Patients with early-stage, estrogen receptor-positive breast cancer who forgo radiotherapy after lumpectomy may be less likely to remain adherent to adjuvant endocrine therapy over five years, highlighting a potential challenge for treatment de-escalation strategies, show data presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting.
“Our findings are a reminder that doctors prescribing endocrine therapy for five years and patients actually taking the medication for five years are not the same thing,” said Shannon Jiang, MD, lead study author and a radiation oncology resident physician at Washington University School of Medicine in St. Louis. “When radiation therapy is omitted, endocrine therapy becomes an especially important part of the treatment strategy for preventing recurrence. We need to have realistic conversations with patients considering this approach about what long-term treatment and their quality of life will involve.”
Standard treatment for patients with early-stage breast cancer is lumpectomy followed by RT and five years of endocrine therapy to reduce the risk for recurrence. However, landmark trials have suggested that RT may be omitted in select older patients with favorable risk factors, but these trials assume that patients will use endocrine therapy as prescribed.
In reality, endocrine therapy can place substantial burden on patients’ lives, with common side effects including joint pain, hot flashes, fatigue, changes in sexual health, and changes in mood or cognition.
“For our patients, even moderate symptoms can be quite distressing, and these can lead to treatment interruptions or stopping treatment early,” said Jiang.
In order to understand how likely it is for patients to adhere to ET for five years post surgery, Jiang and team calculated medication possession ratios (MPR) from national insurance claims data for 17,025 women (median age 56 years) prescribed endocrine therapy for ER-positive early-stage breast cancer between 2006 and 2019. All patients underwent lumpectomy and 89% received adjuvant RT.
Jiang noted that the standard definition for medication adherence is an MPR of at least 80%, meaning that the patient has medication available for at least 80% of the measured period. In the current study, the researchers also looked at less stringent definitions of adherence, with MPR thresholds of 70%, 60%, and 50%.
They found that, across all MPR definitions, the proportion of patients who remain adherent decreases steadily with time.
At the gold-standard MPR cut-off of 80%, approximately 28% of patients remained adherent to endocrine therapy at five years. The proportion adherent was around 50% at an MPR threshold of 70%, increasing 75% adherence when the less stringent MPR threshold of 50% was used.
“Importantly, MPR really only tells us half the story,” said Jiang. “It tells us whether or not our patients are filling their prescriptions, but it does not tell us if our patients are actually taking the medication. So even this measure is likely overestimating adherence.”
Further analyses revealed that receipt of radiotherapy was associated with better adherence at lower MPR thresholds. For example, at an MPR of 50% or higher, patients who received RT were twice as likely to be adherent to endocrine therapy at five years as those who did not receive RT. Patients who received RT were also significantly more likely to be adherent at the 60% and 70% thresholds, but the association was not significant at the standard 80% adherence threshold.
Although the study was not designed to explain why receiving RT was associated with better adherence, Jiang suggested that the patients given RT might represent a group that’s already more engaged with the healthcare system. She added that having RT could create more opportunities for support through more frequent patient contact with their oncology team. The team might reinforce the importance of endocrine therapy or recognize and manage side effects earlier.
The investigators also found that age was independently associated with non-adherence: patients under 60 years were 20–25% more likely to be nonadherent across all MPR thresholds than older patients.
And when the researchers evaluated the interaction between receipt of RT and age, they found that even among younger patients at higher risk for becoming non-adherent, those who receive RT were more likely to stay on their endocrine therapy over time.
“This is particularly relevant as radiation omission strategies are increasingly being studied in younger patient cohorts,” said Jiang. “And so clinically, I think the main takeaway is that although radiation omission is an appropriate strategy for many of our patients, these treatment strategies should really be individualized.”
She added: “When we’re counseling our patients, we should be thinking, how realistic is it for our patients to stay on endocrine therapy for several years? And ultimately, as we continue to move towards treatment de-escalation, supporting our patients by assessing treatment tolerance early, revisiting adherence regularly, and offering supportive resources when needed will be really important in ensuring that these treatment strategies are successful.”
