Measurements of serum levels of tamoxifen may be useful in monitoring adherence to adjuvant tamoxifen following surgery in premenopausal women with early-stage hormone receptor (HR)-positive breast cancer, according to results of a study published in the Journal of Clinical Oncology.

Long-term, oral endocrine therapy with agents such as tamoxifen or an aromatase inhibitor, with or without chemotherapy, is considered the standard-of-care for women with stage I to stage III, HR-positive, invasive breast cancer following primary treatment.

The risk of disease recurrence for these patients has been shown to be substantially reduced with 5 or more years of endocrine therapy; however, nonadherence has frequently been reported in this setting, particularly among premenopausal women. Although nonadherence to endocrine therapy represents a major obstacle to the achievement of optimal outcomes for these patients, the identification of patients who are nonadherent to such treatment remains challenging.

In this study (CANTO; ClinicalTrials.gov Identifier: NCT01993498), detailed data related to tumor and other biological characteristics; treatments and treatment-related toxicities; and clinical outcomes, including health-related patient-reported outcomes, were prospectively collected for women with newly diagnosed, early-stage breast cancer following primary treatment and then at 1, 3, and 5 years thereafter.


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This analysis is based on serum assessments of tamoxifen using a predefined cutoff of 60 ng/mL to separate biochemical adherence from biochemical nonadherence, as well as patient-reported adherence, at 1 year following prescription of adjuvant tamoxifen for the cohort of premenopausal patients who agreed to initiate such treatment following primary therapy.

Of the 1177 patients included in the analysis, 16% were determined to be biochemically nonadherent to adjuvant tamoxifen at 1-year. Although nonadherence was reported by 12.3% of patients at this time point, more than half of patients found to be biochemically nonadherent reported that they were adherent over the course of the year. Hence, although the 2 methods of adherence monitoring were found to be significantly associated (P <.001), they were only moderately concordant (86%).

On multivariable analysis, factors significantly associated with biochemical nonadherence included a higher level of comorbidities and not having a partner, as well as musculoskeletal symptoms and severe fatigue. In addition, not receiving neoadjuvant or adjuvant chemotherapy was also associated with a decreased level of biochemical adherence.

At a median follow-up of approximately 2 years, biochemically nonadherent patients had a shorter distant disease-free survival compared with biochemically adherent patients (hazard ratio [HR], 2.31; 95% CI, 1.05-5.06; P =.036). In addition, the 3-year rate of distant disease-free recurrence was 89.5% and 95.4% in the biochemically nonadherent and adherent groups, respectively.

The study authors noted that “this study adds to the understanding of the multifaceted and complex issue of nonadherence to chronic medications, suggesting that therapeutic drug monitoring may be an important tool to identify nonadherent patients who are at risk for a distant relapse event early in their adjuvant treatment trajectory.”

Reference

Pistilli B, Paci A, Ferreira AR, et al. Serum detection of nonadherence to adjuvant tamoxifen and breast cancer recurrence risk [published online June 22, 2020]. J Clin Oncol.  doi: 10.1200/JCO.19.01758