Now Enrolling: The DIRECT study is testing how well FDG-PET/CT imaging can predict if treatment is working prior to surgery for patients with HER2-positive breast cancer

Breast cancer is the second most common cancer in women in the United States—and about one in five breast cancer diagnoses are associated with the HER2 protein (HER2 stands for human epidermal growth factor receptor 2). This protein promotes the growth of cancer cells. If breast cancer cells have higher-than-normal levels of HER2, the cancer is called HER2-positive.

Doctors usually treat patients with HER2-positive breast cancer using two to three chemotherapies plus HER2-targeting drugs. This can be followed by surgery and then additional therapy. The treatments given before surgery are usually very effective—but unfortunately, the most effective ones cause significant side effects.

Due to this delicate balance between efficacy and toxicity, doctors closely monitor how well treatment is working through physical examination and various imaging techniques. The goal is to deliver the appropriate therapy as tailored as possible to individual patient needs, to maintain efficacy but minimize side effects.

Recent research suggests that of all the imaging methods, FDG-PET/CT may provide the most accurate indication of which patients will not have a good response to treatment prior to surgery. The EA1211/DIRECT study is evaluating whether FDG-PET/CT is useful for this purpose.

The study aims to find out if this new approach can be used to make personalized treatment decisions for patients with HER2-positive breast cancer in the future. If confirmed, the study would have a significant clinical impact. For example, for patients unlikely to have a good response to initial treatment, additions or changes could be made to increase the likelihood of benefit.

To be eligible for the DIRECT trial, patients must be at least 18 years of age and have had no prior treatment for their stage 2 to stage 3c HER2-positive breast cancer. This includes no surgery, chemotherapy, hormonal therapy, radiation, or experimental therapy. Their cancer cells may be either estrogen receptor (ER)-positive or ER-negative. Tumor size must be larger than 2 centimeters and may or may not have spread to surrounding lymph nodes.

Approximately 235 patients will take part in the DIRECT study. All patients will have a baseline FDG-PET/CT scan, then start chemotherapy and targeted therapy. Around two to three weeks later, patients will have a second FDG-PET/CT scan and then continue the usual course of treatment. The study team will follow all patients for at least three years.

EA1211/DIRECT is led by Heather Jacene, MD of Dana-Farber Cancer Institute.

Learn more about EA1211/DIRECT at ecog-acrin.org.