Ten-year locoregional recurrence risks in women with nodal micrometastatic breast cancer staged with axillary dissection

Purpose: To compare the locoregional recurrence (LRR) rates in patients with nodal mirometastases (pNmic) with those in patients with node-negative (pN0) and macroscopic node-positive (pNmac) breast cancer; and to evaluate the LRR rates according to locoregional treatment of pNmic disease.

Methods and materials: The subjects were 9,616 women diagnosed between 1989 and 1999 with Stage pT1-T2, pN0, pNmic, or pNmac, M0 breast cancer. All women had undergone axillary dissection. The Kaplan-Meier local recurrence, regional recurrence, and LRR rates were compared among those with pN0 (n=7,977), pNmic (n=490) and pNmac (n=1,149) and according to locoregional treatment. Multivariate analysis was performed to identify the significant factors associated with LRR.

Results: The median follow-up was 11 years. The 10-year Kaplan-Meier recurrence rate in the pN0, pNmic, and pNmac cohorts was 6.1%, 6.8%, and 8.7% for local recurrence; 3.1%, 6.2%, and 10.3% for regional recurrence; and 8.0%, 11.6%, and 15.2% for LRR, respectively (all p<.001). In the pNmic patients, the 10-year regional recurrence rate was 6.4% with breast-conserving surgery plus breast radiotherapy (RT), 5.4% with breast-conserving surgery plus locoregional RT, 4.6% with mastectomy alone, 11.1% with mastectomy plus chest wall RT, and 10.7% with mastectomy plus locoregional RT. In patients with pNmic disease and age<45 years, Grade 3 histologic features, lymphovascular invasion, nodal ratio>0.25, and estrogen receptor-negative disease, the 10-year LRR rates were 15-20%. On multivariate analysis of the entire cohort, pNmic was associated with greater LRR than Stage pN0 (hazard ratio [HR], 1.6; p=.002). On multivariate analysis of pNmic patients only, age<45 years was associated with significantly greater LRR (HR, 1.9; p=.03), and trends for greater LRR were observed with a nodal ratio>0.25 (HR, 2.0; p=.07) and lymphovascular invasion (HR, 1.7; p=.07).

Conclusion: Women with pNmic had a greater risk of LRR than those with pN0 disease. Patients with pNmic in association with young age, Grade 3 histologic features, lymphovascular invasion, nodal ratio>0.25, and estrogen receptor-negative disease experienced 10-year LRR rates of ∼15-20%, warranting consideration of locoregional RT.