New ultrasound-based imaging method, mULM, for diagnosing breast cancer and assessing response to neoadjuvant therapy

Breast cancer (mammary carcinoma) is a malignant disease of the mammary gland tissue characterized by the uncontrolled proliferation of mammary gland cells. Treatment of the disease depends on numerous factors, such as the patient’s overall health, the tumor’s growth rate (Ki-67 index), the presence of detectable hormone receptors on the surface of the cancer cells (estrogen receptor-positive, progesterone receptor-positive), and the increased expression of the HER2 receptor on the cells (HER2-positive). If none of these receptors are present, the cancer is referred to as triple-negative breast cancer. The stage of the disease is also very important: While in the locally confined stage (stages 1–2) the disease is limited to the breast, the locally advanced stage (stage 3) means that the tumor is already larger or that lymph nodes are involved. Treatment for stage 1–3 triple-negative breast cancer typically involves preoperative chemotherapy (neoadjuvant therapy) to shrink the tumor, followed by surgical removal of the tumor. Follow-up drug treatment (adjuvant therapy) is often recommended to kill any remaining cancer cells.

The method of choice for diagnosing breast cancer in women aged 50 and older is bilateral mammography. For women under 40, an ultrasound examination is performed first, and for women aged 40 and older, ultrasound may be used in addition to mammography. If breast cancer is suspected based on imaging results, a tissue sample is taken (biopsy) and examined histologically.

Motion-Model Ultrasound Localization Microscopy (mULM) is an innovative imaging method based on ultrasound that enables the precise visualization of tiny blood vessels that would not be detectable with conventional ultrasound. This is crucial because tumors often have a different vascular pattern than healthy tissue. In addition, mULM imaging can visualize changes during treatment (e.g., neoadjuvant chemotherapy) even before they are detectable in the tumor mass. To achieve this, microbubbles of an already approved contrast agent (SonoVue®) are injected into the bloodstream. These are then tracked over time in multiple ultrasound images. The positions in the individual images are then combined to create a high-resolution map of the blood vessels. mULM is currently being used experimentally and in clinical trials.

The aim of this study is to investigate the accuracy of the mULM imaging diagnostic method. In Part A of the study, the optimal contrast agent dose and injection rate will first be determined; these will then be used in Parts B and C of the study. In Part B of the study, mULM imaging will be used to assess the tumor’s response to neoadjuvant chemotherapy. To this end, the tumor’s blood flow will be examined at three different time points during therapy. In Part C, patients with suspected breast cancer will be examined—that is, when an abnormal lump has been detected in the breast but it is not yet certain whether it is cancer. First, an ultrasound without contrast agent is performed. This involves a standard ultrasound (B-mode) followed by elastography (tissue deformation ultrasound), which measures how “soft” or “hard” the tissue is. Next, the largest area suspected of containing a tumor is examined using mULM. Finally, a tissue sample is taken and the collected material is subjected to comprehensive analysis. Both patients and medical staff know which diagnostic method is being used (open-label study design).

Women aged 18 and older with suspected breast cancer or histologically confirmed triple-negative breast cancer who are scheduled to undergo neoadjuvant chemotherapy prior to surgery are eligible to participate in this study.