Abstract S5-03: Menopausal symptoms as predictors of long-term adherence in the International breast cancer intervention study (IBIS-1)
Authors: Smith SG , Sestak I , Forbes J , Howell A , Cuzick JJ 
Published: March 2017

Tamoxifen reduces the risk of breast cancer among women at increased risk of the disease. The effectiveness of the drug is dependent on its appropriate use for the duration of therapy. Adherence for the full course of preventive therapy ranges from 60-80%. Early discontinuation is largely attributed to side-effects, but no studies have validated this using 5-year follow-up data. We assessed the role of menopausal side-effects on long-term adherence in the UK arm of the International Breast Cancer Intervention Study (IBIS-1).

In the IBIS-1 trial, 4279 women in the UK were randomised to placebo vs. tamoxifen (20mg/day). A total of 292 were excluded (breast cancer, death, or other cancer), leaving 3987 to be included in the analysis (2000 placebo arm, 1987 tamoxifen arm). Adherence was calculated using data from six monthly clinical visits during the trial. Adherence (&lt;4.5 years, ≥4.5 years) was calculated using the Kaplan-Meier estimator. Our main objective was to investigate the effect of menopausal side effects experienced during the first six months on adherence overall and by treatment arm. All analyses were adjusted for age, Tyrer-Cuzick risk, smoking, hormone replacement therapy use, menopausal status, baseline symptoms, and treatment.

Overall, 66.8% of women were adherent for at least 4.5 years (placebo: 71.5% vs. tamoxifen: 62.1%, p&lt;0.001). Highest drop-out rates were found within the first 12 months of follow-up, and a significant difference in adherence between treatment arms was observed thereafter (p&lt;0.05). A low number of women experienced nausea/vomiting (5.0%) and headaches (7.0%), while higher proportions reported gynaecological symptoms (irregular bleeding/vaginal dryness/vaginal discharge, 13.8%) and hot flushes (31.5%). Women reporting nausea/vomiting (OR=1.82 [95% CI, 1.35-2.47], p&lt;0.001) and headaches (OR=1.41 [1.08-1.84], p=0.01) were significantly more likely to be non-adherent at 4.5 years. Long-term adherence was not significantly affected for those who reported hot flushes (OR=1.10 [0.94-1.30], p=0.2) or gynaecological symptoms (OR=1.18 [0.99-1.41], p=0.07) compared with their counterparts. Nausea/vomiting was significantly associated with non-adherence in both the placebo (OR=1.82 [1.16-2.87], p=0.009) and tamoxifen (OR=1.84 [1.22-2.76], p=0.004) arms. Headaches were associated with non-adherence in the placebo arm (OR=1.70 [1.16-2.50], p=0.006), while gynaecological symptoms were only significant in the tamoxifen arm (OR=1.30 [1.05-1.63], p=0.02). The majority of side effects were of mild or moderate severity and we observed significant trends for lower adherence with increasing severity for all symptoms (p&lt;0.05 to &lt;0.001).

In the IBIS-I trial, we observed a significant effect of common menopausal symptoms on long-term adherence. These effects were largely similar between tamoxifen and placebo arms, suggesting women are attributing age-related menopausal symptoms to preventive therapy. 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 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.

Citation Format: Smith SG, Sestak I, Forbes J, Howell A, Cuzick JJ. Menopausal symptoms as predictors of long-term adherence in the International breast cancer intervention study (IBIS-1) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr S5-03.