Prognostic value HER-2/neu expression in T1 to T3 breast cancer with axillary lymph node metastasis

Objective

Studies on the association of HER-2/neu with the axillary lymph node metastasis are controversial. Amplification of the protein product of the HER-2/neu oncogene in primary breast cancer specimens is associated with an adverse prognosis.

Methods

From January 2000 to December 2008, 504 breast cancer patients were operated on at General Hospital 'Sveti Vracevi' in Bijeljina. We selected 253 (50.2%) patients with breast cancer who had metastases to axillary lymph nodes.

Results

Extracapsular extension (ECM) was found in 103 (40.7%) patients. The patients were identified and divided into two groups: the HER-2-positive group (38 patients) and the HER-2-negative group (65 patients). In the HER-2-positive group ECM was seen in 62.5% of patients, compared with 37.4% in the HER-2-negative group (P = 0.059). The total number of lymph nodes showing ECM were also significantly more in the HER-2-positive group (48 out of 81, 59.25%), versus 13 out of 60 (21.66%) in the HER-2-negative group (P < 0.001). With a median follow-up of 96 months, factors with independent prognostic value for disease-free survival by multivariate analysis included HER-2/neu overexpression with extracapsular extension (P < 0.005), pN category (P < 0.01), presence of lymphovascular invasion (P < 0.005), and ECM (P < 0.001). An independent negative prognostic effect on overall survival was observed for HER-2/neu overexpression with extracapsular extension (P < 0.05), pN category (P < 0.05), and presence of lymphovascular invasion (P < 0.005) and ECM (P < 0.001).

Conclusion

In patients whose tumors expressed HER-2/neu who had positive lymph nodes and extracapsular extension, prognosis was significantly worse compared with those who were HER-2/neu-negative and lymph node-positive with extracapsular extension. These findings have led to the conclusion that HER-2/neu overexpression is associated with a more aggressive subtype of cancer.