Assessing Predictors of Outcomes of Guidelines-Concordant Treatment in Women with Early Stage Breast Cancer Open Access
Liao, Albert (Spring 2018)
Abstract
Introduction:
Previous studies examining disparities in treatment guideline adherence in early-stage breast cancer have been limited by small study sample sizes, localized geography, unknown causal factors, and lack of diverse populations. To address these issues, we used the National Cancer Data Base to assess socioeconomic, clinical, and facility factors that impact treatment compliance with the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) guidelines.
Methods:
The NCDB file contains 2,246,280 patients diagnosed between January 1st, 2004 to December 31st, 2014. Chi-square tests were used to identify significant differences in rates of guidelines adherence over time for facility type, facility location, quartiles of income, education, insurance status, distance, and tumor staging. Logistic regression modeling was used to compute odds ratios for likelihood of guidelines adherence controlling for these factors. A backward multivariable Cox proportional hazard model was fit and an extended Kaplan-Meier curve plotted. Overall survival was measured in months from date of diagnosis to date of either death or last follow-up.
Results:
Multivariate models revealed decreased use of post-breast conserving surgery (BCS) radiation, chemotherapy, and immunotherapy for women ≥ 75; for lower-volume treatment centers; for patients without private insurance; for patients in the lowest income quartiles; for patients in the lowest education quartile; for patients with higher comorbidities; and for patients having unknown stage tumor. Treatment compliance led to overall mortality reductions for all treatments examined.
Conclusion:
Certain socioeconomic, clinical, and facility factors influence guideline-concordant care and subsequent outcomes for patients with early-stage breast cancer. Approaches to reducing disparities in breast cancer treatment have had mixed progress; this points to a need for tailored interventions to improve guideline compliance so that non-compliance can be prevented in at-risk populations. With the new emphasis on value-based care, it is important to address these discrepancies in treatment and thus enhance survival for all individuals through better adherence to guideline concordant therapy.
Table of Contents
Table of Contents
Introduction 10
Epidemiology 10
Breast Cancer Staging 12
Figure 1: TNM staging influences the overall AJCC early cancer staging. 15
Treatment 15
Surgery 16
Radiation 17
Chemotherapy 19
Targeted Immunotherapies 21
Why is Guideline Concordant Care Important? 21
Barriers to Guideline Concordant Care 23
Databases 26
Thesis Proposal 27
Methods 27
Data Source and Study Population 27
Study Variables 28
Statistical Analysis 28
Post-Breast Conserving Surgery Radiation 29
Post BCS RT from 2004 to 2013 30
Factors Associated with BCS RT Treatment 30
Impact of BCS RT on OS 31
Discussion 31
Post Breast Conserving Surgery Figures: 34
Figure 2: Selection Criteria for Post-Breast Conserving Surgery Radiation Therapy Study 34
Table 1: Descriptive Statistics for All Variable: Post-Breast Conserving Surgery Radiation 35
Table 2: Univariate Association with Study Cohort: Post Breast Conserving Surgery Radiation 38
Table 3: Multivariable Logistic Regression Model for Post Breast Conserving Surgery Compliance 43
Table 4: Univariate Association with Overall Survival: Post Breast Conserving Surgery Radiation 46
Table 5: Multivariable Cox Proportional Hazard Model for Overall Survival- Post Breast Conserving Surgery Radiation 50
Figure 3: Kaplan Meier Curve for Receipt of Post-Breast Conserving Surgery Radiation Therapy 52
Chemotherapy 53
Chemotherapy Receipt from 2010 - 2013 53
Factors Associated with Chemotherapy Receipt for HER2+/HR- Patient 54
Factors Associated with Chemotherapy Receipt for HER2-/HR+ Patient 55
Factors Associated with Chemotherapy Receipt for HER2+/HR+ Patient 56
Factors Associated with Chemotherapy Receipt for Triple Negative Patients 57
Impact of Chemotherapy on OS 58
Discussion 59
Chemotherapy Figures 63
Figure 4: Selection Criteria for Chemotherapy 63
Table 6: Base Characteristics and Unadjusted Outcomes between Eligible Patients with HER2+/HR- Chemotherapy 63
Table 7: Univariate Association with Chemotherapy HER2+/HR- Patients 66
Table 8: Multivariable Logistic Regression Model for HER2+/HR- Chemotherapy 70
Table 9: Univariate Association with Overall Survival for HER2+/HR- Chemotherapy 72
Table 10: Multivariable Cox Proportional Hazard Model for Overall Survival for HER2+/HR- Chemotherapy 76
Figure 5: Kaplan Meier Curve for HER2+/HR- Breast Cancer 78
Table 11: Descriptive Statistics for All Variables for HER2-/HR+ Chemotherapy 79
Table 12: Univariate Association with HER2-/HR+ Chemotherapy Receipt 82
Table 13: Multivariable Logistic Regression Model for HR+ Chemotherapy 86
Table 14: Univariate Association with Overall Survival for HER2+/HR- Chemotherapy 88
Table 15: Multivariate Cox Proportional Hazard Model for Overall Survival HER2-/HR+ Chemotherapy 92
Figure 6: Kaplan Meier Curve for HER2-/HR+ Breast Cancer 96
Table 16: Descriptive Statistics for All Variables HER2+/HR+ Chemotherapy 97
Table 17: Univariate Association of HER2+/HR+ Chemotherapy 100
Table 18: Multivariable Logistic Regression Model for HER2+/HR+ Chemotherapy 104
Table 19: Univariate Association with Overall Survival for HER2+/HR+ Chemotherapy 108
Table 20: Multivariable Cox Proportional Hazard Ratio for HER2+/HR+ Chemotherapy 112
Figure 7: Kaplan Meier Curve for HER2+/HR+ Breast Cancer 116
Table 21: Descriptive Statistics for All Variables- Triple Negative Chemotherapy 117
Table 22: Univariate Association with Study Cohort- Triple Negative Chemotherapy 120
Table 23: Multivariable Logistic Regression Model for Triple Negative Chemotherapy 124
Table 24: Univariate Association with Overall Survival – Triple Negative Chemotherapy 127
Table 25: Multivariate Cox Proportional Hazard Model for Overall Survival- Triple Negative Chemotherapy 131
Figure 8: Kaplan Meier Curve for Triple Negative Chemotherapy 134
Immunotherapy 135
Immunotherapy Receipt from 2010-2013 136
Univariate Factors Associated with Immunotherapy Underuse in HER2+/HR- Cancers 136
Univariate Factors Associated with Immunotherapy Underuse in HER2+/HR+ Cancers 136
Multivariate Factors Associated with Immunotherapy Underuse in HER2+ Cancers 137
Effectiveness of Immunotherapy Receipt when Recommended by Evidence-Based Guidelines 137
Immunotherapy Figures 138
Table 26: Descriptive Statistics for HER2+/HR- Immunotherapy 138
Table 27: Univariate Association with Study Cohort- HER2+/HR- Immunotherapy 141
Table 28: Baseline Characteristics for Study Cohort: HER2+/HR+ Breast Cancer 145
Table 29: Univariate Association with Study Cohort Immunotherapy- HER2+/HR+ 148
Table 30: Multivariate Logistic Association with Study Cohort: All HER+ Breast Cancer 152
Table 31: Univariate Association with Overall Survival: HER2+/HR- Immunotherapy 154
Table 32: Univariate Associate with Overall Survival: HER+/HR+ Immunotherapy 158
Table 33: Multivariable Cox Proportional Hazard HER2+/HR- Immunotherapy 162
Table 34: Multivariable Cox Proportional Hazard HER2+/HR+ Immunotherapy 164
Figure 9: Kaplan Meier Curve Analysis for HER2+ Breast Cancer 168
Discussion 169
Overall Conclusion 172
List of Figures 176
List of Tables 176
Bibliography 178
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