Investigators hope that a phase 2 clinical trial currently underway at Roswell Park Comprehensive Cancer Center will help guide future decisions about neoadjuvant chemotherapy for patients with HER2+ breast cancer, which accounts for about 20% of all breast cancer diagnoses in the United States. The ultimate goal: to provide a tool that can help medical oncologists predict a patient’s response to standard-of-care chemotherapy in order to determine the optimal course of treatment before surgery.

Ellis Levine, MD, Chief of Breast Medicine at Roswell Park, serves as site principal investigator for “Testing the Role of FDG-PET/CT to Predict Response to Therapy Prior to Surgery for HER2-positive Breast Cancer, The DIRECT Trial” (NCT05710328). Sponsored by Eastern Cooperative Oncology Group (ECOG-ACRIN Cancer Research Group), the study is open to both men and women 18 and older who have HER2+, stage 2a-3c breast cancer.

The protocol centers on FDG-PET/CT, which combines the imaging capabilities of CT with a PET scan that uses the glucose analog fludeoxyglucose-18 (F-18 FDG) as a radioactive tracer. FDG-PET can pinpoint metabolically active malignant lesions in breast cancer and can be used both to stage the disease and monitor response to treatment. Previous studies have shown that combining FDG-PET with CT provides greater diagnostic accuracy in the detection of distant metastases. It can also differentiate between benign and malignant lesions and locate an unknown primary tumor when the disease has already metastasized at the time of initial presentation.

“Having reliable PET/CT information early, about two weeks into treatment, allows us to potentially personalize therapy,” explains Dr. Levine.

“This information will have several possible applications. If we start with a less-aggressive — and therefore less-toxic — regimen and achieve an excellent PET/CT response, we can continue that regimen with confidence. But if it results in a suboptimal PET/CT response, the treatment regimen can be escalated, or made more aggressive.

“On the other hand, if we begin with an aggressive regimen and achieve an excellent PET/CT response in two weeks, it’s possible that the treatment program can be completed sooner than planned, with an excellent result — or, alternatively, that therapy can be de-escalated so it is less-aggressive and less-toxic, while still achieving an excellent outcome.”

Patients enrolled in the trial will received FDG intravenously, undergo PET/CT and receive standard-of-care chemotherapy prior to standard-of-care surgery.

This clinical trial has an expected enrollment of 235 nationwide.