Serum assessment of non-adherence to adjuvant endocrine therapy (ET) among premenopausal patients in the prospective multicenter CANTO cohort

Abstract

Background: Previous studies demonstrated that younger patients (pts) with breast cancer (BC) are more likely to be non-adherent to adjuvant ET, leading to impaired prognosis. Methods: The CANTO cohort (NCT01993498) is a French multicenter prospective longitudinal study that will include 12000 pts with recently diagnosed stage I-III BC, to characterize long-term impact of BC treatment toxicities. CANTO COMPLETE, a pre-defined sub study, aims to determine, in premenopausal pts who have been prescribed adjuvant ET, the prevalence and dynamic predictors of non-adherence, at 1 (M12), 3 (M36) and 5 (M60) years, using serum assessment of tamoxifen (TAM) and aromatase-inhibitors (AI) matched with pts’ self-declaration. TAM dosage has been determined by liquid chromatography-tandem mass spectrometry on 200 µL of serum. According to standard definitions, adherence to TAM has been defined as: non-adherent if TAM ≤15 ng/mL (≤40 nM), poorly-adherent if TAM 15-60 ng/mL (40-150 nM) and adherent if > 60 ng/mL (>150 nM). Results: By December 2017, 11237 pts have been included in CANTO, of whom 1799 (16%) are premenopausal and have been prescribed and agreed to take ET: TAM 1496 (83.2%); TAM + LHRH-analogs (LHRH) 26 (1.4%); AI+LHRH 134 (7.5%); unknown 143 (7.9%).We present here the results of TAM plasma assessment at 1 year on all 1228 pts who reached 1 year of follow-up. Overall, 224 (18.2%) pts appeared not adequately adherent to TAM: 162 (13.2%) non-adherent and 62 (5.0%) poorly-adherent. Matching with pts’ self-declaration and clinical determinants of non-adherence will be presented. Conclusions: At one year from initiation of TAM, plasma measurements show that a substantial proportion of premenopausal pts are not adequately adherent to this treatment. Poorly-adherent pts could benefit from metabolic and pharmacogenetic investigations. Identification of pts at risk of non-adherence allows early targeted interventions to promote adherence in this unique population.