No abstract

Background: Breast cancer trial enrollment, while slightly higher than some other histologies, still remains low, at less than 4%. Research suggests lack of clinical trial participation is due to poor patient and clinician commitment and interest. Increasing incentive for trial participation may enhance engagement of patients and healthcare providers leading to increased patient enrollment. One incentive would be to understand benefits of trial participation with regards to better survival and outcomes. The purpose of this study is to determine differences in survival, overall and breast cancer specific, and surgical management, for women who participate in early breast cancer randomized clinical trials (RCT) compared to the general breast cancer population who received similar standard therapy outside of a RCT. Methods: Patients included in this retrospective analysis were from one of three (3) international, randomize, adjuvant breast cancer trials (RCT-participants) and women with breast cancer from the general U.S. population, from Surveillance Epidemiology and End Results Program (SEER-13), the controls. Women diagnosed between 1997-2004 with invasive breast cancer, tumor (T) size 1-3, lymph node (LN) positive (LN1/2), hormone receptor positive or negative, HER2 positive or negative, treated with surgery, adjuvant radiation, and chemotherapy were included in the analysis. In this study, propensity score analysis (PSA) was done to provide weight to each data point for each variable in order to more closely represent similar populations. PSA, considered superior to a standard Cox multivariate analysis as it attempts to reduce the bias due to confounding or correlated predictive variables. Subsequently, the propensity score was applied to a Cox proportional hazards model to determine hazard ratios (HR), with a Wald 95% confidence interval (CI), of trial participation on survival. Similarly, PSA was done for surgical outcomes. A multivariate logistic regression was performed to calculate the odds ratios, with a Wald 95% CI, to determine if RCT participation compared to the SEER-13 control had an impact on surgical outcomes, mastectomy versus breast conserving surgery (BCS). Results: The total sample size was 9255 patients, 1795 RCT-participants and 7460 SEER-13 controls. After controlling for all other significant predictors of survival, RCT participation significantly reduced risk of breast cancer related death at 5-years by more than 25% and 18% at 10 years [HR: 0.75 (95% CI: 0.64-0.87); p=0.00020; and HR: 0.83 (95% CI: 0.74-0.93); p=0.00165, respectively]. Additionally, we demonstrated a significant reduction in risk of all-cause mortality for RCT-participants, at both 5-years and 10-years [HR: 0.83 (95% CI: 0.72--0.95); p=0.009; and HR: 0.79 (95% CI: 0.71-0.87); p<0.00001, respectively]. Additionally, RCT-participants were significantly less likely to undergo invasive surgical management (mastectomy) compared to SEER-13 controls [OR: 0.78 (95% CI: 0.66-0.92;) p=0.03]. Conclusion: RCT-participants have a reduced risk of death at 5 years and 10 years compared to the general breast cancer population. Additionally, RCT-participants are less likely to undergo mastectomy than the SEER-13 controls. Citation Format: Brennan MB, Wiley D, Wang D, Wang X, Fasching P. The effect of participation in RCT on outcomes in patients with early breast cancer compared to the general breast cancer population [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-15-01.

Pathological complete response (pCR) has been shown to demonstrate improved outcomes in breast cancer. Often novel treatments, such as taxanes or HER2 based therapies, trastuzumab or pertuzumab, have shown an increase of pCR with possible impact on the prognosis of breast cancer patients. These therapies are usually introduced into the patient population through clinical trials. Therefore, it can be hypothesized participation in neoadjuvant clinical trials might improve the pCR rate in early breast cancer patients. The aim of this study was to explore this association. Methods: This is a retrospective study of consecutive breast cancer patients who were treated with a neoadjuvant chemotherapy at a single institution. Trial participation status was known for all patients. From 1995 to 2012 the institution participated in 10 different neoadjuvant chemotherapy trials. Outside those clinical trials, patients were treated according to national neoadjuvant therapy guidelines. Patients who took part in clinical trials were compared with patients who did not take part in clinical trials with appropriate univariate tests. Additionally, logistic regression was performed with pCR as the dependent variable and commonly known predictors of pCR (tumor size and molecular subtype) as independent variables. The model was adjusted for age at diagnosis, year of treatment and trial participation status. Furthermore, exploratory survival analyses were performed. Results: A total of 281 patients were treated within a neoadjuvant clinical trial and 822 patients outside a clinical trial. There are significant differences in the patient populations with regards to age (p=0.0009) and tumor size (<0.0001). pCR rate in patients with trial participation was 21.4% and 19.0% in patients who did not take part in clinical trials. Multivariate logistic regression showed an OR of 1.393 (95%CI 0.937-2.071, p=0.1012). Exploratory survival analyses showed a better prognosis in patients taking part in clinical trials. Conclusions: This study shows an increased chance of pCR in patients taking part in clinical trials; however the statistical test could not show statistical significance. Most likely the effect can be explained by trial participants having access to drugs which improved pCR rates, such as HER2 based therapies or taxanes. Citation Format: Brennan MB, Wang D, Gass P, Hein A, Beckmann MW, Fasching PA. The effect of participation in neoadjuvant clinical trials on outcomes in patients with early breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-16-18.