Endocrine Therapy Adherence Affects Breast Cancer Disease-Free Survival

Nonadherence to endocrine therapy significantly reduces disease-free survival in postmenopausal breast cancer patients

medwireNews: Breast International Group (BIG) 1-98 trial findings demonstrate the adverse impact of poor adherence to tamoxifen or letrozole in early-stage, hormone receptor-positive breast cancer survivors.

Both early cessation of letrozole therapy and noncompliance with letrozole and/or tamoxifen – defined as failure to take more than 90% of prescribed doses per 6-month interval – significantly reduced disease-free survival (DFS), with multivariate adjusted hazard ratios of 1.45 and 1.61, respectively, the authors report in the Journal of Clinical Oncology.

Jacquie Chirgwin, from Maroondah Breast Clinic in Victoria, Australia, and co-authors say the finding that failure to complete at least 54 months of the 60-month course of endocrine therapy affected outcome is in line with earlier tamoxifen study findings but highlight the magnitude of their result.

“The results of this analysis also suggest that a reduction in compliance translates into a DFS disadvantage, and it is the first to show that breast cancer outcomes relate to daily tablet compliance”, they add.

The BIG 1-98 analysis included 6144 postmenopausal women who received at least one dose of a 5-year planned course of tamoxifen or letrozole or sequential treatment of the two agents beginning with tamoxifen or letrozole.

Women were less likely to persist with treatment if they were assigned to receive a sequential protocol, with 20.8% and 20.3% of tamoxifen–letrozole and letrozole–tamoxifen patients not reaching the 54-month threshold for completion, respectively, versus 16.9% and 17.6% of those given only tamoxifen or letrozole.

In all, 18.9% of patients ended treatment early for reasons other than death or disease progression, the majority (82.7%) of whom did so after a median of 19 months, citing adverse events. The most common side effect leading to cessation of letrozole was arthralgia (33.0%), while thromboembolic complications were the most common in tamoxifen users (19.0%).

Other factors associated with early cessation of treatment included older age, smoking habits, node-negative status and a history of thromboembolism, the team adds.

“These results reinforce the importance of optimizing adherence by educating and supporting patients about the prognostic importance of adherence, the possible [adverse events] associated with switching treatment, and effective toxicity management”, Jacquie Chirgwin et al write.

Dawn Hershman, from Columbia University Medical Center in New York, USA, discusses the multifactorial nature of nonadherence in an accompanying editorial and suggests that physicians should be alert for patients given sequential therapy who may be especially vulnerable for nonadherence.

“Despite the mounting evidence that increased duration of adjuvant hormonal therapy improves outcomes and the dramatic improvements that have been made in the treatment of breast cancer, we can feel humbled by the growing evidence that noncompliance and early discontinuation are common and have an impact on disease-free survival”, she writes.

“Practitioners should be aware of this issue and intervene when possible. Most importantly, interventions to improve adherence and public policy to implement these interventions are needed to continue to improve breast cancer survival globally.”


Chirgwin JH, Giobbie-Hurder A, Coates AS, et al. Treatment adherence and its impact on disease-free survival in the Breast International Group 1-98 trial of tamoxifen and letrozole, alone and in sequence. J Clin Oncol 2016; Advance online publication 23 May. doi: 10.1200/JCO.2015.63.8619

Hershman DL. Sticking to it: Improving outcomes by increasing adherence. J Clin Oncol 2016; Advance online publication 23 May. doi: 10.1200/JCO.2016.67.7336

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