CD24 Expression and differential resistance to chemotherapy in triple-negative breast cancer

The HER-2/neu gene is a proto-oncogene that is amplified in 10-30% of breast cancers. New drugs for targeted therapy, such as Herceptin, are effective for patients with HER-2/neu-positive tumors, making it necessary to have a noncostly and accurate method to assess HER-2/neu status. We studied the correlation of findings made by fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) staining and the possibility of combining IHC and other clinicopathologic characteristics of breast tumors to predict FISH-determined HER-2/neu status. The clinicopathologic characteristics analyzed were the size of the tumor, p53, lymph-vascular invasion, estrogen/progesterone receptors (ER/PR), tumor grade, axillary lymph node status, and patient age. A total of 199 cases of invasive breast cancer studied at the UCLA Pathology Laboratory during 2003 were included in this study. Tumors with IHC 0, 1+, 2+, and 3+ scores were found to be FISH positive in 3.5%, 6.4%, 25.7%, and 81.5% of the respective groups. Our study showed a strong association between the FISH-negative and IHC scored 0 and 1+ tumors, suggesting that the FISH test may not be necessary in these cases (p<0.0001). Although the concordance between IHC 3+ and FISH positive is high, 18% of the patients with overexpression of HER-2/neu fail to show gene amplification by FISH. HER-2/neu positivity was found to be proportionally associated with increasing grade in infiltrating ductal carcinoma (p<0.0001). p53-positive tumors are more likely to be HER-2/neu amplified (p=0.0003). Tumors that are negative for ER/PR are also associated with HER-2/neu positivity by FISH (31.15%, p=0.0016). FISH-determined HER-2/neu status is not associated with histologic type, tumor size, nodal status, lymph-vascular invasion, or patient age.

BACKGROUND: Physical examination (PE), mammography (MG), breast magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (PET), and pathologic evaluation are used to assess primary breast cancer. To the authors' knowledge, their accuracy has not been well studied in patients receiving neoadjuvant chemotherapy. Accuracies of each modality in tumor and lymph node assessment in patients with T3/T4 tumors receiving neoadjuvant chemotherapy were compared.METHODS: Forty‐five patients of a prospective clinical trial studying T3‐T4M0 tumors were included. Patients received neoadjuvant chemotherapy: docetaxel/carboplatin with or without trastuzumab before and/or after surgery (depending on HER‐2/neu status and randomization). Tumor measurements by PE, MG, and MRI and lymph node status by PE and PET were obtained before and after neoadjuvant chemotherapy. Concordance among different clinical measurements was assessed and compared with the tumor and lymph node staging by pathology. Spearman correlation (r) and root mean square error (RMSE) were used to measure the accuracy of measurements among all modalities and between modalities and pathologic tumor size.RESULTS: Compared with the tumor size measured by PE, MRI was more accurate than MG at baseline (r = 0.559, RMSE = 35.4% vs r = 0.046, RMSE = 66.1%). After neoadjuvant chemotherapy, PE correlated better with pathology than MG or MRI (r = 0.655, RMSE = 88.6% vs r = 0.146, RMSE = 147.1% and r = 0.364, RMSE = 92.6%). Axillary lymph node assessment after neoadjuvant chemotherapy demonstrated high specificity but low sensitivity by PET and PE.CONCLUSIONS: Findings suggested that MRI was a more accurate imaging study at baseline for T3/T4 tumor, and PE correlated best with pathology finding. PET and PE both correctly predicted positive axillary lymph nodes but not negative lymph nodes. Cancer 2009. © 2009 American Cancer Society.