Prospective Study Evaluating The Effect Of Impaired Tamoxifen Metabolisation On Efficacy In Breast Cancer Patients Receiving Tamoxifen In The Neo-Adjuvant Or Metastatic Setting.

523Background: Tamoxifen is commonly used to treat estrogen receptor (ER)-positive breast cancers, though the response to tamoxifen and its adverse event profile have a high degree of inter-individual variability. This might be attributable to the highly polymorphic CYP450 enzymes converting tamoxifen to more active metabolites and the patient’s genotype which modulates plasma levels. The clinical relevance of subtherapeutic endoxifen levels on clinical outcome, however, is controversial for a lack of data from prospective clinical studies. Methods: Postmenopausal women with ER-positive breast cancer starting tamoxifen as neo-adjuvant or first line metastatic treatment were included. The association between objective response rate (ORR) and steady state endoxifen levels was assessed. This was also evaluated for clinical benefit (CB) and progression-free survival (PFS). Tamoxifen and metabolite levels were assessed using high-performance liquid chromatography-tandem mass spectrometry. Additionally, we asse...