A Phase 2, Open-label, Non-randomized, Single-center Study to Explore the Diagnostic Performance of [18F]FES PET/CT for the Assessment of Axillary Lymph Node Metastasis in Invasive Lobular Carcinoma of the Breast

Invasive lobular carcinoma (ILC) is known to account for about 10-15% of all invasive breast cancer and is the second most common subtype of breast cancer following invasive ductal carcinoma (IDC). ILC is histologically characterized by the loss of E-cadherin involved in cell adhesion, which contributes to the growth and infiltration of tumors in the characteristic non-adhesive single cell layer pattern of ILC]. Therefore, ILC often has no tumors detected by physical examinations and the sensitivity of mammography being reported to be 34%, which is much lower than IDC (81%). Therefore, the diagnosis of ILC is often delayed, the tumor size is larger and the stage is higher than that of IDC at the first visit. The diagnostic accuracy of breast ultrasound for axillary lymph node metastasis is reported as 55-92% for sensitivity and 80-97% for specificity. However, in the case of ILC, the diagnostic performance is significantly lower than this. According to the previous study on ILC, mammography had 7% of sensitivity, ultrasound had 26%, and MRI had 7% in diagnosing axillary lymph node metastasis with 38% of patients having false positive results for axillary lymph node metastasis. This is related to ILC-specific metastasis patterns in which only cells are replaced by cancer cells while maintaining the normal structure of the lymph node and the absence of desmoplastic reaction. The NCCN guideline recommends that during axillary lymph node resection, resection is performed up to level III if lymph node metastasis is confirmed or suspected in axillary level II or III. Preoperative chemotherapy should be considered for lymph node metastasis of cN3 or Bulky or matted cN2 stage. Considering the limited diagnostic accuracy of those standard imaging tests for diagnosis of axillary lymph node metastasis, [18F]FES PET/CT may help change treatment strategy, such as changing the extent of axillary lymph node resection or performing neoadjuvant chemotherapy instead of upfront surgery in patients with ILC. In addition, considering that high rate of distant metastasis and limited diagnostic accuracy of preexisting imaging modality in ILC, [18F]FES PET/CT is likely to help treatment decision making by discovering unexpected distant metastases. It is reported that the implementation of [18F]FES PET/CT contributed to the change in treatment policy in about 26% of patients compared to conventional standard imaging and [18F]FDG PET/CT. Currently in South Korea, reimbursement of [18F]FES PET/CT is limited to patients with recurrent or metastatic breast cancer whose lesions are located in the cervical spine, upper thoracic, pelvic, peritoneum, pleural, and mediastinal lymph nodes.