Abstract 2684: Telomere length of carcinoma-associated fibroblasts as a biomarker for breast cancer local recurrence

Abstract

Abstract The use of breast-conservative surgery (BCS) for the treatment of early-stage breast cancers has been increasing and the ability to identify patients at high risk of local recurrence is highly desirable for guiding treatment decisions. Currently, relatively few breast cancer local recurrent risk factors have been identified; those known risk factors, which are based on clinical and histological features of tumor tissue, have limited predictive power. It is known that molecular genetic changes often precede morphologic evidence of malignant transformation. Thus, early molecular genetic alterations in breast tumor and adjacent normal tissues are likely to be more sensitive tools for the identification of patients at increased risk of local recurrence than current histological criteria. A nested case-control study was carried out to evaluate whether telomere length in morphologically normal tissues adjacent to the tumor is predictive of breast cancer local recurrence. One hundred forty-two women who are diagnosed with breast cancer at Lombardi Comprehensive Cancer Center between 1998 and 2005 were included in the study. Cases (N = 42) are patients who had local recurrences of breast cancer after BCS. Controls (N = 100) are patient who had no local recurrence and are matched to cases on year of surgery, age at diagnosis, disease stage and type of surgery. Quantitative telomere fluorescent in situ hybridization (FISH) was used to determine the telomere length of four cell types: cancer cells, carcinoma-associated fibroblast cells (CAFs), adjacent normal epithelial cells and lymphocytes, using 5-micron sections of formalin fixed paraffin-embedded (FFPE) breast tumor tissues. Telomere length of lymphocytes was used to normalize the FISH hybridization variation and relative telomere length (RTL) was defined as telomere length in cells of interest divided by the telomere length of lymphocytes. Multivariate logistic regression was used to assess the association between RTL and breast cancer local recurrence. We found that mean RTL of CAFs was significantly longer in patients with breast cancer local recurrence (mean = 0.99) than in patients without local recurrence (mean = 0.74, p=0.022). When RTL of CAFs were dichotomized using median value of control subjects, patients who had longer RTL in CAFs had 2.4-fold (95% CI=0.86-6.56) increased risk of breast cancer local recurrence than women who had shorter RTL in CAFs. We observed no statistically significant case-control difference in mean RTL of normal epithelial cells adjacent to the tumor (p = 0.712) or in mean RTL of cancer cells (p = 0.285). This study is the first to report that telomere length in tumor stromal cells (CAFs) is associated with breast cancer local recurrence. If confirmed by future studies, telomere length in CAFs has the potential to become a novel molecular tool for the predicting breast cancer local recurrence. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2684.