Patients with breast cancer often stay on endocrine therapy for 5-10 years.
For many, however, long-term use is a challenge.
Stopping adjuvant endocrine therapy prematurely can have major consequences. These patients are more likely to experience cancer recurrence and to die earlier, research shows.
“Given that suboptimal adjuvant endocrine therapy adherence is common and is associated with breast cancer recurrence and mortality, there is a vital need for effective interventions to promote adherence,” Joanna J. Arch, PhD, from the University of Colorado Boulder, and colleagues write in a recent meta-analysis.
Experts discuss why it’s so challenging for patients to adhere to adjuvant endocrine therapy as well as which strategies may help boost long-term use and which likely will not.
The adherence problem
To improve adherence to adjuvant endocrine therapy, clinicians first need to understand the barriers patients face.
Studies indicate that a host of issues play into long-term adherence. Medication side effects, such as insomnia, fatigue, anxiety, depression, joint pain, and hot flashes, can deter patients from continuing endocrine therapy.
Tamoxifen, in particular, is known for its severe adverse events. Research suggests it may even increase patients’ risk for endometrial cancer and other uterine diseases.
Recent approvals of aromatase inhibitors – such as anastrozole, exemestane, and letrozole – have provided patients a tamoxifen alterative, but these agents come with their own issues, which include bone loss and vaginal dryness.
Common and severe side effects that affect adherence “should absolutely be addressed sooner, more frequently, and by any provider, not just the medical oncologist,” said Anna Weiss, MD, a breast cancer surgeon with the Wilmot Cancer Center, University of Rochester Medical Center, N.Y.
Other barriers to long-term use include the burden of managing comorbidities and drug costs as well as patients’ uncertainty about the value of long-term cancer therapy.
The issues that take center stage for individual patients may also vary by age. For older patients, comorbidities, cognitive function, and lack of social support may be key barriers to adherence, while for younger patients, fertility and sexual health issues are more pressing.
Clinicians should especially not underestimate the effects of hormonal suppression on adherence, explained Dr. Weiss, who recently published practice pearls on managing side effects of adjunctive endocrine therapy. “I do believe that we have been ignoring the sexual wellness aspect of breast cancer survivorship care for too long,” she said.
An array of fixes needed
Given the array of potential obstacles to endocrine therapy adherence, improving long-term use may be equally complex.
In a recent meta-analysis, Dr. Arch and colleagues combed the literature for studies exploring a host of strategies to improve endocrine therapy adherence. The team focused on 25 studies involving 367,873 women with breast cancer who were prescribed tamoxifen or an aromatase inhibitor.
The studies assessed a variety of interventions – disease management and exercise programs to lower side effects, medication reminders via phone or letter to limit missed doses, online educational materials to highlight the importance of adherence, as well as medication changes to reduce drug costs.
Overall, these interventions were of modest benefit in improving adherence. The findings indicate that “a variety of approaches” can be effective, Dr. Arch said.
But, she noted, aside from cost-cutting strategies, “no single approach stood out as more effective than others,” and some studies found minimal or inconsistent benefits to specific interventions.
One analysis, for instance, explored a text message intervention that involved sending patients several texts per week reminding them to take their medication, exercise more, or monitor their side effects. Overall, participants who received text messages missed fewer endocrine therapy doses, compared with those who didn’t – 7.1% versus 17.0% – and for about two-thirds of participants, the text messages motivated lifestyle changes.
Another study included in the meta-analysis, however, found that “twice-weekly text reminders did not improve adherence to aromatase inhibitors.”
Studies in which patients received educational materials about the importance of adherence or how to manage side effects found that effectiveness varied as well. Other analyses indicated that integrating relaxation techniques or other cognitive-behavioral approaches into patient care may have small beneficial effects on adherence.
Dr. Arch’s meta-analysis did, however, find a consistent benefit for cost-cutting interventions. Three large studies reported that medication adherence improved following policy changes that were focused on reducing costs of adjuvant endocrine therapy, either through legislation limiting out-of-pocket costs for oral drugs or by switching to generic formulations.
Xuanzi Qin, PhD, first author on one of the studies, explained that after generic aromatase inhibitor options became available, patients who switched to these options had lower out-of-pocket costs and higher rates of drug adherence.
The take-home message of the study is that “clinicians should know the out-of-pocket costs of the drugs and discuss the costs with patients,” Dr. Qin, of the University of Maryland School of Public Health, College Park, told this news organization.
Dr. Arch pointed out that although the meta-analysis found a consistent benefit to cost-cutting strategies, that does not necessarily translate to a strong benefit.
And overall, the body of research indicates that “we need to develop and test new strategies and hone existing ones,” Dr. Arch said, “so that we can boost adherence even more and help more women benefit fully from these life-extending medications.”
However, Dr. Weiss explained, seemingly small measures may still make important clinical differences for individual patients, even if studies don’t show a statistically significant impact overall on endocrine therapy adherence.
For Dr. Weiss, “even getting one patient to continue their endocrine therapy is a win in my book.”
Dr. Arch reported a consulting or advisory role with AbbVie/Genentech and Bristol-Meyers Squibb and research funding from NCCN/Astrazeneca. Dr. Weiss reports being on the advisory board for Merck and Myriad. Dr. Qin has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.