Discordant expression of hormone receptors and HER2 in breast cancer. A retrospective comparison of primary tumors with paired metachronous recurrences or metastases.

PURPOSE: Expression of biomarkers in breast cancer, such as the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), can impact therapeutic decisions; however, it has been reported that their expression may change with disease progression. The aim of this retrospective study was to investigate the expression of these biomarkers in primary breast cancer and in its metachronous recurrences or metastases, and to estimate the percentage of cases with discordant expression. METHODS: Paired primary and metastatic tumor samples were collected from patients with primary breast cancer and subsequent metachronous distant metastases, diagnosed at the Metaxa Cancer Hospital, Piraeus, Greece, from 1988 to 2008. Two cases of local recurrence were also included. ER, PR and HER2 expression were assessed by immunohistochemistry (IHC) according to ASCO-CAP 2007 guidelines. Statistical comparisons were made using McNemar's exact test and Bowker's test for symmetry. RESULTS: Tumor samples from 110 patients were analysed. In the primary tumor, ER, PR and HER2 were positively expressed in 64.5%, 58.2% and 32.7% of cases, respectively, and expression of these biomarkers was lost in 18.2%, 21.8% and 10.9% of the corresponding metastases, respectively. Overall, a change of ER, PR and HER2 expression from positive to negative and vice versa occurred in 27.3% (p = 0.0987), 25.5% (p < 0.001) and 18.2% (p = 0.5034) of the cases, respectively. CONCLUSION: The expression of ER, PR and HER2 in metachronous recurrences or metastases can be discordant from that observed in the primary tumor. As such changes can occur during disease progression, the evaluation of biomarkers in metastatic sites should be mandatory, whenever possible, to ensure that patients are receiving the most effective treatment at all times.