Symptoms of Menopause Influence Tamoxifen Adherence Rates

Common menopausal symptoms such as nausea and headaches can be used as predictive tools for adherence to the aromatase inhibitor tamoxifen, according to an analysis of data from the International Breast Cancer Intervention Study (IBIS-1).

Women may initiate treatment cessation due to an incorrect belief that these symptoms are tamoxifen-related, according to the researchers.

Tamoxifen has been proven to reduce the risk for breast cancer in women with an increased risk for disease development; however, the drug’s efficacy is linked to therapy duration. Between 60% and 80% of women complete a full course of tamoxifen therapy, with severe adverse events given as the primary cause of discontinuation.

Samuel G Smith, PhD, postdoctoral fellow at Leeds Institute of Health Sciences (Leeds, UK), and colleagues analyzed long-term follow-up data from the UK arm of IBIS-1 to observe the role of menopausal symptoms on adherence. The study included data from 3897 women randomly assigned to a 20 mg per day course of tamoxifen (n = 1987) or placebo (n = 2000), with adherence rates measured by intervals of less than 4.5 years or 4.5 years or greater.

The effect of menopausal adverse events experienced within the first 6 months of treatment on overall and arm-specific adherence served as the study’s primary endpoint.

Of the entire cohort, 66.8% of women adhered to therapy for at least 4.5 years, although a significantly greater percentage of women assigned placebo remained adherent (placebo vs tamoxifen, 71.5% vs 62.1%; P < .001). The greatest drop-out rates occurred during the first 12 months of therapy, followed by a significant difference in therapy adherence by treatment arm for the duration of follow-up (P < .05).

“The higher rate of drop-out in the early months of the trial suggests early intervention may be an effective way to promote long-term adherence,” the researchers wrote.

The most commonly reported menopausal symptoms included hot flashes (31.5%) and gynecological symptoms, such as irregular bleeding or vaginal dryness/discharge (13.8%). Less frequent symptoms included headaches (7%) and nausea and vomiting (5%). However, higher rates of nonadherence were observed among women who reported nausea and vomiting (odds ratio [OR] = 1.82; 95% CI, 1.35-2.47) and headaches (OR = 1.41; 95% CI, 1.08-1.84) than among women who reported gynecological symptoms (OR = 1.18; 95% CI, 0.99-1.41) or hot flashes (OR = 1.1; 95% CI, 0.94-1.3).

The researchers found that nausea and vomiting significantly contributed to nonadherence in both the tamoxifen arm (OR = 1.84; 95% CI, 1.22-2.76) and placebo arm (OR = 1.82; 95% CI, 1.16-2.87). Headaches significantly predicted nonadherence in the placebo arm (OR = 1.7; 95% CI, 1.16-2.5), whereas gynecological symptoms only reached significance for nonadherence in the tamoxifen arm (OR = 1.3; 95% CI, 1.05-1.63). 

The majority of adverse events were mild to moderate in severity. There were a significant inverse relationship between increasing symptom severity and treatment nonadherence.

“It’s important to manage expectations and provide accurate information on the likelihood of experiencing specific side effects and how these differ from symptoms that women may experience anyway,” Dr Smith said. “The high drop-out rate observed in the early stages of the trial suggest that more support is needed to help women understand and manage side effects that may be linked to their treatment.”

“To ensure women experience the full benefit of preventive therapy, interventions are required to support the management of menopausal symptoms and to promote adherence,” the researchers concluded. —Cameron Kelsall