Real-world data indicate lower adherence rates for breast cancer endocrine therapy when radiation therapy is omitted

Many patients with early-stage breast cancer do not consistently maintain the long-term hormone therapy prescribed after lumpectomy, a large U.S. insurance claims analysis indicates. Findings provide important real-world context for treatment approaches that consider omitting radiation therapy, which typically rely on the expectation that patients will continue taking medication for at least five years.

Fewer than 30% of patients remained above a standard adherence threshold during all five recommended years of endocrine therapy. Patients who did not receive radiation therapy were more likely to experience substantial lapses in adherence than those who did, and younger age was also associated with lower adherence. Results will be presented today at the American Society for Radiation Oncology (ASTRO) Annual Meeting.

“Radiation therapy after lumpectomy has a well-established benefit in preventing breast cancer from returning in the treated breast. For some patients with lower-risk disease, radiation therapy may reasonably be omitted after an individualized discussion, but this approach assumes that patients will continue endocrine therapy for several years. Our findings suggest that maintaining endocrine therapy as prescribed, taking a daily medication for five years, is more challenging in routine practice than we often assume,” said Shannon Jiang, MD, lead study author and a radiation oncology resident physician at Washington University School of Medicine in St. Louis.

After lumpectomy, patients with hormone receptor-positive early-stage breast cancer typically receive radiation therapy to reduce the risk of recurrence in the treated breast and endocrine therapy to lower the risk of the cancer returning overall. For selected older patients with lower-risk disease, clinical trials have shown that radiation therapy can be omitted without compromising overall survival, although the risk of local recurrence is higher. In those trials, endocrine therapy was part of the treatment plan for all patients, making long-term medication an important component of the radiation-omission strategy.

Endocrine therapy blocks or lowers the hormones that can fuel hormone receptor-positive breast cancer. Side effects such as hot flashes, fatigue, joint pain, effects on bone health and changes in memory and concentration, can make it difficult for some patients to continue treatment over several years, however.

“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,” Dr. Jiang said. “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.”

For the study, researchers analyzed Merative MarketScan commercial and multistate Medicaid claims data from 17,025 patients age 23 to 64 with hormone receptor-positive, early-stage breast cancer. All patients underwent lumpectomy and filled at least one endocrine therapy prescription, and 89% also received radiation therapy.

Researchers used pharmacy claims to calculate patients’ medication possession ratio, a measure of how consistently they filled endocrine therapy prescriptions. This measure cannot confirm that a person took each dose, but it indicates whether they had enough medication available to follow the prescribed treatment.

The standard definition classified patients as adherent when they had medication available for at least 80% of the measured period. Researchers also examined less stringent thresholds of 70%, 60% and 50% possession to identify increasingly substantial gaps in medication availability.

Overall, approximately 28% of patients remained continuously adherent at the 80% threshold through five-year follow-up. Annual adherence appeared considerably higher, with 59% to 75% of patients meeting the threshold in individual years, but the longitudinal analysis showed a steady accumulation of patients falling below it over time.

Radiation therapy omission was associated with a higher risk of nonadherence to long-term endocrine therapy. Patients who did not receive radiation therapy were twice as likely to fall below the 50% medication-possession threshold over time and were significantly more likely to fall below the 60% and 70% benchmarks. The association was not significant at the standard 80% adherence threshold.

The study was not designed to explain why receiving radiation therapy was associated with better adherence, and the findings do not show that radiation therapy caused patients to stay on endocrine therapy. Differences between the groups’ health care access or treatment preferences may have contributed, as could more frequent contact with oncology teams during radiation treatment.

Younger age was also associated with nonadherence. Patients younger than 60 had a 20% to 25% higher risk of becoming nonadherent across the thresholds studied, a finding Dr. Jiang said may become increasingly relevant as researchers study radiation therapy omission in younger patients with favorable tumor characteristics.

“As studies expand radiation therapy omission to younger patients with favorable tumors, it becomes increasingly important to understand what happens with long-term adherence to endocrine therapy in real-world settings,” Dr. Jiang said.

Because the database did not include patients older than 64, the analysis cannot show whether adherence differs among the older patients who currently make up much of the population considered for radiation therapy omission. Dr. Jiang said the team plans to add Medicare data to examine adherence in this group.

“Our goal is to give clinicians better real-world information for treatment counseling,” she said. “The evidence we use to guide de-escalation needs to be considered alongside what happens to patients over the years that follow.”