Prognostic and predictive impact of stroma cells defined by PDGFRb expression in early breast cancer: results from the randomized SweBCG91RT trial

Purpose Predictive biomarkers are needed to aid the individualization of radiotherapy (RT) in breast cancer. Cancer-associated fibroblasts have been implicated in tumor radioresistance and can be identified by platelet-derived growth factor receptor-beta (PDGFRb). This study aims to analyze how PDGFRb expression affects RT benefit in a large randomized RT trial. Methods PDGFRb was assessed by immunohistochemistry on tissue microarrays from 989 tumors of the SweBCG91RT trial, which enrolled lymph node-negative, stage I/IIA breast cancer patients randomized to RT after breast-conserving surgery. Outcomes were analyzed at 10 years for ipsilateral breast tumor recurrence (IBTR) and any recurrence and 15 years for breast cancer specific death (BCSD). Results PDGFRb expression correlated with estrogen receptor negativity and younger age. An increased risk for any recurrence was noted in univariable analysis for the medium (HR 1.58, CI 95% 1.11–2.23, p = 0.011) or PDGFRb high group (1.49, 1.06–2.10, p = 0.021) compared to the low group. No differences in IBTR or BCSD risk were detected. RT benefit regarding IBTR risk was significant in the PDGFRb low (0.29, 0.12–0.67, p = 0.004) and medium (0.31, 0.16–0.59, p < 0.001) groups but not the PDGFRb high group (0.64, 0.36–1.11, p = 0.110) in multivariable analysis. Likewise, risk reduction for any recurrence was less pronounced in the PDGFRb high group. No significant interaction between RT and PDGFRb-score could be detected. Conclusion A higher PDGFRb-score conferred an increased risk of any recurrence, which partly can be explained by its association with estrogen receptor negativity and young age. Reduced RT benefit was noted among patients with high PDGFRb, however without significant interaction.

Association of higher proliferation of Ki67 with unfavorable prognostic factors and shorter survival in breast cancer.

e11083 Background: The prognostic value of Ki67 expression level is yet unclear in breast cancer (BC). The aim of this study was to investigate the association between Ki67 expression levels and other prognostic factors in BC. Methods: Demographic, clinical and pathological features of the pts were retreived from the hospital records. Results: In this study, 163 pts with BC were analyzed. The mean age of the pts was 53.4±12.2 years. Median Ki67 level was 20% in this study. Ki67-high tumors were significantly associated with high grade (p<0.001), lymphovascular invasion (p=0.001), estrogen receptor negativity (ER-) (p=0.035), Her2 (+) (p=0.001), advanced stage (p<0.001) and lymph node involvement (LNI) (p<0.003) of the tumor. There was no relationship between the age, perineural invasion, progesterone receptor and Ki67 positivity. Lower Ki67 levels were significantly associated with longer median relaps-free survival (RFS) compared to those of higher Ki67 levels (p=0.008). The overall survival (OS) was longer in pts with lower Ki67 levels than those with higher levels (p=0.017). Conclusions: High Ki67 expression was associated with ER-, Her2 (+), higher grade and LNI in BC. The level of Ki67 expression was a prognostic factor predicting the RFS and OS in BC pts. [Table: see text]