• Retrospective Swedish study of tumors from primary and relapse sites that revealed the following discordance: ER 32.4% (n = 459), PR 40.7% (n = 430) and HER2 14.5% (n = 104). Additional changes occurred throughout tumor progression.

Like many prior reports, this impressive initiative demonstrated that ER, PR and HER2 status is frequently discordant between the primary tumor and the site of metastatic disease. This phenomenon most commonly involves the loss of positivity, but the gain of a target has also been observed. In either case, the clinical implications of these changes are unclear, but patients who lost ER seemed to have shorter survival, suggesting perhaps a change in biology and/or less of a response to treatment. In current clinical practice it seems as though most clinicians obtain at least 1 biopsy, if possible, to document metastatic disease. However, although this study documented continued variation of markers during disease progression, the role of repeat biopsies is neither defined nor recommended. Furthermore, while patients whose disease becomes positive for ER or HER2 should clearly receive appropriate treatment, whether targeted therapy should be fully abandoned for patients losing positivity is not known.