MRI evaluation of axillary and intramammary lymph nodes in the postoperative period

Abstract Our study aimed to evaluate if breast‐conserving surgery and adjuvant treatment could affect the morphological features of axillary and intramammary lymph nodes on magnetic resonance imaging (MRI) in patients with invasive breast cancer and clinically negative axilla. In this single‐center study, we retrospectively evaluated 50 patients who had (a) breast‐conserving surgery, (b) clinically negative axilla, (c) preoperative MRI within 3 months before surgery, and (d) postoperative MRI within 12 months after surgery. Axillary and intramammary lymph nodes on postoperative MRI were identified and then compared with preoperative MRI by two breast radiologists with regards to the following: enlargement, cortical thickening, presence of fatty hilum, irregularity, heterogeneity, matting, and axillary lymph node asymmetry. Three hundred and two axillary and eight intramammary lymph nodes were evaluated. Enlargement and cortical thickening were seen in 5/50 (10%) patients in three axillary and two intramammary lymph nodes. None of the lymph nodes on postoperative MRI demonstrated occurrence of lack of fatty hilum, irregularity, heterogeneity, matting or axillary lymph node asymmetry. No evidence of recurrence was observed on 2‐year follow‐up. Lymph node enlargement and cortical thickening may be observed in a few patients in the postoperative period. Nevertheless, in patients with clinically negative axilla, these changes in morphology are often related to treatment rather than malignancy and favor short‐term follow‐up as an alternative to lymph node biopsy.


| INTRODUC TI ON
Nodal status in breast cancer is one of the determining factors for staging, treatment, and prognosis. Axillary lymph node (LN) dissection is the traditional surgical approach for assessment of nodal staging. In the last two decades, sentinel LN biopsy has become the method of choice for selecting patients with negative LNs in whom axillary LN dissection can be avoided, reducing the incidence of postsurgical complications. 1 More recently, the American College of Surgeons Oncology Group Z0011 study demonstrated that axillary LN dissection can also be avoided in patients with 1-2 positive LNs on sentinel LN biopsy if they meet certain criteria. 2,3 Although there are studies that demonstrate that preoperative imaging of LNs is still necessary, some authors believe that the importance of preoperative evaluation of LNs has been diminished. [4][5][6][7] While these advances impact nodal staging in the preoperative setting, there is a need to also advance the assessment of LNs following breast-conserving surgery to determine the possibility of recurrence. In this setting, patients treated for breast cancer will be followed with imaging. While some patients will be followed with mammography and ultrasound only, others will also undergo magnetic resonance imaging (MRI) to rule out recurrence. [8][9][10] In comparison with ultrasound and mammography, MRI not only has a higher sensitivity for detecting recurrence in the breast but is also able to visualize some LNs that are not assessible on other modalities. 11 Several studies have investigated MRI for LN assessment in breast cancer. [12][13][14][15][16][17][18][19][20][21][22][23][24] Whereas morphology may be preserved in some LNs with metastatic infiltration, benign processes like inflammatory response may also cause significant changes in LN morphology. To this date, there is no consensus in the literature about which MRI parameters should be used to raise suspicion. Nonetheless, the imaging features such as presence of enlargement, cortical thickening, lack of fatty hilum, irregular contours, matting, and axillary nodal asymmetry have been reported to be associated with malignant infiltration. [15][16][17][18][19][20][21][22] Moreover, the investigation of LNs in breast cancer has mainly focused on the pretreatment setting [12][13][14][15][16][17][18][19][20][21][22][23][24] and their imaging features on MRI in the postoperative period have not been fully explored.
Changes in imaging features may be benign sequelae of surgery and radiation therapy, or may be related to postsurgical complications, such as infection that can be difficult to distinguish from recurrent or metastatic disease. 25 In this context, the aim of this study was to evaluate if breastconserving surgery and adjuvant treatment affect the morphological features of axillary and intramammary LNs on MRI in patients with invasive breast cancers and negative axillae.

| MATERIAL S AND ME THODS
The Institutional Review Board approved this single-center Health Insurance Portability and Accountability Act compliant retrospective study and waived the requirement for patient informed consent.

| Patients
The institutional data base was queried for consecutive patients from January 2010 to December 2015 who matched the following criteria: (a) breast-conserving surgery for invasive breast cancer, (b) clinically negative axilla with negative sentinel LN biopsy, (c) preoperative MRI within 3 months before surgery, and (d) postoperative MRI within 12 months after surgery. Exclusion criteria were (a) poor imaging quality, (b) axillary LN dissection, and (c) neoadjuvant treatment for breast cancer. Fifty patients were included in the study with one patient presenting with bilateral breast cancer.

| Data analysis
The information obtained from medical records was reviewed for patient age, date and type of surgery, dates of preoperative and postoperative MRI studies, and adjuvant treatments received including radiation, chemo and hormone therapies. Preoperative and follow-up consultations and imaging reports were also reviewed for evidence of nodal metastatic disease or recurrence.

| Histopathology
The histopathology findings from the surgical specimens of the primary tumor were considered as the standard of reference. Reports were reviewed for tumor type and immunohistochemical receptor status, including estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The tumors were classified into molecular subtypes via immunohistochemical surrogates.

| Image analysis
The preoperative and postoperative MRIs were reviewed in consensus by two radiologists (JVH and KP) specialized in breast imaging with 6 and 12 years of experience, respectively. The radiologists were blinded for clinical data. The axillary and intramammary LNs ipsilateral to the operated breast were first identified on the postoperative MRI and then compared with the preoperative MRI. LNs were evaluated on non-fat saturated T1-weighted, fat saturated T1and T2-weighted, and contrast enhanced T1-weighted sequences regarding the following: enlargement, cortical thickening, presence of fatty hilum, irregularity, heterogeneity, matting and axillary LN asymmetry. Additionally, measurements of the long axis and the cortical thickness on the largest axillary and intramammary LNs identified in each case were done on the slice where fatty hilum was best visualized. If there was a lack of a fatty hilum, the short axis was considered as the cortical thickness.

| Statistical analysis
Statistical analyses were performed using SAS statistical software version 9.4 (SAS Institute, Cary, NC). Categorical variables were summarized using frequencies and percentages for categorical variables. Continuous variables were summarized using medians and ranges. Long axis and cortical thickness of LNs were presented as mean ± standard deviation measured in millimeters. Measurements were done on a "nodeby-node" basis and bilateral nodes in the same patient were assumed to be non-correlated. We assessed differences between groups using t tests and the log-rank test. All tests were two sided and we considered P < 0.05 to be indicative of statistically significant differences.

| Axillary lymph nodes
Visual assessment of axillary LNs demonstrated that none of the patients presented with a new lack of a fatty hilum, irregularity, heterogeneity, matting or axillary LN asymmetry on postoperative MRI in comparison with the preoperative study. In 3/50 (6%) patients,      20 Another feature frequently investigated is the presence of a fatty hilum on LNs. 18,20 Although the absence of fatty hilum is frequently seen in metastatic LNs, this can also be seen in up to one-third of benign LNs. 16  Our retrospective study has some limitations. Only one patient had an MRI study within 3 months after surgery; thus, insights into the early postoperative period are limited. We only included patients with clinically negative axilla and breast-conserving surgery; thus, our results should only be considered relevant for this specific population. In addition, our relatively small population can also be seen as one limitation; thus, prospective studies with a larger number of patients are needed to better understand the imaging aspects of LNs on MRI in the postoperative period. Lastly, even though the postoperative MRIs were performed during or after completion of adjuvant treatment, and patients with postoperative nodal enlargement showed no signs of recurrence on 2-year follow-up, there is a slight possibility that some LN enlargements could be attributed to metastatic disease in patients with false negative sentinel LN biopsy.

| Intramammary lymph nodes
In conclusion, LN enlargement and cortical thickening may be observed in a few patients in the postoperative period. In patients with clinically negative axilla, these changes in morphology are often related to treatment and favor short-term follow-up as an alternative to LN biopsy.

ACK N OWLED G M ENTS
This study received funding from the NIH/NCI Cancer Center Support Grant (P30 CA008748) and the Breast Cancer Research Foundation.