Can we identify the group of small invasive (T1a,b) breast cancers with minimal risk of axillary lymph node involvement? A pathohistological and DNA flow cytometric study.

The goal of this study was to identify a group of small (≤1cm) breast cancers (T1a,b) with a particularly low probability of axillary lymph node metastases, where routine axillary staging may be unnecessary. We retrospectively analyzed 152 T1a,b breast carcinomas with axillary dissection surgically removed at Clinical Hospital Center Split (Croatia) in the period from 1997 to 2006. The analysis included 40 T1a,b cancers with, and 112 T1a,b cancers without axillary lymph node metastases. The basic morphological features of cancers were investigated histologically, while hormone receptors and HER2/neu were investigated immunohistochemically with an additional CISH analysis of HER2/neu 2+ cases. The ploidy and S-phase fraction were determined by DNA flow cytometry. The association of the investigated features with the likelihood of axillary lymph node metastases was analyzed by univariate and multivariate analysis. The univariate analysis showed that lymph node metastases were associated with tumor size (T1a/T1b; p=0.026), histological type (ductal/non-ductal; p=0.014), lymphovascular invasion (p<0.001), HER2/neu expression (p=0.04), ploidy (p=0.027), and combined values of ploidy and S-phase fraction (p=0.025). The lymphovascular invasion was the only independent factor associated with axillary nodal metastases (p=0.01). In the group of T1a,b cancers without lymphovascular invasion, HER2/neu expression (p=0.021) and combined values of ploidy and S-phase fraction (p=0.016) were independent factors associated with axillary lymph node metastases. This study showed that diploid T1a,b cancers with low S-phase fraction, which are also without lymphovascular invasion and HER2/neu amplification, represented the group of cancers with a low probability of axillary lymph node metastases.