Magnetic resonance imaging (MRI) of the axilla after neoadjuvant chemotherapy is no more accurate than a clinical exam alone in predicting sentinel lymph node pathology in breast cancer patients with clinical N1 (cN1) disease. Further, abnormal axillary lymph nodes on MRI should not preclude sentinel lymph node biopsy.
The optimal method to select patients for axillary staging with sentinel lymph node biopsy after neoadjuvant chemotherapy has been unclear. Together with our colleagues at Memorial Sloan Kettering Cancer Center, we conducted the largest study to date examining the accuracy of MRI in predicting residual axillary lymph node disease after neoadjuvant chemotherapy among patients with clinical N1 breast cancer. Our research, published recently in the journal Annals of Surgical Oncology, was also the first to compare the accuracy of MRI with a clinical exam. (1)
In our study, 30 percent of patients (55 of 182) had abnormal lymph nodes on MRI. Among this group, 58 percent (32 of 55 patients) had a positive sentinel lymph node on final pathology compared with 42 percent (53 of 127 patients) with no abnormal lymph nodes on MRI, and 52 percent (45 of 87 patients) had only a clinical exam (p = 0.09). (1)
MRI sensitivity was 38 percent, specificity was 76 percent, and overall accuracy in predicting sentinel lymph node status was 58 percent. Therefore, if we had triaged patients based on abnormal MRI findings alone, 42 percent of patients with a positive MRI finding yet negative disease on final pathology (23 of 55 patients) would have undergone an unnecessary axillary dissection. (1)
Our findings indicate that a negative clinical exam alone is sufficient to determine eligibility for a sentinel lymph node biopsy and that abnormal lymph nodes on MRI should not alter surgical planning. This approach will help ensure that the right patients receive axillary dissection, limiting treatment and the risk of lymphedema to patients who would benefit from the procedure.
Axillary Dissection for Clinically Positive Lymph Nodes
Historically, all patients with clinically positive axillary lymph nodes treated with neoadjuvant chemotherapy had an axillary dissection, regardless of treatment response. A high rate of complete response on pathology results led to clinical trials exploring the feasibility and accuracy of sentinel lymph node biopsy in node-positive patients who downstaged after neoadjuvant chemotherapy. (2) These trials found that the false-negative rate was less than 10 percent for patients who were node-positive at presentation and had three or more sentinel nodes retrieved after neoadjuvant chemotherapy. (3), (4), (5)
As a result, the National Comprehensive Cancer Network endorsed sentinel lymph node biopsy in patients with clinically positive axillary nodes who downstage following neoadjuvant chemotherapy. (6) However, the best method for selecting patients for axillary staging has been unclear, and practices vary. In patients with clinically palpable disease after neoadjuvant chemotherapy, a sentinel node biopsy is not appropriate because it has a false-negative rate of 19 percent. (4)
Prospective trials have found a positive predictive value of 65 to 89 percent for detecting residual axillary disease with a clinical exam among patients with palpable disease following neoadjuvant chemotherapy. (5), (7) At MSK, 78 percent of our cN1 patients with palpable axillary disease after neoadjuvant chemotherapy who underwent axillary dissection had positive nodes on final pathology. (8) Together, these data support axillary dissection as the appropriate procedure for patients with clinically palpable disease after neoadjuvant chemotherapy. Among those with a negative axillary clinical exam, about 47 percent will have residual nodal disease. (7), (8)
MRI is the most sensitive imaging modality for assessing residual disease following neoadjuvant chemotherapy and is widely used to assess treatment response. (9), (10) However, in patients with a negative clinical exam, abnormal findings on MRI may lead to axillary dissection.
We assessed the accuracy of clinical exams alone compared to clinical exams plus MRI in determining the status of axillary sentinel lymph nodes in cN1 patients with a negative axillary clinical exam following neoadjuvant chemotherapy.
Our cohort consisted of 269 patients with a median age of 49 years. Most tumors had ductal histology (94 percent) and were classified as high grade (90 percent). Following neoadjuvant chemotherapy, 87 patients (32 percent) had a clinical exam alone, and 182 patients (68 percent) had a clinical exam and an MRI. Tumor histology, T stage, hormone receptor status, the number of sentinel nodes removed, and the number of positive sentinel nodes were comparable between the groups. (1)
We found no difference in the frequency of positive sentinel nodes on final pathology based on whether patients had received a clinical exam alone, a positive MRI finding, or a negative MRI finding (p = 0.09). (1)
MRI predicted the pathological status of sentinel nodes with a sensitivity of 38 percent and a specificity of 76 percent. The overall accuracy of MRI to predict the sentinel node status was 58 percent. (1)
Hypothetically, if we had triaged patients to axillary dissection based on abnormal MRI findings, 23 of 55 patients (42 percent) with a suspicious MRI finding yet negative final sentinel node pathology would have had an unnecessary procedure. (1)
The accuracy of MRI increased to 62 percent when residual disease was observed in both the breast and axilla, but triaging patients based on these findings would still have resulted in 30 percent of patients with negative sentinel nodes having an axillary dissection. (1)
Overall, our findings indicate that MRI after neoadjuvant chemotherapy is no more accurate than a clinical exam alone in predicting sentinel lymph node pathology in patients with clinical N1 disease. Abnormal lymph nodes on MRI should not exclude proceeding to sentinel lymph node biopsy for further evaluation.
Advancing Breast Cancer Care
At MSK, we are committed to maximizing cancer outcomes for our patients. At the same time, we look for ways to help patients avoid the toxic effects of cancer treatments whenever possible.
We are currently conducting a randomized phase III clinical trial to evaluate the effectiveness of axillary radiation therapy compared to standard surgical removal of axillary nodes in patients with positive sentinel nodes after neoadjuvant chemotherapy.
MSK physicians have pioneered microsurgical techniques that redirect or reconnect small lymphatic blood vessels to help prevent and treat lymphedema. MSK is also the only cancer center with an active lymphedema surgical program supported by a dedicated lymphedema research laboratory.
This study was funded in part by a National Institutes of Health/National Cancer Institute Cancer Center Support Grant (P30 CA008748). It was presented in a podium format at the Society of Surgical Oncology’s 72nd Annual Cancer Symposium.
Dr. Moo has no conflict-of-interest disclosures to report. Dr. Morrow has received speaking honoraria from Genomic Health and Roche.