L. Lindström (Stockholm, Sweden)
Karolinska InstituteAuthor Of 1 Presentation
- H. Dar (Stockholm, Sweden)
- A. Johansson (Stockholm, Sweden)
- A. Nordensköljd (Gothenburg, Sweden)
- A. Iftimi (Valencia, Spain)
- C. Yau (San Francisco, CA, United States of America)
- G. Perez-Tenorio (Linköping, Sweden)
- C. Benz (San Francisco, CA, United States of America)
- B. Nordenskjöld (Linköping, Sweden)
- O. Stål (Linköping, Sweden)
- L. Esserman (San Francisco, CA, United States of America)
- T. Fornander (Stockholm, Sweden)
- L. Lindström (Stockholm, Sweden)
6P - 25-year survival and benefit from tamoxifen therapy by the clinically used breast cancer markers in lymph node-negative and ER-positive/ HER2-negative breast cancer
Abstract
Background
The clinically used breast cancer markers are known to predict short-term survival, but whether these markers predict long-term (25-year) survival is unclear. We therefore aimed to determine whether the clinically used markers are long-term prognosticators and predictors of tamoxifen therapy benefit in patients with lymph node-negative and ER-positive/ HER2-negative breast cancer.
Methods
Secondary analysis of the Stockholm Tamoxifen (STO-3) trial conducted from 1976 to 1990, randomizing postmenopausal lymph node-negative breast cancer patients to receive adjuvant tamoxifen therapy versus no adjuvant therapy. Distant recurrence-free interval (DRFI) by the clinically used markers was assessed by Kaplan-Meier and multivariable Cox proportional hazards analysis. Recursive partitioning analysis was performed to evaluate which markers best predict long-term survival.
Results
A statistically significant difference in 25-year DRFI was seen by tumor size (Log-rank, P<0.001) and tumor grade (Log-rank, P=0.019), but not by PR and Ki-67 status. Patients with smaller tumor size (T1a/b Hazard ratio [HR], 0.31; 95% CI, 0.17-0.55; T1c HR, 0.58; 95% CI, 0.38-0.88), and tumor grade 1 had a significantly reduced long-term risk (Grade 1 HR, 0.48; 95% CI, 0.24-0.95), compared to patients with larger (T2) tumor size and grade 3 tumors, respectively. A significant tamoxifen therapy benefit was suggested for patients with larger tumor size (T1c HR, 0.53; 95% CI, 0.32-0.89; T2 HR, 0.34; 95% CI, 0.16-0.73), lower tumor grade (Grade 1 HR, 0.24; 95% CI, 0.07-0.82; Grade 2 HR, 0.50; 95% CI, 0.31-0.80), and PR-positivity (HR=0.38, 95% CI, 0.24-0.62). Recursive partitioning analysis selected tumor size as the most important characteristic to predict survival, followed by trial arm for patients with larger tumors.
Conclusions
Our findings suggest that tumor size followed by grade are significant 25-year prognosticators of DRFI outcome. Further, a significant 25-year benefit from tamoxifen therapy was seen in patients with larger tumor size, lower tumor grade and PR-positive tumors.
Clinical trial identification
The trial center for the STO-3 trial was the Regional Cancer Center Stockholm-Gotland, in Stockholm Sweden. However, the start of the Stockholm Tamoxifen trial (STO-3) in 1976 was well before trial registration started in Sweden, therefore information on trial number is not available.
Legal entity responsible for the study
The authors.
Funding
Swedish Research Council and Swedish Cancer Society.
Disclosure
All authors have declared no conflicts of interest.