Endothelial Cell pY397-FAK Expression Predicts the Risk of Breast Cancer Recurrences after Radiotherapy in the...

Area of Science:

• Oncology
• Biomarkers
• Radiotherapy

Background:

• Identifying biomarkers for radiotherapy (RT) response is crucial for optimizing early breast cancer treatment.
• Endothelial cell (EC) expression of phospho-Tyr397-FAK (pY397-FAK) is a potential predictive marker.

Purpose of the Study:

• To investigate the interaction between EC pY397-FAK expression and adjuvant RT on clinical outcomes after breast-conserving surgery (BCS).
• To determine if EC pY397-FAK can predict response to RT in early breast cancer patients.

Main Methods:

• Analysis of tissue microarrays from 1,178 early breast cancer patients in a randomized trial comparing BCS alone versus BCS plus RT.
• Immunohistochemical staining for pY397-FAK and other markers, with quantitative scoring of EC pY397-FAK intensity.
• Multivariable Cox regression analysis to assess the association between EC pY397-FAK, RT, and recurrence endpoints.

Main Results:

• EC pY397-FAK expression was not predictive for locoregional recurrence, but the RT effect aligned with preclinical data.
• A significant interaction between EC pY397-FAK and RT was observed for all recurrence (P = 0.026).
• Without RT, higher EC pY397-FAK was associated with a lower risk of all recurrence (HR = 0.74 per SD).

Conclusions:

• Patients with low EC pY397-FAK expression benefit more from RT within the first 5 years post-BCS.
• Low EC pY397-FAK expression without RT is linked to an increased risk of recurrence.
• EC pY397-FAK may serve as a predictive biomarker to personalize RT decisions in early breast cancer.