Lead Investigator: Youssef Zeidan, American University of Beirut Medical Center
Title of Proposal Research: Evaluation of Radiotherapy in Triple Negative Breast Cancer: Analysis of the BEATRICE trial
Vivli Data Request: 5931
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Radiotherapy has consistently shown to decrease the incidence of locoregional recurrence and frequently leads to increased survival in breast cancer. Locoregional recurrence is defined by the recurrence of cancer cells at the same site as the original tumour or at the regional lymph nodes after a disease free period. The greatest benefit has continuously been shown in larger tumors of favorable molecular subtypes and with increased nodal involvement. Favorable molecular subtypes are described as those with estrogen/progesterone receptor positivity that can be targeted by hormonal deprivation or receptor blocker therapy. HER2 positivity is the third receptor analyzed for which target monoclonal antibody therapy, trastuzumab, can be given. Administration of radiotherapy for triple negative breast cancer patients has been shown to improve outcomes of patients but in a few small-scale trials.Triple negative breast cancer is defined on molecular analysis of breast cancer cells showing absence or minimal expression of estrogen, progesterone, and Her-2 receptors for which targeted therapy is currently available. Radiation therapy remains to have well-known and numerous toxicities. It is crucial for radiation oncologists to balance the benefits and harms of radiation therapy. Further larger studies are still needed to analyze the effects of radiation therapy in patients with triple negative breast cancer. With the analysis of such a large database of TNBC patients, we are aiming at providing higher quality evidence (of higher power) for the effects of radiation therapy on this particular molecular subtype of breast cancer and provide a more definitive answer to whether radiation therapy is advised. That is until large scale RCTs are published on this patient population. This will lead to improved treatment for triple negative breast cancer patients.
Statistical Analysis Plan:
Power Calculation: The planned study is a secondary data analysis, which entails a predetermined sample size. Based on the published numbers in the primary study on this cohort, the estimated numbers of participants with PMRT in both treatments arms (with neoadjuvant Bevacizumab and without neoadjuvant Bevacizumab) is 952 and 953 patients, respectively. We estimated the LRR proportion in the no PMRT group to be 15% and 10% in the PMRT group. The number of patients exposed to PMRT are 1905 and unexposed group to be 686 patients. With an alpha of 0.05 and the estimated LRR frequency in both groups the power calculation yielded results greater than 80%. Univariate analyses will be conducted to describe the cohort. Categorical variables will be presented as frequencies and percent, and continuous variables as means and standard deviations (SD). Bivariate analyses will be used to compare characteristics as well as outcomes in frequencies and percent between exposed radiotherapy (+) and unexposed radiotherapy (-) groups, using the independent t-test (continuous variables) or the chi-square test (categorical variables). Multivariate regression analyses will be used to evaluate the association between radiation and LRR while adjusting for potentially confounding variables. Moreover, results will be presented as odds ratios (OR) with their associated 95% confidence intervals (95% CI). Factors considered for inclusion in the multivariate analyses will depend on the statistical significance of the bivariate analyses, as well as the clinical significance of different characteristics. Moreover, Kaplan Meier curves will be constructed to describe the time to recurrence in both radiation groups. Furthermore, to adjust for the confounding variables (which include, but are not limited to, age, size of primary tumor, nodal involvement, and metastasis, while considering time to recurrence as an outcome, Cox proportional hazards regression modeling will be used to estimate the Hazard Ratios (HR) with 95% CI. Assumption of proportionality will be demonstrated graphically on the Kaplan Meier curve with non-intersecting curves that do not fall off to 0. Another way to demonstrate it would be through the Schoenfeld residuals graph (which should roughly be flat). Statistical significance will be set at an alpha of 5% for a two-sided p-value. Analyses will be conducted using STATA.
An International Multi-centre Open-label 2-arm Phase III Trial of Adjuvant Bevacizumab in “Triple Negative” Breast Cancer.
Study ID: NCT000528567
Sponsor ID: BO20289
Kayali, M., Abi Jaoude, J., Mohammed, M. et al. Post-mastectomy Radiation Therapy in Triple-Negative Breast Cancer Patients: Analysis of the BEATRICE Trial. Ann Surg Oncol 29, 460–466 (2022). doi: 10.1245/s10434-021-10511-2