Abstract P3-09-02: Association between definitive surgery and times to administration of adjuvant chemotherapy and outcomes in early breast cancer: Analysis of adjuvant studies conducted by NCIC Clinical Trials Group (NCIC CTG)
Authors: Ramjeesingh Ravi , Chen Bingshu E , Pater Joseph L , Zhu Liting , Burnell Margot , Bramwell Vivien H , Pritchard Kathleen I , Shepherd Lois E , Parulekar Wendy R 
Published: May 2015

Abstract
Background: For early high risk breast cancer, adjuvant chemotherapy following definitive surgery is a current standard of care. However, the optimal time to commencement of therapy has not been well established. We evaluated the association between time to initiation of adjuvant chemotherapy after definitive surgery (sTTC) with survival.
Methods: We retrospectively analyzed 4 NCIC CTG-led breast cancer adjuvant clinical trials involving women diagnosed from 1984 and 2005 with stage 1 to 3 breast cancer, who received adjuvant chemotherapy. Patient data were categorized into four time groups: &lt; 4, 4-8, &gt;8-12, &gt;12 weeks after definitive surgery. Outcomes measured were: overall survival (OS) and disease-free survival (DFS).
Results: 3837 patients were included in the final analysis. In univariate analysis, an improvement was identified for patients treated between &gt;8 and 12 weeks:
Number of Pts10 yr OS(%)p-value10 yr DFS(%)p-value&lt;4 weeks77469.6ref60.9ref4-8 weeks226371.50.135164.70.1043&gt;8-12 weeks74277.30.000272.60.0001&gt;12 weeks3577.00.453173.90.2124
However, in multivariate analysis there was no significant association between any sTTC time periods and either outcome (see table below). Covariates which did show a significant association are listed in the table.
OS p-valueDFS p-valueTime to Adjuvant &lt;4 weeksrefref 4-8 weeks0.77620.6764 &gt;8-12 weeks0.42510.1396 &gt;12 weeks0.68610.9312Age&lt;0.0001&lt;0.0001BMI0.02380.0298Menopause Status0.01260.1226Performance Status 20.02560.1665Surgery Type&lt;0.0001&lt;0.0001Pathological Stage 30.00370.0229Positive Nodal Status&lt;0.0001&lt;0.0001ER Negative&lt;0.0001&lt;0.0001Chemotherapy Regimen&lt;0.0001&lt;0.0001
The fact that the statistical significance of sTTC in univariate analysis was lost when covariates related to DFS and OS were accounted for in a multivariate analysis suggested there might be a relationship between sTTC and the risk of adverse outcomes. A disease risk score analysis was therefore carried out, but there was no indication of an advantage to an earlier sTTC within disease risk categories.
Conclusions: Within the context of chemotherapy given within 12 weeks, we were unable to demonstrate an effect on survival based on time to adjuvant chemotherapy in our multivariable analysis. Those treated later did not do significantly worse than those treated earlier. Significant covariates which effected survival were consistent with predictors of poor prognosis (younger age, poorer performance status, increased disease burden and receptor negativity). There is a potential relation of patient risk to time to treatment which requires further study.
Citation Format: Ravi Ramjeesingh, Bingshu E Chen, Joseph L Pater, Liting Zhu, Margot Burnell, Vivien H Bramwell, Kathleen I Pritchard, Lois E Shepherd, Wendy R Parulekar. Association between definitive surgery and times to administration of adjuvant chemotherapy and outcomes in early breast cancer: Analysis of adjuvant studies conducted by NCIC Clinical Trials Group (NCIC CTG) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-09-02.