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: < 4, 4-8, >8-12, >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 >8 and 12 weeks:

 Number of Pts 10 yr OS(%) p-value 10 yr DFS(%) p-value 
<4 weeks 774 69.6 ref 60.9 ref 
4-8 weeks 2263 71.5 0.1351 64.7 0.1043 
>8-12 weeks 742 77.3 0.0002 72.6 0.0001 
>12 weeks 35 77.0 0.4531 73.9 0.2124 
 Number of Pts 10 yr OS(%) p-value 10 yr DFS(%) p-value 
<4 weeks 774 69.6 ref 60.9 ref 
4-8 weeks 2263 71.5 0.1351 64.7 0.1043 
>8-12 weeks 742 77.3 0.0002 72.6 0.0001 
>12 weeks 35 77.0 0.4531 73.9 0.2124 

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-value DFS p-value 
Time to Adjuvant   
<4 weeks ref ref 
4-8 weeks 0.7762 0.6764 
>8-12 weeks 0.4251 0.1396 
>12 weeks 0.6861 0.9312 
Age <0.0001 <0.0001 
BMI 0.0238 0.0298 
Menopause Status 0.0126 0.1226 
Performance Status 2 0.0256 0.1665 
Surgery Type <0.0001 <0.0001 
Pathological Stage 3 0.0037 0.0229 
Positive Nodal Status <0.0001 <0.0001 
ER Negative <0.0001 <0.0001 
Chemotherapy Regimen <0.0001 <0.0001 
 OS p-value DFS p-value 
Time to Adjuvant   
<4 weeks ref ref 
4-8 weeks 0.7762 0.6764 
>8-12 weeks 0.4251 0.1396 
>12 weeks 0.6861 0.9312 
Age <0.0001 <0.0001 
BMI 0.0238 0.0298 
Menopause Status 0.0126 0.1226 
Performance Status 2 0.0256 0.1665 
Surgery Type <0.0001 <0.0001 
Pathological Stage 3 0.0037 0.0229 
Positive Nodal Status <0.0001 <0.0001 
ER Negative <0.0001 <0.0001 
Chemotherapy Regimen <0.0001 <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.