Thesis
The impact of radiotherapy on survival outcomes in triple negative breast cancer – data from the METABRIC cohort study
University of Iowa
Master of Science (MS), University of Iowa
Summer 2024
DOI: 10.25820/etd.007667
Abstract
Background: Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. This makes TNBC unsuitable for conventional hormone therapy. TNBC accounts for approximately 15% of all breast cancers and is associated with higher rates of recurrence and lower overall survival compared to other breast cancer subtypes. The standard treatment for early-stage TNBC includes chemoimmunotherapy, with pembrolizumab and chemotherapy showing promising results in the KEYNOTE-522 trial. However, the role of adjuvant radiotherapy in early-stage TNBC remains controversial.
Methods: We conducted a retrospective cohort study using data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). This study included 293 TNBC patients who underwent primary breast surgery, categorized into three groups: breast conserving treatment followed by radiotherapy (BCT+RT), postmastectomy radiotherapy (PMRT), and mastectomy only (MT only). We excluded patients who received BCT without radiotherapy. The primary outcomes were overall survival (OS) and relapse-free survival (RFS). Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI), adjusting for covariates such as age, molecular subtype, tumor laterality, cellularity, and tumor mutational burden.
Results: The final cohort comprised 293 TNBC patients, with 56.3% undergoing mastectomy. Patients who received PMRT had a significantly higher risk of death (HR: 2.747, 95% CI: 1.681-4.489) and recurrence (HR: 2.240, 95% CI: 1.44-3.485) compared to those who underwent BCT+RT. Age groups 30-69 were associated with a decreased risk of death. High tumor mutational burden was linked to better OS. The interaction effect between nodal status and surgery type with radiotherapy did not show significant influence on survival outcomes.
Conclusion: This study demonstrated that radiotherapy significantly improves survival in early-stage TNBC but offers less benefit for PMRT patients. Further, nodal status matters in treatment decisions for PMRT. We also conclude that other clinicopathological covariates such as age, Pam50/Claudin subtype, and tumor mutational burden play an important role in TNBC survival outcomes.
Details
- Title: Subtitle
- The impact of radiotherapy on survival outcomes in triple negative breast cancer – data from the METABRIC cohort study
- Creators
- Sruthi Sridhar
- Contributors
- Michael O'Rorke (Advisor)Priyanka Vakkalanka (Committee Member)Sarah Nash (Committee Member)Fabiola Kestelman (Committee Member)
- Resource Type
- Thesis
- Degree Awarded
- Master of Science (MS), University of Iowa
- Degree in
- Epidemiology
- Date degree season
- Summer 2024
- Publisher
- University of Iowa
- DOI
- 10.25820/etd.007667
- Number of pages
- x, 34 pages
- Copyright
- Copyright 2024 Sruthi Sridhar
- Language
- English
- Date submitted
- 07/23/2024
- Description illustrations
- Illustrations, tables, graphs, charts
- Description bibliographic
- Includes bibliographical references (pages 26-32).
- Public Abstract (ETD)
Background: Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer that lacks the receptors commonly targeted by hormone therapies. This makes TNBC difficult to treat and is associated with higher recurrence rates and lower survival compared to other breast cancer types. This study aimed to compare the effectiveness of different surgical and radiotherapy treatments on survival outcomes for TNBC patients.
Methods: We analyzed data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). We focused on 293 TNBC patients who underwent surgery. These patients were divided into three groups based on their treatment: breast conserving treatment followed by radiotherapy (BCT+RT), mastectomy followed by radiotherapy (PMRT), and mastectomy only (MT only). We examined overall survival (OS) and relapse-free survival (RFS), adjusting for factors such as age, tumor characteristics, and molecular subtypes.
Results: Our analysis revealed that patients who received BCT+RT had better OS and lower recurrence rates compared to those who underwent PMRT or MT only. Specifically, patients treated with PMRT had a higher risk of death and cancer recurrence. Age and certain molecular characteristics of the tumors also influenced survival outcomes.
Conclusion: This study finds that radiotherapy improves survival in early-stage TNBC but is less beneficial for postmastectomy patients. Nodal status is crucial in decision-making for PMRT treatment outcomes, along with factors like age, Pam50/Claudin subtype, and tumor mutational burden.
- Academic Unit
- Epidemiology
- Record Identifier
- 9984698249002771
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