Abstract
PurposePredictive 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.MethodsPDGFRb 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).ResultsPDGFRb 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.ConclusionA 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.
Highlights
Radiotherapy (RT) in combination with breast conserving surgery (BCS) is currently the preferred treatment over mastectomy for patients with early stage breast cancer
A significantly increased risk was detected in univariable analysis for patients with a medium (HR 1.58, CI 95% 1.11–2.23, p = 0.011) or high platelet-derived growth factor receptorbeta (PDGFRb) score (HR 1.49, CI 95% 1.06–2.10, p = 0.021) as compared to the PDGFRb low score group (Fig. 4b, Table 2)
In a multivariable analysis including histological grade, age, RT and subtype, the significance remained for the PDGFRb medium (HR 1.46, CI 95% 1.01–2.11, p = 0.042) but not the PDGFRb high score group (HR 1.32, CI 95% 0.93–1.88, p = 0.125) (Table 2)
Summary
Radiotherapy (RT) in combination with breast conserving surgery (BCS) is currently the preferred treatment over mastectomy for patients with early stage breast cancer. Breast Cancer Research and Treatment (2021) 187:45–55 recurrences during the first decade after surgery [1, 2]. An increasing focus is being put on the microenvironment as a modulator of the benefit from adjuvant RT. A high number of tumor-infiltrating lymphocytes was shown to independently reduce the recurrence risk of early stage breast cancer patients within a randomized RT trial. Patients with low levels of tumor-infiltrating lymphocytes may represent a subgroup with an increased RT benefit [3]. Preclinical studies have indicated that stroma cells can modulate radiosensitivity of tumor cells [4,5,6,7], but non-leukocytic stroma cells have not yet been explored as potential predictive markers for benefit of RT in invasive breast cancer
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