Identification of HER2-positive breast carcinomas as a particular subset with peculiar clinical behaviours

A large series of 2000 primary breast carcinomas was analyzed for HER2 overexpression, and its prognostic potential. A subset analysis, considering HER2-positive tumors as an independent subset of breast carcinomas, was conducted. In our series, HER2 positivity was not associated with nodal status, unless the number of infiltrated nodes was considered, whereas it was strongly associated with large tumors (P >10^-4), grade III tumors (P >10^-4), lymphoid infiltration (P >10^-4) and absence of hormone receptor expression (P >10^-4). HER2 overexpression was a strong prognostic indicator in N⁺patients (P <10^-7), whereas its prognostic impact was weak and not statistically significant in the N^- patients. Analysis of the hazard ratio of relapse in relation to time from surgery indicate that the poor prognosis associated with HER2-positivity in N⁺ patients was found to be due to a peak of relapses in the first 3-4 years from surgery. Multivariate analysis of different prognostic factors in HER2⁺ and HER2^- subsets indicated that grade is the most important factor, followed by nodal status, lymphoid infiltration and tumor size in HER2-negative breast carcinomas, whereas nodal status was the most important prognostic factor, with tumor size showing only borderline significance, in the HER2-positive group. Together, the results indicate that HER2-positive breast carcinomas represent a particular subset of tumors with peculiar clinical and pathological behaviours. Thus, conclusions drawn from clinical trials, which serve as the basis for clinical management of breast carcinomas, might not always be valid for this low-frequency subset.

Supported by AIRC.