Characterizing Occult Nodal Disease Within a Clinically Node-Negative, Neoadjuvant Breast Cancer Population


      • cN0 ER+/HER- patients had higher risk of nodal upstaging compared to HER2+ & TNBC.
      • MRI or axillary ultrasound did not modulate risk for nodal upstaging.
      • Compared to NAC, use of NET did not significantly modulate risk for nodal upstaging.



      Neoadjuvant therapy aims to preoperatively downstage breast cancer patients. We evaluated nodal upstaging in clinically node-negative (cN0) patients receiving neoadjuvant chemotherapy (NAC) and neoadjuvant endocrine therapy (NET).


      cN0 patients undergoing neoadjuvant therapy from 2009 to 2018 were reviewed. Univariate and multivariate analyses evaluated rates of nodal upstaging.


      A total of 228 cN0 patients with a mean age of 55 years underwent neoadjuvant therapy for Stage I-III invasive carcinoma. Subtypes included ER+/HER2- = 93 (40%), HER2+ = 61 (27%), and triple negative (TNBC) = 74 (33%). Among ER+/HER2- patients, 65 (70%) underwent NET. Overall, 49 patients (21%) were upstaged due to occult nodal disease. Factors associated with higher rates of occult nodal disease included advanced stage on initial presentation (P = .008), larger presenting tumor size (P = .009), low/intermediate tumor grade (P = .025), and ER+/HER2- subtype (P < .001); incidence of occult nodal disease by subtype included: ER+/HER2- = 37%, HER2+ = 15%, TNBC = 8%. Patients experiencing a breast pCR had a significantly lower rate of nodal upstaging compared to those with residual tumor (4% vs. 96%, P < .001). On multivariate analysis, ER+/HER- patients exhibited higher risk of occult nodal disease when compared to patients with HER2+ (odds ratio [OR] = 3.4, 95% CI, 1.2-9.8, P = .003) and TNBC (OR = 5.7, 95% CI, 1.7-19.6, P = .003). Comparing NAC vs. NET in ER+/HER2- patients showed no difference in rates of occult nodal disease (39% vs. 35%, P = .13).


      ER+/HER2- subtype carries higher risk for occult nodal disease after neoadjuvant therapy; NAC versus NET in these patients does not affect nodal upstaging.


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