Diagnostic Performance of [18F]FES PET/CT for Axillary LN Metastasis in ER-positive Breast Cancer

Breast cancer is the most common cancer among women, with around 310,000 new cases expected in the U.S. in 2024, accounting for 32% of all cancers diagnosed in women. About 75% of breast cancers express estrogen receptors (ER) at the time of diagnosis, and the axillary lymph nodes are the most common site for metastasis. Around 34% of breast cancer patients present with lymph node metastasis, with 24% classified as pN1 (1-3 lymph nodes) and 10% as pN2 or higher (4 or more lymph nodes) according to the AJCC staging system. The presence and extent of lymph node metastasis are critical in determining the stage of breast cancer, as well as predicting the likelihood of recurrence and survival after surgery. Lymph node involvement also guides decisions about the scope of surgery and systemic therapy. To minimize complications such as lymphedema, axillary lymph node dissection (ALND) has become less invasive over time. The ACOSOG Z0011 trial demonstrated that patients with 1-2 lymph node metastases detected via sentinel node biopsy (SNB), who had no clinically evident axillary lymph node metastasis, could avoid ALND without negatively affecting their prognosis. As a result, preoperative evaluation of axillary lymph node metastasis has become increasingly important in determining the appropriate surgical approach. For systemic treatment, the NCCN guidelines recommend adjuvant chemotherapy for estrogen receptor-positive, HER2-negative breast cancer patients with pN2 or higher lymph node involvement after surgery. In cases of pN1 or pN0 (with tumors larger than 0.5 cm), the decision to administer adjuvant chemotherapy is based on the recurrence risk score from a 21-gene assay. \[18F\]FES PET/CT has recently gained attention as an imaging modality for breast cancer due to its ability to evaluate ER status with high concordance to immunohistochemistry and detect metastasis. The NCCN guidelines now recommend its use in cases of recurrent or metastatic ER-positive breast cancer. In our previous research, \[18F\]FES PET/CT has a sensitivity of 77% and specificity of 100% for breast cancer diagnosis when compared to histopathological findings. Although its accuracy for detecting axillary lymph node metastasis specifically has not been thoroughly studied, it has shown potential in identifying difficult-to-detect axillary metastases. In one study, the use of \[18F\]FES PET/CT led to changes in treatment plans for about 26% of patients, particularly by identifying lymph node metastases that were missed by standard imaging techniques. In addition to its use in recurrent or metastatic breast cancer, \[18F\]FES PET/CT is being investigated for its utility in evaluating axillary lymph nodes and staging early breast cancer. Preliminary studies at our hospital on invasive lobular breast cancer patients have shown that \[18F\]FES PET/CT has favorable diagnostic accuracy for detecting axillary lymph node metastasis. While PET resolution limits its ability to assess micrometastases, the high specificity and positive predictive value suggest that it could accurately predict the presence and burden of axillary lymph node metastasis in estrogen receptor-positive breast cancer.