Participant-Reported Symptoms and Their Effect on Long-Term Adherence in the International Breast Cancer Intervention Study I (IBIS I)

Abstract

Purpose To assess the role of participant-reported symptoms on long-term adherence to preventive therapy in the United Kingdom sample of the International Breast Cancer Intervention Study (IBIS-I). IBIS-I was a randomized controlled trial that investigated the effectiveness of tamoxifen in reducing the risk of breast cancer among women at increased risk of the disease. Participants and Methods Women were randomly assigned to tamoxifen versus placebo (20 mg/day; n = 4,279). After 456 exclusions, 3,823 women were included in this analysis. Adherence (< 4.5 years or ≥ 4.5 years) was calculated using data from six monthly clinical visits. Analyses were adjusted for age, Tyrer-Cuzick risk, smoking, use of hormone replacement therapy, menopausal status, baseline menopausal symptoms, and treatment. Results Overall, 69.7% of women were adherent for at least 4.5 years (tamoxifen: 65.2% v placebo: 74.0%; P < .001). Differences in adherence between treatment arms were observed from 12 months onward (all P < .01) and were largest at 54 months. Dropout rates were highest in the first 12 to 18 months and decreased thereafter. Women reporting nausea/vomiting were less likely to be adherent in both the tamoxifen (odds ratio [OR], 0.57; 95% CI, 0.37 to 0.86; P = .007) and placebo (OR, 0.58; 95% CI, 0.37 to 0.93; P = .023) arms. Headaches were associated with adherence only in the placebo arm (OR, 0.62; 95% CI, 0.42 to 0.91; P = .016), whereas gynecologic symptoms were significant only in the tamoxifen arm (OR, 0.77; 95% CI, 0.62 to 0.97; P = .024). Effect sizes for each symptom on adherence were not significantly different between the treatment groups ( P > .05). In both treatment arms, we observed significant trends for lower adherence with increasing severity for all symptoms ( P < .01) except headaches ( P = .054). Conclusion In the IBIS-I trial, experiencing predefined symptoms in the first 6 months reduced long-term adherence. Effects were similar between treatment arms, suggesting that women were attributing age-related symptoms to preventive therapy. Interventions were required to support symptom management.

Fig 1.

CONSORT diagram for medication adherence analysis within International Breast Cancer Intervention I trial.

Fig 2.

Kaplan-Meier curve for adherence over 4.5 years of follow-up according to treatment arm.

Fig 3.

Annual hazard rates for nonadherence according to treatment arm.

Fig 4.

Adherence for 4.5 years according to severity of symptoms.