Poor social and physical well-being, as well as comorbid depression, are modifiable risk factors for nonadherence to endocrine therapy (ET) for women who underwent breast cancer treatment, according to a post-hoc analysis of the TAILORx study. These risk factors should be targets for early intervention, the study authors suggested.
“To our knowledge, results from this trial may be among the first to report on factors associated with early discontinuation among women who have received personalized information on their 21-gene Oncotype DX RS used to guide their treatment,” Betina Yanez, PhD, from the department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, and colleagues wrote in JAMA Oncology.
“Our findings, combined with previous findings in the literature on anxiety and early discontinuation of ET, suggest that while depression may be predictive of early discontinuation, fear of recurrence and symptoms of anxiety that are captured in the FACT emotional well-being subscale may differently predict early discontinuation of ET,” the researchers wrote, and noted that, while the Trial Assigning Individualized Options for Treatment (TAILORx) did not assess a history of anxiety at time of diagnosis, “additional research can further elucidate how comorbid anxiety and depression differentially predict early discontinuation of ET.”
Endocrine therapy is a mainstay of treatment for women with breast cancer, and the authors noted that it “has been associated with up to a 50% reduction in breast cancer recurrence, a reduction in contralateral breast cancer, and approximately 30% reduction in breast cancer mortality,” and it is usually recommended for five or more years. Despite these statistics, nonadherence to the therapy is common.
“In a retrospective analysis, nonadherence to tamoxifen was 52.2% and nonadherence to anastrozole was 47% after 3 years,” the study authors wrote. “These findings were confirmed in a systematic review of 29 studies of patients with breast cancer as well as additional studies.”
Given the nonadherence to ET, other research has focused on age, out-of-pocket cost, adverse events related to ET, and polypharmacy. As to the latter, the study authors pointed out that higher adherence was found in those who were taking fewer medications at study baseline.
“Class of concurrent non-ET medications may also be an important factor associated with adherence,” they added. “Lipid-lowering drugs and antihypertensive drugs have been associated with favorable adherence, and frequent use of opioid-containing analgesics, anxiolytics or antipsychotics, and antidepressants have been associated with lower odds of adherence.”
Yanez and colleagues took a deeper dive in nonadherence by looking to see if they could unearth modifiable risk factors associated with patients stopping ET across the course of ET treatment in the TAILORx trial, which was a randomized clinical trial conducted from April 7, 2006, to Oct. 6, 2010.
“All participants received a diagnosis of hormone receptor–positive, ERBB2-negative, axillary node–negative breast cancer and started ET within a year of study entry,” Yanez and colleagues wrote. “Analyses were conducted in the intent-to-treat population. Statistical analysis took place from Jan. 15, 2020, to April 6, 2021.”
In the post hoc analysis, participants were queried prior to ET initiation on health-related quality of life measures using the Functional Assessment of Chronic Illness Therapy (FACIT) measurement system, which measured fatigue and endocrine symptoms. They also used the Functional Assessment of Cancer Therapy (FACT) scale to assess “domains of physical well-being, functional well-being, emotional well-being, and social/family well-being.” They noted that higher scores on the scales were related to better cancer-related health related quality of life (HRQoL).
“Early discontinuation of ET was defined as discontinuation less than 4 years from initiation for reasons other than death or recurrence,” the study authors wrote.
There were 954 women with a mean (SD) age of 56.6 (8.9 years) included in the post hoc analysis. Of these, there were 106 cases of early termination of ET “for an overall 4-year nonadherence rate of 11.4% (95% CI, 9.5%-13.6%). In the initial sample size of 954 participants, there were 106 early termination events and 62 censored durations (i.e., off study while still receiving ET),” Yanez and colleagues wrote.
They also found that “receipt of chemoendocrine therapy (versus receipt of ET only; hazard ratio [HR], 0.57; 95% CI, 0.35-0.92; P=0.02) and age older than 40 years (versus 40 years; HR for 41-50 years, 0.39; 95% CI, 0.18-0.85; P=0.02; HR for 51-60 years, 0.28; 95% CI, 0.13-0.60; P=0.001; HR for 61-70 years, 0.40; 95% CI, 0.18-0.86; P=0.02; and HR for >70 years, 0.23; 95% CI, 0.07-0.77; P=0.02)” was predictive of a lower chance of early discontinuation of ET.
Conversely, they found that, after adjusting for receipt of chemotherapy and age, “worse physical well-being compared with better physical well-being (HR, 2.12; 95% CI, 1.30-3.45; P=0.002) and worse social well-being compared with better social well-being (HR, 1.94; 95% CI, 1.20-3.13; P=0.006) were significantly associated with a higher probability of early discontinuation of ET.”
And, “[a]fter adjusting for receipt of chemotherapy (versus receipt of ET only) and age, a history of depression compared with no history of depression (HR, 1.82; 95% CI, 1.19-2.77; P=0.005) was the only medical comorbidity that was associated with early discontinuation of ET,” they noted.
Most notably, the following were individually and significantly associated with a higher risk of stopping ET:
- A history of depression compared with no history of depression (HR, 1.82; 95% CI, 1.19-2.77; P=.005), worse physical well-being compared with better physical well-being (HR, 2.12; 95% CI, 1.30-3.45; P=.002).
- Worse social well-being compared with better social well-being (HR, 1.94; 95% CI, 1.20-3.13; P=.006).
They did not find that the use of non-ET medications at study baseline was associated with ET discontinuation, but antidepressant use at baseline compared with non-use was associated with early discontinuation (HR, 1.87; 95% CI, 1.23-2.84; P=0.003).
“Findings from our study suggest that beyond age and treatment, modifiable factors such as poor social well-being, physical well-being, and comorbid depression are risk factors for early discontinuation of ET and may be important targets for future interventions that seek to improve ET adherence,” Yanez and colleagues wrote. “More specifically, our findings suggest that oncology clinicians should consider referral for psychosocial care or physical rehabilitation for patients at risk for early discontinuation of ET.”
Limitations of the study included that the reasons for discontinuation were not included; daily adherence information was not collected; and the study was limited in racial/ethnic heterogeneity, and therefore the findings may not be generalizable.
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Poor social and physical well-being, as well as comorbid depression, are modifiable risk factors for nonadherence to endocrine therapy (ET) for women who underwent breast cancer treatment, according to a post-hoc analysis of the TAILORx study.
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These risk factors should be targets for early intervention, according to the study authors.
Candace Hoffmann, Managing Editor, BreakingMED™
Yanez reported receiving grants from Northwestern University during the conduct of the study and consulting income from Blue Note Therapeutics outside the submitted work.
Cat ID: 22
Topic ID: 78,22,730,22,691,192,925
