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.

FIG 1.

CONSORT diagram of study participants. AI, aromatase inhibitor; ET, endocrine therapy; HR, hormone receptor; LHRH, luteinizing hormone-releasing hormone; TAM, tamoxifen.

FIG 2.

Multivariate estimates of variables associated with serum-defined adherence. Severe fatigue and insomnia were defined as the respective subscale European Organization for Research and Treatment of Cancer–C30 score > 40. Anxiety and depression were defined using the Hospital Anxiety and Depression Scale. BMI, body mass index; CT, chemotherapy; OR odds ratio.

FIG 3.

Distant disease-free survival (DDFS; distant recurrences and death) according to serum-defined adherence status in (A) the IPTW cohort and in the (B) non-IPTW cohort. Time 0 defines the time of the post-tamoxifen prescription visit and date of serum assessment of tamoxifen. HR, hazard ratio; IPTW, inverse probability treatment weighting.