Serum Detection of Nonadherence to Adjuvant Tamoxifen and Breast Cancer Recurrence Risk

Abstract

PURPOSE Nonadherence to long-term treatments is often under-recognized by physicians and there is no gold standard for its assessment. In breast cancer, nonadherence to tamoxifen therapy after surgery constitutes a major obstacle to optimal outcomes. We sought to evaluate the rate of biochemical nonadherence to adjuvant tamoxifen using serum assessment and to examine its effects on short-term, distant disease-free survival (DDFS). PATIENTS AND METHODS We studied 1,177 premenopausal women enrolled in a large prospective study (CANTO/NCT01993498). Definition of biochemical nonadherence was based on a tamoxifen serum level < 60 ng/mL, assessed 1 year after prescription. Self-reported nonadherence to tamoxifen therapy was collected at the same time through semistructured interviews. Survival analyses were conducted using an inverse probability weighted Cox proportional hazards model, using a propensity score based on age, staging, surgery, chemotherapy, and center size. RESULTS Serum assessment of tamoxifen identified 16.0% of patients (n = 188) below the set adherence threshold. Patient-reported rate of nonadherence was lower (12.3%). Of 188 patients who did not adhere to the tamoxifen prescription, 55% self-reported adherence to tamoxifen. After a median follow-up of 24.2 months since tamoxifen serum assessment, patients who were biochemically nonadherent had significantly shorter DDFS (for distant recurrence or death, adjusted hazard ratio, 2.31; 95% CI, 1.05 to 5.06; P = .036), with 89.5% of patients alive without distant recurrence at 3 years in the nonadherent cohort versus 95.4% in the adherent cohort. CONCLUSION Therapeutic drug monitoring may be a useful method to promptly identify patients who do not take adjuvant tamoxifen as prescribed and are at risk for poorer outcomes. Targeted interventions facilitating patient adherence are needed and have the potential to improve short-term breast cancer outcomes.

Therapeutic drug monitoring of oral targeted antineoplastic drugs

“…While body weight and age have a significant impact as well [86], CYP2D6 phenotype accounts for 18-43% of the observed IIV of 40-49% in endoxifen C SS [14]. Considering this, TDM of endoxifen might be promising to identify patients with sub-optimal target concentrations [87]. Because no toxic tamoxifen dose has been identified, dose increases up until 120 mg QD for patients with endoxifen C SS < 5.97 ng/ mL have been investigated and TDM has proven feasible [20, [88][89][90][91][92].…”

The Prognostic Impact of Age at Diagnosis Upon Breast Cancer of Different Immunohistochemical Subtypes: A Surveillance, Epidemiology, and End Results (SEER) Population-Based Analysis

“…A lower incidence and shorter duration of chemotherapy-induced amenorrhea is reported in younger patients and may result in a worse prognosis for hormone receptor-positive breast cancer ( 29 – 31 ). Younger age is also reported to be a predictor of decreased adherence to adjuvant endocrine therapy, associated with increased mortality ( 32 – 34 ). Hershman et al ( 32 ) reported that women <40 years were 40% more likely to be non-adherent to their endocrine treatment than patients aged 50–65 years old ( p < 0.001).…”

Chronic Plasma Exposure to Kinase Inhibitors in Patients with Oncogene-Addicted Non-Small Cell Lung Cancer

“…This interaction is not relevant for crizotinib, dabrafenib, osimertinib, and trametinib [ 7 , 17 ]. Furthermore, in our study, data were collected retrospectively, making an objective evaluation of adherence impossible, which is one of the main causes of low-plasmatic exposure [ 9 , 18 ].…”