Magnetic resonance imaging as a predictor of pathologic response in patients treated with neoadjuvant systemic treatment for operable breast cancer Translational Breast Cancer Research Consortium Trial 017
Department of Radiation Oncology, University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, Alabama. . Cancer
(Impact Factor: 4.89).
05/2013; 119(10). DOI: 10.1002/cncr.27995
Increased pathologic complete response (pCR) rates observed with neoadjuvant chemotherapy (NCT) for some subsets of patients with invasive breast cancer have prompted interest in whether patients who achieved a pCR can be identified preoperatively and potentially spared the morbidity of surgery. The objective of this multicenter, retrospective study was to estimate the accuracy of preoperative magnetic resonance imaging (MRI) in predicting a pCR in the breast.
MRI studies at baseline and after the completion of NCT plus data regarding pathologic response were collected retrospectively from 746 women who received treatment at 8 institutions between 2002 and 2011. Tumors were characterized by immunohistochemical phenotype into 4 categories based on receptor expression: hormone (estrogen and progesterone) receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative (n = 327), HR-positive/HER2-positive, (n = 148), HR-negative/HER2-positive, (n = 101), and triple-negative (HR-negative/HER2 negative; n = 155). In all, 194 of 249 patients (78%) with HER2-positive tumors received trastuzumab. Univariate and multivariate analyses of factors associated with radiographic complete response (rCR) and pCR were performed.
For the total group, the rCR and pCR rates were 182 of 746 patients (24%) and 179 of 746 patients (24%), respectively, and the highest pCR rate was observed for the triple-negative subtype (57 of 155 patients; 37%) and the HER2-positive subtype (38 of 101 patients; 38%). The overall accuracy of MRI for predicting pCR was 74%. The variables sensitivity, negative predictive value, positive predictive value, and accuracy differed significantly among tumor subtypes, and the greatest negative predictive value was observed in the triple-negative (60%) and HER2-positive (62%) subtypes.
The overall accuracy of MRI for predicting pCR in invasive breast cancer patients who were receiving NCT was 74%. The performance of MRI differed between subtypes, possibly influenced by differences in pCR rates between groups. Future studies will determine whether MRI in combination with directed core biopsy improves the predictive value of MRI for pathologic response.
Available from: PubMed Central
- "The activation of oncogenes and the inactivation of tumor suppressor genes in the regulation of the cellular physiological processes leads not only to abnormal cell proliferation and differentiation, but also to defective apoptosis and drug resistance (8,9). Therefore, it is of great importance for the prevention and treatment of breast cancer to identify novel targets for breast cancer gene therapy (5,10). Previous studies have shown that COX-2 is abnormally expressed in various tumors, and is directly or indirectly involved in carcinogenesis and the development of tumors. "
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ABSTRACT: The aim of the present study was to investigate the effect of cyclooxygenase-2 (COX-2) silencing on the malignant biological behavior of MCF-7 breast cancer cells. COX-2 short hairpin RNA (shRNA) and unassociated sequences were synthesized and a shRNA lentiviral vector was constructed. The vector was transfected into MCF-7 breast cancer cells, in which clones with stable expression were screened out. The expression of COX-2 mRNA and protein was silenced using RNA interference (RNAi). Quantitative polymerase chain reaction, western blotting, a mononuclear cell direct cytotoxicity assay (MTT assay), a cell invasion assay and scratch tests were performed to investigate the downregulation of COX-2 mRNA and protein expression, the proliferative activity and growth rate of MCF-7 breast cancer cells, the glioblastoma multiforme (GBM) penetrating capacity, the cell movement and migratory capacity, and vascular endothelial growth factor (VEGF)-A and VEGF-C protein expression. The results revealed that the sequence-specific shRNA significantly downregulated the expression of COX-2 at the mRNA and protein levels. Furthermore, the downregulation of COX-2 expression markedly decreased the invasive and metastatic capacities of the cells, suppressed the proliferation, decreased the rate of growth, decreased the capacity of GBM penetration and migration, and decreased the protein expression of VEGF-A and VEGF-C, the two key factors that regulate tumor angiogenesis and lymphangiogenesis. In conclusion, the RNAi technique effectively silenced COX-2 gene expression and inhibited MCF-7 breast cancer cell proliferation, invasion and metastasis by decreasing VEGF-A and VEGF-C expression, which regulates tumor angiogenesis and lymphangiogenesis. Therefore, an RNAi technique that targets COX-2 presents a promising prospect for breast cancer gene therapy.
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ABSTRACT: Magnetic resonance imaging (MRI) has been widely applied in the contemporary management of patients with breast cancer and as a screening tool for those at increased risk; however, prospective evidence that the use of breast MRI improves patient outcomes remains limited to screening of known BRCA mutation carriers or women at increased risk based on a strong family history. Despite this, the role of MRI in the routine evaluation of the newly diagnosed breast cancer patient remains a subject of much debate, with widely divergent views on the value of MRI in selecting local therapy. The application of MRI in patients undergoing neoadjuvant therapy is an area of active investigation, with several potential benefits, including predicting response to therapy. We review the current state of the literature on the topics of MRI for screening, MRI and short-term surgical outcomes, MRI and long-term surgical outcomes, and MRI and neoadjuvant chemotherapy as presented at the 2013 Society of Surgical Oncology Susan G. Komen for the Cure Symposium, 9 March 2013.
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