Fat-enlarged axillary lymph nodes are associated with node-positive breast cancer in obese patients

Abstract

Purpose Obesity associated fat infiltration of organ systems is accompanied by organ dysfunction and poor cancer outcomes. Obese women demonstrate variable degrees of fat infiltration of axillary lymph nodes (LNs), and they are at increased risk for node-positive breast cancer. However, the relationship between enlarged axillary nodes and axillary metastases has not been investigated. The purpose of this study is to evaluate the association between axillary metastases and fat-enlarged axillary nodes visualized on mammograms and breast MRI in obese women with a diagnosis of invasive breast cancer. Methods This retrospective case–control study included 431 patients with histologically confirmed invasive breast cancer. The primary analysis of this study included 306 patients with pre-treatment and pre-operative breast MRI and body mass index (BMI) > 30 (201 node-positive cases and 105 randomly selected node-negative controls) diagnosed with invasive breast cancer between April 1, 2011, and March 1, 2020. The largest visible LN was measured in the axilla contralateral to the known breast cancer on breast MRI. Multivariate logistic regression models were used to assess the association between node-positive status and LN size adjusting for age, BMI, tumor size, tumor grade, tumor subtype, and lymphovascular invasion. Results A strong likelihood of node-positive breast cancer was observed among obese women with fat-expanded lymph nodes (adjusted OR for the 4th vs. 1st quartile for contralateral LN size on MRI: 9.70; 95% CI 4.26, 23.50; p < 0.001). The receiver operating characteristic curve for size of fat-enlarged nodes in the contralateral axilla identified on breast MRI had an area under the curve of 0.72 for predicting axillary metastasis, and this increased to 0.77 when combined with patient and tumor characteristics. Conclusion Fat expansion of axillary lymph nodes was associated with a high likelihood of axillary metastases in obese women with invasive breast cancer independent of BMI and tumor characteristics.

Association between Fat-Infiltrated Axillary Lymph Nodes on Screening Mammography and Cardiometabolic Disease

“…The adverse health impact of ectopic fat in other organs has also been linked to poor cancer outcomes. A recent study showing a higher likelihood of nodal metastases in obese women with fat enlarged axillary nodes further supports our hypothesis that ectopic nodal fat may negatively impact LN function (15).…”

“…The adverse health impact of ectopic fat has also been identified in cancer outcomes. We recently reported a positive association between fat enlarged axillary nodes and nodal metastasis among women with obesity who developed invasive breast cancer independent of BMI and tumor characteristics, supporting our hypothesis that ectopic nodal fat impacts nodal function as seen with ectopic adipose deposition in other organs (12). Our current study does not evaluate potential causal pathways, and additional studies are needed to better understand the relationship between ectopic nodal fat and cardiometabolic disease.…”

“…Variable LN visibility is due to the differences in patient body habitus and technical differences related to patient positioning at the time of the exam. No appreciable differences have been reported among women with and without visible LNs (15,29). Nonetheless, inconsistent mammographic visualization of axillary LNs may introduce bias when evaluating the association between fatty nodes and cardiometabolic disease status.…”

“…The largest visible axillary LN (index node) was chosen for image analysis by two readers, the breast imaging radiologist (RDA) and a senior radiology resident (RS). Independent measurements of the largest index LN were then obtained along the LNs’ greatest longitudinal axis by both readers, as previously described (12,15). Mammograms were classified as fat-infiltrated if the index LN measured ≥ 18mm, or as normal if the index LN measured < 18mm, using the threshold identified by prior studies (12,15).…”

“…For each patient, the mediolateral oblique (MLO) view with the largest visible axillary LN (index node) was selected for image analysis by a breast imaging radiologist with 18 years of experience. The index node was measured along its greatest longitudinal axis and categorized as fat-enlarged or normal based on the morphology of the fatty hilum and overall node size greater than 18 mm, using the size threshold identified in prior studies (9,12). A senior radiology resident independently analyzed the screening mammograms and classified nodes as normal or fatty based using the same criteria.…”