Abstract
BackgroundThe breast cancer microenvironment contributes to tumor progression and response to chemotherapy. Previously, we reported that increased stromal Type X collagen α1 (ColXα1) 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 ColXα1 and long-term outcome of ER+/HER2+ breast cancer patients in an adjuvant setting.MethodsA total of 164 cases with at least 5-year follow-up were included. Immunohistochemistry for ColXα1 was performed on whole tumor sections. Associations between ColXα1expression, clinical pathological features, and outcomes were analyzed.ResultsColXα1 expression was directly proportional to the amount of tumor associated stroma (p = 0.024) and inversely proportional to TILs. Increased ColXα1 was significantly associated with shorter disease free survival and overall survival by univariate analysis. In multivariate analysis, OS was lower in ColXα1 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 ColXα1 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 ColXα1 expression was associated with poorer prognosis.ConclusionColXα1 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 ColXα1 as a breast cancer associated stromal factor that predicts response to chemotherapy.
Highlights
The breast cancer microenvironment contributes to tumor progression and response to chemotherapy
We previously reported that increased stromal Type X collagen α1 (ColXα1) expression in estrogen receptor (ER)+/Human epidermal growth factor receptor 2 (HER2)+ tumors is associated with poor response to neoadjuvant therapy
In a multivariate cox proportional hazards analysis, overall survival (OS) was lower in ColXα1 expressing (HR = 2.1, 95% CI, 1.2 to 3.9) older patients (HR = 5.3, 95% CI, 1.7 to 17) with higher stage (HR = 2.6, 95% CI, 1.3 to 5.2) and low tumor infiltrating lymphocytes (TILs) (HR = 0.96; 95% CI, 0.9–1.0)
Summary
The breast cancer microenvironment contributes to tumor progression and response to chemotherapy. We reported that increased stromal Type X collagen α1 (ColXα1) and low TILs correlated with poor pathologic response to neoadjuvant therapy in estrogen receptor and HER2-positive (ER+/HER2+) breast cancer. We previously reported that increased stromal Type X collagen α1 (ColXα1) expression in ER+/HER2+ tumors is associated with poor response to neoadjuvant therapy. Our findings provided initial evidence that a specific stromal collagen subtype in the breast tumor microenvironment predicts therapy response [10]. Some studies have reported that tumor microenvironment components like tumor infiltrating lymphocytes (TILs) and tumor-associated stroma predict response to therapy and breast cancer progression [15]. In this study we aimed to evaluate the prognostic and predictive value of ColXα1 expression in the tumor stroma of ER+/HER2+ breast tumors in the adjuvant setting
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