Hypofractionated Partial Breast Irradiation in Treating Patients With Early Stage Breast Cancer

Will evaluate whether or not the risk of this outcome is higher than the risk of grade 2+ toxic events in the best performing arm of our prior clinical trial that evaluated dosing schedules of whole breast irradiation (2010-0559).

Patient-reported cosmetic outcome, functional status, and breast pain will be measured using the Breast Cancer Treatment Outcomes Scale (BCTOS) and will be compared for the IMPORT Low versus OPAL regimens. Each outcome will be evaluated both as a continuous variable and as a dichotomous variable with a cutpoint of >= 2.5, indicating a moderate or greater average change in the treated breast compared to the untreated breast which serves as an internal control. Will use descriptive statistics to summarize patient-reported cosmetic outcome, functional status, and breast pain over time. Box plots and graphical measures will be used to display the distribution of these outcomes over time and by treatment arm. Will conduct linear mixed models to assess changes in patient-reported cosmetic outcome, functional status, and breast pain scores over time. A random intercept will be included to account for within-subject correlations.

Physician-reported cosmetic outcome, functional status, and breast pain will be measured using the Breast Cancer Treatment Outcomes Scale (BCTOS) and will be compared for the IMPORT Low versus OPAL regimens. Each outcome will be evaluated both as a continuous variable and as a dichotomous variable with a cutpoint of >= 2.5, indicating a moderate or greater average change in the treated breast compared to the untreated breast which serves as an internal control. Will use descriptive statistics to summarize patient-reported cosmetic outcome, functional status, and breast pain over time. Box plots and graphical measures will be used to display the distribution of these outcomes over time and by treatment arm. Will conduct linear mixed models to assess changes in patient-reported cosmetic outcome, functional status, and breast pain scores over time. A random intercept will be included to account for within-subject correlations.

Will be estimated using Kaplan and Meier product-limit estimator and modeled with Cox proportional hazards regression. IBTR will be measured from the date of treatment initiation to the date of last evaluation or IBTR. The 5-year risk of IBTR and any recurrence will be estimated along with 95% confidence intervals. Differences in each of these outcomes by treatment arm will be assessed using the log-rank test. Cox proportional hazards regression and/or competing risks regression will be used if needed to account for imbalance among treatment arms with respect to risk factors for these outcomes.

Will be estimated using Kaplan and Meier product-limit estimator and modeled with Cox proportional hazards regression. Recurrence-free survival will be measured from the date of radiation treatment initiation to the earliest date of last clinic visit, date of first recurrence, or date of death. Differences in each of these outcomes by treatment arm will be assessed using the log-rank test. Cox proportional hazards regression and/or competing risks regression will be used if needed to account for imbalance among treatment arms with respect to risk factors for these outcomes.

Will be estimated using Kaplan and Meier product-limit estimator and modeled with Cox proportional hazards regression. DFS will be measured from date of treatment initiation to the earliest date of last clinic visit, date of progression, date of recurrence, date of metastasis, or date of death. Differences in each of these outcomes by treatment arm will be assessed using the log-rank test. Cox proportional hazards regression and/or competing risks regression will be used if needed to account for imbalance among treatment arms with respect to risk factors for these outcomes.

Will be estimated using Kaplan and Meier product-limit estimator and modeled with Cox proportional hazards regression. OS will be measured from the date of treatment initiation to the earliest date of last contact or death. Differences in each of these outcomes by treatment arm will be assessed using the log-rank test. Cox proportional hazards regression and/or competing risks regression will be used if needed to account for imbalance among treatment arms with respect to risk factors for these outcomes.

Assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4. Differences in National Cancer Institute CTCAE and Subjective, Objective, Management, Analytic (SOMA) toxicity by treatment arm will be evaluated using chi-square test or Fisher's exact test, as appropriate.

The trial will be considered feasible if >= 90% of enrolled and treated patients receive the prescribed radiation dosing per protocol without deviations.

For this analysis, the primary outcome is grade 2 or higher breast fibrosis measured using the Subjective, Objective, Management, Analytic/Late Effects Normal Tissue Task Force scale at the 3.5 year follow up visit. The exposure of interest is the presence of at least one copy of the C-509T allele in germline deoxyribonucleic acid (DNA). Will also conduct exploratory analyses to assess the association of TGF-beta genotype with cosmetic outcome, other PROs, and toxicities. T-test or rank-sum test will be used for continuous measures and chi-squared or Fishers exact test will be used for categorical measures.