Award Application Deadline:
Late-Breaking Abstract Submission Deadline:
- 9:15 AM
Breast Ductal Carcinoma In Situ - Precursor to Invasive Breast Cancer
William B. Coleman PhD
University of North Carolina Chapel Hill School of Medicine - Department of Pathology & Laboratory Medicine
Abstract: Breast Ductal Carcinoma In Situ - Precursor to Invasive Breast Cancer The natural history of breast cancer unfolds with the development of ductal carcinoma in situ (DCIS) in the otherwise apparently normal breast tissue, and then evolution of this pre-invasive lesion into invasive ductal carcinoma. Ductal carcinoma in situ (DCIS) represents a commonly diagnosed breast lesion that accounts for 25% of breast neoplasms diagnosed in the United States with ~55,000 new cases each year. DCIS is by definition non-invasive, but can vary from low-grade (and not life threatening) to high-grade lesions that may contain invasive elements. As such, DCIS (especially high-grade lesions) represent a risk factor for development of invasive breast cancer. Consistent with this suggestion, the incidence of DCIS increases with age in parallel with the incidence of invasive breast cancer, and many invasive breast cancers are associated with proximal DCIS lesions. Over the last 20 years, invasive breast cancers have been characterized using gene expression analysis and classified into several molecular subtypes that have implications for treatment and long-term survival. More recently, analyses of gene expression patterns in DCIS has identified similar molecular subtypes. The correspondence between molecular subtypes of DCIS and invasive cancers suggests that the DCIS lesions may be direct precursors of the invasive cancers. Some studies suggest that the diversity of molecular subtypes observed in invasive breast cancer emerge from an evolution of low-grade to high-grade DCIS lesions. Hence, early alterations in the breast epithelium leading to the development of pre-invasive DCIS lesions may determine the severity of invasive breast cancers that subsequently develop in many patients. Currently, >500,000 women are alive that have a prior diagnosis of DCIS, reflecting an enormous pool of patients at increased risk for development of recurrent disease (DCIS or invasive breast cancer). Given the prevalence of DCIS, expansion and improvement of our understanding of the molecular pathogenesis of this disease will be essential to the development of new strategies for effective prevention of breast cancer and improved treatment of patients with pre-invasive breast neoplasms.
- 10:00 AM
Gene Expression Patterns in Breast DCIS Predict Aggressiveness of Disease
Lawrence J. Solin MD
Albert Einstein Medical Center - Department of Radiation Oncology
Ductal carcinoma in situ (DCIS; intraductal carcinoma) is a non-obligate precursor of invasive carcinoma of the breast. Prospective randomized trials have demonstrated that adding radiation treatment and tamoxifen after lumpectomy (surgical excision) significantly improve the risk of recurrence, but not survival. Given the need to develop molecular tools in the setting of selecting local treatment for DCIS, the 12-gene Oncotype DX DCIS Score was developed and validated to predict risks of local recurrence and the subset of invasive local recurrence after lumpectomy alone (without radiation treatment), independent of tamoxifen use. The DCIS Score includes 12 genes, which are a subset of the 21 genes in the Onctotype DX Recurrence Score (for invasive carcinoma). These 12 genes are comprised of five genes in the proliferation group, progesterone receptor, GSTM1, and five reference genes. Using the ECOG-ACRIN E5194 study in which patients were treated with lumpectomy (without radiation treatment), the DCIS Score was associated with the 10-year risks of developing an ipsilateral breast event (IBE; local recurrence) (p = 0.006) and the subset of an invasive IBE (p = 0.003). On multivariable analysis, the DCIS Score, tumor size, and menopausal status were independently statistically significant for local recurrence (all p d 0.02). Analysis of grade did not demonstrate a significant correlation with local recurrence. These results validated the DCIS Score as a predictor of local recurrence and invasive local recurrence, quantified the 10-year risk of local recurrence, and provided independent information beyond conventional clinical and pathologic variables. The 12-gene DCIS Score was independently validated a second time using a population-based cohort from Ontario, Canada. Comparing the data from the ECOG-ACRIN E5914 study and the population-based cohort study from Canada demonstrates remarkably similar results, including local recurrence, the subset of invasive local recurrence, and hazard function. The similar results in these two validation studies support the clinical implementation of the 12-gene DCIS Score in accordance with rigorous scientific principles for tumor biomarker development and validation.
- 10:45 AM
MicroRNA Expression Signatures Predict Aggressiveness of Breast DCIS
Bethany N. Hannafon PhD
University of Oklahoma Health Science Center - Department of Pathology
Abstract: Ductal carcinoma in situ (DCIS) is defined as a proliferation of neoplastic cells within the duct of the mammary gland, that have not invaded into the surrounding stroma. DCIS is considered a precursor to invasive ductal carcinoma (IDC), however, approximately only half of DCIS may progress to IDC, if left untreated. Current research has shown that the genomic and transcriptomic changes observed in IDC are also present in DCIS, indicating that the malignant nature of DCIS is defined prior to progression. However, important questions remain, including the identification of the specific changes required for malignant progression and prognostic indicators of the aggressiveness of DCIS. microRNAs are small (17-21 nucleotides) regulatory RNAs that modulate gene expression by complementary binding to target mRNAs and inducing translational repression and/or mRNA degradation. microRNAs regulate many important normal cellular processes and contribute to the pathogenesis of many diseases, including breast cancer. In the last decade, research has shown that microRNA expression is dysregulated in IDC, and that these changes are already present at the DCIS stage. Therefore, microRNAs may provide the necessary information required to identify a prognostic indicator of DCIS progression. Here, we will review the microRNA signatures identified in DCIS and discuss how they may be utilized to predict the aggressiveness of DCIS.
- 11:30 AM
The Future of Molecular Testing in Breast DCIS
Gregory J. Tsongalis PhD
Dartmouth-Hitchcock Medical Center - Department of Pathology
Abstract: Ductal carcinoma in situ (DCIS) accounts for up to 25% of all breast cancers yet only a small percentage of these cases will progress to invasive ductal carcinoma of the breast. Identifying which DCIS patients will progress and which will not, continues to elude investigators with significant negative impact on patient management. Advanced genomic and proteomic technologies are on the verge of identifying novel biomarkers associated with progression of disease and response to therapy. This session will focus on the potential diagnostic and prognostic implications of these discoveries and how the face of laboratory testing for DCIS may change.