Controversies in treatment selection for patients with equivocal ER and HER2 results.

Formally, the term "equivocal" should not be used when reporting results of the assessment of ER status, but controversies exist about the prognostic and predictive value of a low ER expression (i.e. 1-9% positive cells) in breast cancer (so called ER-poor tumors). Because of the rarity of these cases, prospective clinical trials have not been conducted (and are unlikely to be conducted in the future) to define the optimal treatment strategy for the small subset of patients with ER-poor breast cancer. Therefore, the only available data stem from retrospective subgroup analyses of randomized clinical trials or from clinical datasets of individual Institutions. The still unanswered question is whether these tumors are responsive to endocrine treatment, and what is the magnitude of the benefit of endocrine interventions for patients with ER-poor breast cancer. Since a potentially life-saving benefit from empirical adjuvant endocrine therapy cannot be excluded, the safest clinical approach may be to consider both adjuvant endocrine therapy and chemotherapy in this rare subset of patients. Testing for HER2 overexpression by immunohistochemistry or for gene amplification by in situ hybridization techniques may end up with equivocal results. Patients with equivocal HER2 status were not eligible for the pivotal clinical trials of adjuvant trastuzumab, and the possible benefit of HER2-targeted therapies for this subset of patients is unknown. The clinical results of the NSABP B47 clinical trial will eventually clarify if trastuzumab is effective, and what is the magnitude of its effect, in this patient population.