Endocrine Therapy Outcomes In Senior Breast Cancer Patients
Overview
This study investigated the management of early-stage, hormone receptor-positive, and human epidermal growth factor receptor 2 negative (HR+/HER2−) breast cancer in older women aged 70 to 90 years between 2010 and 2015. Specifically, it focused on patients who underwent lumpectomy and omitted radiation therapy. The primary concern was whether these patients initiated endocrine therapy and the impact of endocrine therapy on their survival.
Out of the 2,618 patients studied, a significant portion, 30.9%, did not receive endocrine therapy. The analysis revealed that more recent years (2013–2015) were associated with a higher likelihood of endocrine therapy initiation, indicating an improvement in recent practices. Conversely, older patients (aged 81–90) were less likely to receive endocrine therapy.
The study’s survival analysis using Kaplan–Meier estimation and a Cox proportional hazard model with inverse probability weighting demonstrated that patients who received endocrine therapy had better overall survival outcomes. This suggests that endocrine therapy is beneficial for patients who omitted radiation therapy. While there has been progress in endocrine therapy initiation in recent years, some patient groups, particularly older individuals, remained less likely to receive this essential treatment.
This population-based study underscores the importance of endocrine therapy in the management of HR+/HER2− breast cancer, especially in cases where radiation therapy is omitted. It highlights the need for continued efforts to ensure that all eligible patients, including older individuals, receive appropriate endocrine therapy for improved survival outcomes.
Introduction
This study addresses critical gaps in understanding the management of older patients with early-stage hormone-receptor-positive breast cancer who have undergone breast-conserving surgery. Specifically, it focuses on the omission of radiation therapy following surgery, the utilization patterns of adjuvant endocrine therapy in this patient group, and the impact of these treatment decisions on survival outcomes.
Existing evidence from randomized trials and guidelines suggests that older patients with this type of breast cancer may be candidates for omitting radiation therapy, relying solely on adjuvant endocrine therapy post-lumpectomy. However, observational studies have revealed a shift in treatment patterns among these patients, with a growing number opting for endocrine therapy alone, particularly after 2012. Many of these studies are institution-based, potentially limiting their generalizability due to smaller sample sizes and data predating 2012.
This study aims to fill three important knowledge gaps:
- Examining the utilization patterns of endocrine therapy among older breast cancer patients who have omitted radiation therapy.
- Investigating the impact of endocrine therapy on survival outcomes in cases where radiation therapy is not administered.
- Hypothesizing that a significant proportion of patients who forego radiation therapy may also omit endocrine therapy, potentially leading to negative effects on their survival outcomes.
By analyzing a large national database and focusing on patients with American Joint Committee on Cancer (AJCC) Stage I disease, this study seeks to provide valuable insights into treatment decisions and their consequences for older breast cancer patients.
Methods
This study utilized data from the Surveillance, Epidemiology, and End Results (SEER) registry linked with Medicare claims, providing comprehensive information on patient demographics, tumor characteristics, treatment utilization, and survival outcomes. The study aimed to investigate the utilization patterns of radiation therapy and endocrine therapy among older breast cancer patients and their impact on overall survival.
Inclusion Criteria
Patients included in this study met the following criteria:
– Age between 70 and 90 years.
– Newly diagnosed with American Joint Committee on Cancer (AJCC) Stage I female breast cancer.
– Hormone receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2−).
– Diagnosis made between 2010 and 2015, with available claims data until the end of 2016.
– Continuous enrollment in Medicare Parts A and B, without health maintenance organization (HMO) coverage, for 12 months prior to diagnosis through 12 months after diagnosis.
– Continuous enrollment in Medicare Part D for 6 months after lumpectomy to capture endocrine therapy utilization.
– Underwent lumpectomy as the initial treatment within 6 months of diagnosis, excluding patients who received mastectomy based on specific billing and procedure codes.
Exclusion Criteria
Patients were excluded from the study if they did not meet the above inclusion criteria or if they:
– Did not have continuous enrollment in Medicare Parts A and B without HMO coverage for the specified timeframe.
– Did not have continuous enrollment in Medicare Part D for 6 months after lumpectomy.
– Received mastectomy rather than lumpectomy as their initial treatment.
– Had missing or incomplete data relevant to the study variables.
Statistical Analysis
In this study, various statistical analyses were conducted to investigate the utilization patterns of endocrine therapy and its impact on overall survival among older breast cancer patients. The following key methods and statistical tests were employed:
Descriptive Statistics
The study provided descriptive statistics, including frequencies and percentages, stratified by the initiation of endocrine therapy.
Chi-squared Tests
Chi-squared tests were used to assess differences in the utilization of endocrine therapy among patient subgroups based on various characteristics.
Multivariable Logistic Regression
A multivariable logistic regression model was constructed, incorporating covariates with a Chi-squared p-value of less than 0.5 from prior bivariate analyses. This model aimed to identify factors associated with the initiation of endocrine therapy. Odds ratios (ORs), 95% confidence intervals (CIs), and p-values were reported for the logistic model parameters.
Kaplan–Meier Estimation
Overall survival was assessed using Kaplan–Meier estimation, which allowed for the evaluation of survival outcomes based on the use of endocrine therapy. The log-rank test was employed to compare survival curves between different groups.
Cox Proportional Hazards Regression
To account for potential confounding factors such as age, race and ethnicity, comorbidity, and other relevant variables affecting both endocrine therapy utilization and survival, a Cox proportional hazards regression was conducted. In this analysis, inverse probability weighting was employed to mitigate the impact of confounding variables on overall survival. Hazard ratios (HRs), 95% CIs, and p-values were reported for the Cox regression model.
Significance Levels
All statistical tests were two-sided, and p-values were reported. Significance levels (alpha) were set at 0.05, 0.01, and 0.001 for statistical tests. P-values were presented using an asterisk rating system, where ‘*’ indicated statistical significance with a p-value less than 0.05, ‘**’ indicated statistical significance with a p-value less than 0.01, and ‘***’ indicated highly statistical significance with a p-value less than 0.001.
Statistical Software
The statistical analyses were performed using SAS 9.4 (SAS Institute, Cary, NC).
Ethical Approval
It is important to note that all patient data used in the study were de-identified in the SEER-Medicare database, and the Institutional Review Board approved this retrospective observational study.
These rigorous statistical methods and tests were applied to comprehensively investigate the utilization of endocrine therapy and its impact on the survival outcomes of older breast cancer patients in a well-designed and ethically approved research study.
Results
The study focused on 2,618 patients aged 70 to 90 years diagnosed with AJCC Stage I breast cancer who underwent lumpectomy and omitted radiation therapy. Among these patients, 1,810 (69.1%) received endocrine therapy within six months after lumpectomy. Key findings from the study include:
Increase in Endocrine Therapy Uptake
The percentage of patients initiating endocrine therapy significantly increased from 62.6% in the years 2010–2012 to 72.2% in 2013–2015. This suggests an improving trend in the utilization of endocrine therapy over the study period.
Age Impact
Older patients (aged 81–90 years) had significantly lower odds of receiving endocrine therapy compared to those aged 70–80 years. The odds ratio (OR) was 0.45, indicating that older age was associated with a reduced likelihood of undergoing endocrine therapy.
Survival Outcomes
Kaplan–Meier survival curves and log-rank test results demonstrated that patients who received endocrine therapy had significantly better overall survival outcomes than those who did not receive it. The difference in survival was highly significant (p-value<0.0001).
Cox Proportional Hazard Model
A Cox proportional hazard model with inverse probability weighting was employed to adjust for potential confounding factors. The analysis confirmed that patients who underwent endocrine therapy had significantly better survival than those who did not, with a hazard ratio (HR) of 0.76 (95% CI: [0.58–0.99], p-value = 0.04). This further supported the positive impact of endocrine therapy on survival outcomes.
Year of Diagnosis
More recent years (2013–2015) were associated with improved survival outcomes compared to the earlier period (2010–2012). Patients diagnosed in the later years had a lower hazard of adverse outcomes (HR = 0.70, 95% CI: [0.49–0.98], p-value = 0.04).
Comorbidity and Age Effects
Older age (81–90 years) and higher comorbidity levels were associated with worse overall survival. The study found that older patients had a higher risk of adverse outcomes, with an HR of 2.30 (95% CI: [1.71–3.09], p-value<0.001). Similarly, higher comorbidity levels were linked to worse survival, with HRs of 1.98 (95% CI: [1.32–2.97], p-value = 0.001) and 3.11 (95% CI: [2.26–4.29], p-value<0.001) for moderate and severe comorbidities, respectively.
Marital and Urban/Rural Status
Marital status and urban/rural status were found to be associated with overall survival, indicating that these factors play a role in patients’ outcomes.
In summary, the study revealed an increasing trend in endocrine therapy utilization among older breast cancer patients who omitted radiation therapy. Patients who received endocrine therapy demonstrated significantly improved overall survival outcomes. Additionally, factors such as age, comorbidities, year of diagnosis, and demographic variables were associated with differences in endocrine therapy utilization and survival outcomes, emphasizing the importance of individualized treatment approaches in this patient population.
Conclusion
This comprehensive study investigated the initiation of endocrine therapy in older women with early-stage hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer who had undergone breast-conserving surgery without radiation therapy. The findings shed light on several crucial aspects:
Increasing Endocrine Therapy Utilization
The study revealed a noteworthy increase in the utilization of endocrine therapy among patients over time. The percentage of patients receiving endocrine therapy rose from 62.6% in those diagnosed between 2010 and 2012 to 72.2% in those diagnosed between 2013 and 2015. This trend indicates an improving awareness among clinicians regarding the importance of endocrine therapy, especially for patients who forgo radiation therapy.
Survival Outcomes
Analysis of overall survival demonstrated that patients who received endocrine therapy experienced significantly better survival outcomes compared to those who did not. This result offers robust evidence supporting existing guidelines that recommend endocrine therapy for older patients who forego radiation therapy.
Impact of Healthcare Policies
The study suggested that factors such as the Affordable Care Act (ACA), implemented in 2010, may have contributed to the improved uptake of endocrine therapy. The ACA has extended healthcare coverage to millions of Americans, including cancer patients, potentially facilitating access to standardized cancer care.
Challenges with Older Patients
The research also highlighted the challenges associated with older patients, particularly those aged over 80 years. Older age was associated with a reduced likelihood of endocrine therapy initiation, consistent with previous studies. Factors such as competing comorbidities and side effects of endocrine therapy, including headache, depression, and musculoskeletal symptoms, can pose challenges for physicians when managing treatment for older patients.
Strategies for Improvement
The study discussed various strategies that have been proposed to improve endocrine therapy initiation and reduce discontinuation, including patient navigation, culturally tailored approaches, smartphone app-based interventions, and patient decision aids. These strategies may be particularly relevant for older patients who omit radiation therapy.
Despite its valuable insights, the study has some limitations, including the lack of information on why certain patients did not receive endocrine therapy and the inability to assess long-term adherence to recommended endocrine therapy due to limited follow-up data. Additionally, the findings primarily apply to Medicare enrollees with specific insurance coverage, which may limit generalizability to other patient groups.
In summary, this nationwide observational study provides critical insights into the initiation of endocrine therapy and its impact on survival outcomes in older women with early-stage HR+/HER2- breast cancer who omit radiation therapy. It underscores the need to ensure that all eligible patients, especially older individuals, receive recommended endocrine therapy, emphasizing the potential for improved survival outcomes with appropriate treatment. Further research is warranted to explore strategies for enhancing endocrine therapy initiation and adherence in this patient population.
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