The state of HER-2 status.

This editorial comments on the manuscript reported by Bergqvist et al. [1] who have investigated real-time PCR (RT-PCR) and microarray-based RNA expression (RNA-EP) as alternative strategies to immunohistochemistry (IHC) and in situ hybridization (ISH) for HER-2 testing in breast cancer patients. Bergqvist et al. [1] have compared the performance of ÔstandardÕ and ÔnewÕ HER-2 testing tools in a series of 250 primary breast tumors. Moreover, they have correlated clinical outcomes (relapse-free, breast cancer-related, and overall survival) with HER-2 scores evaluated by the investigated techniques. Bergqvist et al. [1] have to be congratulated for the significant amount of work that has been done and for exhaustively reporting the results of their study. This editorial will attempt to address two definite questions related to HER-2 testing: (i) in which clinical situation HER-2 testing results are of capital importance for patient's management? (ii) are new HER-2 testing technologies required to better assist clinicians in the decision-making process? There are four different clinical scenarios in which HER-2 testing results have or might have a role in the clinical management of breast cancer patients. The identification of patient candidates for anti-HER-2 therapies either in the early or in the metastatic setting is by far the most relevant information provided by HER-2 testing of breast cancer samples. Large phase III trials have unequivocally proved the efficacy of anti-HER-2 agents such as trastuzumab and lapatinib in patients carrying HER-2-positive tumors [2–7]. An emerging clinical situation in which HER-2 testing results can provide the clinician with meaningful information is represented by early breast cancer patients carrying hormone receptor and HER-2-positive tumors. In this setting, adjuvant hormonotherapy alone, either with antiestrogens or aromatase inhibitors, might not be the most appropriate treatment option. Preclinical and retrospective clinical studies indicate that these tumors might not be entirely sensitive to hormonal agents [8, 9]. In particular, early results from the trans-anastrazole or tamoxifen alone or in combination (TransATAC) study indicate that in the adjuvant setting HER-2 and hormone receptor-positive breast cancer tends to be less sensitive to both tamoxifen and aromatase inhibitors than HER-2-negative and hormone receptor-positive disease. The magnitude of anastrozole's superiority over tamoxifen seems to be independent of the primary tumor HER-2 status [9]. Of note, this recent finding contrasts the main conclusions from two previously reported neo-adjuvant studies indicating an increased superiority of aromatase inhibitors over tamoxifen in the presence of HER-2 and hormone receptor-positive disease [10, 11]. Of …