spread despite treatment. Currently, there is uncertainty about the optimal treatment for patients after such "resistance" to CDK4/6i develops. Studies examining ER+ breast cancers that have become resistant have identified different ways that resistance can occur in different patients, suggesting that optimal treatment must be individualized. Liquid biopsy, which allows tumor cells (circulating tumor cells) or small fragments of genetic material from tumor cells to be detected in the blood (circulating tumor DNA, ctDNA), offers a way to precisely identify the specific alterations in an individual patient's cancer in real time at the time a new line of treatment is needed. Conducted by the Canadian Cancer Trials Group, this pan-Canadian study will investigate how the use of liquid biopsy can precisely match patients to promising new therapeutic strategies, tailored to their tumor's unique identity. In addition, we will study changes that are detectable in liquid biopsies that occur before drug resistance develops on standard CDK4/6i treatment, in order to develop future strategies to intercept resistance, by changing or optimizing treatment before tumor growth and symptomatic progression occurs. This work represents an important step towards using liquid biopsy to its maximum potential to improve the treatment, quality of life, and outcomes for patients with metastatic ER+ breast cancer through individualized treatment delivery.