Serum assessment detects nonadherence to adjuvant tamoxifen in early breast cancer

Serum assessment of drug level may detect early nonadherence to adjuvant tamoxifen therapy and identify patients with early breast cancer at risk of poorer outcomes, new data from the CANTO study have shown.

Researchers evaluated biochemical nonadherence to adjuvant tamoxifen therapy (based on tamoxifen serum level <60 ng/mL) at 1 year after prescription in 1,177 premenopausal women (median age, 45 years) with newly diagnosed early breast cancer enrolled in the prospective CANTO study. This identified “a worryingly high proportion of patients” – one in six or 16 percent (n=188) – who were nonadherent to adjuvant tamoxifen at only 1 year after treatment prescription, the researchers reported. [J Clin Oncol 2020;38:2762-2772]

Of note, the biochemical nonadherence rate was higher than the patients’ self-reported nonadherence rate of 12.3 percent (n=145). Among the 188 patients with biochemical nonadherence, 55.3 percent (n=104) self-reported adherence to adjuvant tamoxifen therapy.

Factors associated with biochemical nonadherence included not living with a partner as a couple (adjusted odds ratio [aOR] vs with a partner, 1.72; 95 percent confidence interval [CI], 1.02 to 2.89), a higher number of comorbidities (Charlson comorbidity score ≥1 vs 0: aOR, 1.85; 95 percent CI, 1.09 to 3.15), not receiving treatment with (neo)adjuvant chemotherapy (aOR vs those who received chemotherapy, 1.74; 95 percent CI, 1.04 to 2.91), and symptoms after tamoxifen prescription (median time from prescription to assessment, 3.9 months), such as musculoskeletal symptoms (aOR, 1.58; 95 percent CI, 1.06 to 2.37) and severe fatigue (aOR, 1.65; 95 percent CI, 1.07 to 2.5).

“None of the patients with serum tamoxifen levels <60 ng/mL had been exposed to any drug that may interfere with tamoxifen serum levels,” the researchers noted.

More than half (n=78) of the patients who self-reported nonadherence did not provide a personal or medical reason for not taking adjuvant tamoxifen as prescribed, while 57 patients cited toxicity as a reason.

“After a median follow-up of 24.2 months since tamoxifen serum assessment, patients who were biochemically nonadherent were found to have significantly shorter distant disease-free survival [DDFS] [adjusted hazard ratio, 2.31; 95 percent CI, 1.05 to 5.06; p=0.036],” the researchers reported.

At 3 years, 89.5 percent of patients with biochemical nonadherence vs 95.4 percent of those in the adherent cohort were alive without distant recurrence.

“In premenopausal patients with hormone receptor–positive breast cancer, especially those younger than 40 years of age, nonadherence to adjuvant endocrine therapy seems to be a major issue, and evidence suggests poorer survival outcomes in this population compared with older patients, partly due to higher nonadherence rates,” the researchers wrote. [J Clin Oncol 2016;34:3308-3314]

However, nonadherence to adjuvant endocrine therapy for early breast cancer is often under-recognized partly due to the unavailability of a gold-standard method for its detection and challenges in incorporating adherence assessments into routine clinical practice, they explained. “Previous studies based on indirect methods suggested that rates of nonadherence to adjuvant endocrine therapy over 5 years range from 25 percent to 50 percent, and increase over time,” they pointed out. [J Clin Oncol 2003;21:6-2-606; J Clin Oncol 2010;28:4120-4128; N Engl J Med 1989;320:479-484; J Clin Oncol 2008;26:556-562]

“Our study suggests that therapeutic drug monitoring may be a useful method to promptly identify patients who do not take adjuvant tamoxifen as prescribed and are at risk of poorer outcomes. Targeted interventions facilitating treatment adherence are needed and have the potential to improve short-term breast cancer outcomes,” they concluded.