Ductal carcinoma in situ (DCIS) of the breast is a group of heterogeneous epithelial proliferations confined to the milk ducts that nearly always present in asymptomatic women on breast cancer screening. A stage 0, preinvasive breast cancer, increased detection of DCIS was initially hailed as a means to prevent invasive breast cancer through surgical treatment with adjuvant radiation and/or endocrine therapies. However, controversy in the medical community has emerged in the past two decades that a fraction of DCIS represents overdiagnosis, leading to unnecessary treatments and resulting morbidity. The imaging hallmarks of DCIS include linearly or segmentally distributed calcifications on mammography or nonmass enhancement on breast MRI. Imaging features have been shown to reflect the biological heterogeneity of DCIS lesions, with recent studies indicating MRI may identify a greater fraction of higher-grade lesions than mammography does. There is strong interest in the surgical, imaging, and oncology communities to better align DCIS management with biology, which has resulted in trials of active surveillance and therapy that is less aggressive. However, risk stratification of DCIS remains imperfect, which has limited the development of precision therapy approaches matched to DCIS aggressiveness. Accordingly, there are opportunities for breast imaging radiologists to assist the oncology community by leveraging advanced imaging techniques to identify appropriate patients for the less aggressive DCIS treatments.
Early detection of breast cancer is crucial for better prognosis and successful treatment of the patients. Development of novel methods for screening for breast cancer is needed for early detection and diagnosis. The human immune system responds to tumor-specific antigens in the pre-malignant stage of breast cancer and produces specific antibodies, which can be detected as potential breast cancer biomarkers. Due to the limited availability of well-annotated pre-cancer and post-cancer sera from human subjects, we performed serial serum collection in a neu transgenic mouse model from the age of 10 weeks to the terminal stage of disease. Using a technique called serological screening of cDNA expression library (SEREX), a high-throughput method to rapidly screen recombinant proteins expressed in a bacteriophage-based cDNA library, we have previously identified tumor antigens in the late stage of neu breast cancers. The mouse tumors have similar immunogenicity as their human counterparts due to the fact that some of these antigens are also immunogenic in human. Indeed, we have found that one mouse antigen called gelsolin, shares 93% homology with human gelsolin and has the highest response to human serum antibody among other antigens. In an ELISA analysis using the serum samples from 50 breast cancer cases and 50 normal donors, the area-under-curve (AUC) value of the receiver-operating-characteristic (ROC) curve of gelsolin ELISA detects more than 70% of cancer patients. Using the SEREX technique, we sought to further identify the early-stage serum antibody biomarkers by comparing the pre-cancer, early stage, and late stage sera from the same mouse. We have identified three early-stage biomarkers, A20/TNFaip3, Rpl5, and Pdhx, in neu mice. In summary, we conclude that identification of tumor antigens in the neu transgenic animal model is useful for the discovery of serum antibody biomarkers for early detection and diagnosis.
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 2742.
Breast MRI is the most sensitive imaging modality for the assessment of newly diagnosed breast cancer extent and can detect additional mammographically and clinically occult breast cancers in the ipsilateral and contralateral breasts. Nonetheless, appropriate use of breast MRI in the setting of newly diagnosed breast cancer remains debated. Though highly sensitive, MRI is less specific and may result in false positives and overestimation of disease when MRI findings are not biopsied prior to surgical excision. Furthermore, improved anatomic depiction of breast cancer on MRI has not consistently translated to improved clinical outcomes, such as lower rates of re-excision or breast cancer recurrence, though there is a paucity of well-designed studies examining these issues. In addition, current treatment paradigms have been developed in the absence of this more accurate depiction of disease span, which likely has limited the value of MRI. These issues have led to inconsistent and variable utilization of preoperative MRI across practice settings and providers. In this review, we discuss the history of breast MRI and its current use and recommendations with a focus on the preoperative setting. We review the evidence surrounding the use of preoperative MRI in the evaluation of breast malignancies and discuss the data on breast MRI in the setting of specific patient factors often used to determine breast MRI eligibility, such as age, index tumor phenotype, and breast density. Finally, we review the impact of breast MRI on surgical outcomes (re-excision and mastectomy rates) and long-term breast recurrence and survival outcomes.
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