Stromal ColXα1 expression correlates with tumor-infiltrating lymphocytes and predicts adjuvant therapy outcome in ER-positive/HER2-positive breast cancer

Background: The breast cancer microenvironment contributes to tumor progression and response to chemotherapy. Previously, we reported that increased stromal Type X collagen alpha 1 (ColX alpha 1) and low TILs correlated with poor pathologic response to neoadjuvant therapy in estrogen receptor and HER2-positive (ER+/HER2+) breast cancer. Here, we investigate the relationship of ColX alpha 1 and long-term outcome of ER+/HER2+ breast cancer patients in an adjuvant setting. Methods: A total of 164 cases with at least 5-year follow-up were included. Immunohistochemistry for ColX alpha 1 was performed on whole tumor sections. Associations between ColX alpha 1expression, clinical pathological features, and outcomes were analyzed. Results: ColX alpha 1 expression was directly proportional to the amount of tumor associated stroma (p = 0.024) and inversely proportional to TILs. Increased ColX alpha 1 was significantly associated with shorter disease free survival and overall survival by univariate analysis. In multivariate analysis, OS was lower in ColX alpha 1 expressing (HR = 2.1; 95% CI = 1.2-3.9) tumors of older patients (> = 58 years) (HR = 5.3; 95% CI = 1.7-17) with higher stage (HR = 2.6; 95% CI = 1.3-5.2). Similarly, DFS was lower in ColX alpha 1 expressing (HR = 1.8; 95% CI = 1.6-5.7) tumors of older patients (HR = 3.2; 95% CI = 1.3-7.8) with higher stage (HR = 2.7; 95% CI = 1.6-5.7) and low TILs. In low PR+ tumors, higher ColX alpha 1 expression was associated with poorer prognosis. Conclusion: ColX alpha 1 expression is associated with poor disease free survival and overall survival in ER+/HER2+ breast cancer. This study provides further support for the prognostic utility of ColX alpha 1 as a breast cancer associated stromal factor that predicts response to chemotherapy.