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Context.—: The Oncotype DX Recurrence Score (RS) predicts recurrence and chemotherapy benefit in early-stage estrogen receptor-positive breast cancer patients. Cost and unavailability are 2 major disadvantages of the assay. Multiple models have been developed to predict the RS., Objective.—: To predict RS based on histopathologic and biomarker features, and to measure concordance and correlation with RS of the following 3 algorithms: breast cancer prognostic score, Magee0, and Magee2., Design.—: Breast cancer cases with available RSs were reviewed (n = 442). RS categories were stratified by pathologic and biomarker variables. Histopathologic and biomarker data were abstracted from pathology reports, and RS was calculated by each model. Correlation and concordance between models and RS were calculated., Results.—: Less than 5% of breast cancers with lobular features, low-grade tumors, carcinomas with high progesterone receptor content, or luminal A tumors had an RS greater than 25. Breast cancer prognostic score, Magee0, and Magee2 demonstrated correlation coefficients with RS of 0.63, 0.61, and 0.62, respectively. Two-step discordances were uncommon. When an RS of 25 was used to separate high-risk from non-high-risk cases, concordance rates of 86% to 88% were achieved., Conclusions.—: High RS was observed only in a small percentage of pure or mixed lobular carcinomas, low-grade or luminal A tumors, and tumors with high progesterone receptor expression, suggesting that these cancers may not require Oncotype testing. All 3 surrogate models demonstrated comparable correlation and high concordance with the RS when a cutoff of 25 was used, suggesting their utility in cases where the actual RS is unavailable.

Women of African ancestry suffer higher rates of breast cancer mortality compared with all other groups in the United States. Though the precise reasons for these disparities remain unclear, many recent studies have implicated a role for differences in tumor biology. Using an epitope-validated antibody against the endoplasmic reticulum-associated E3 ligase, gp78, we show that elevated levels of gp78 in patient breast cancer cells predict poor survival. Moreover, high levels of gp78 are associated with poor outcomes in both ER+ and ER- tumors, and breast cancers expressing elevated amounts of gp78 protein are enriched in gene expression pathways that influence cell cycle, metabolism, receptor-mediated signaling, and cell stress response pathways. In multivariate analysis adjusted for subtype and grade, gp78 protein is an independent predictor of poor outcomes in women of African ancestry. Furthermore, gene expression signatures, derived from patients stratified by gp78 protein expression, are strong predictors of recurrence and pathological complete response in retrospective clinical trial data and share many common features with gene sets previously identified to be overrepresented in breast cancers based on race. These findings implicate a prominent role for gp78 in tumor progression and offer insights into our understanding of racial differences in breast cancer outcomes.

The use of digital pathology for the histomorphologic profiling of pathological specimens is expanding the precision and specificity of quantitative tissue analysis at an unprecedented scale; thus, enabling the discovery of new and functionally relevant histological features of both predictive and prognostic significance. In this study, we apply quantitative automated image processing and computational methods to profile the subcellular distribution of the multi-functional transcriptional regulator, Kaiso (ZBTB33), in the tumors of a large racially diverse breast cancer cohort from a designated health disparities region in the United States. Multiplex multivariate analysis of the association of Kaiso's subcellular distribution with other breast cancer biomarkers reveals novel functional and predictive linkages between Kaiso and the autophagy-related proteins, LC3A/B, that are associated with features of the tumor immune microenvironment, survival, and race. These findings identify effective modalities of Kaiso biomarker assessment and uncover unanticipated insights into Kaiso's role in breast cancer progression.

This manuscript presents a protocol to handle, characterize, and image freshly excised human breast tumors using pulsed terahertz imaging and spectroscopy techniques. The protocol involves terahertz transmission mode at normal incidence and terahertz reflection mode at an oblique angle of 30°. The collected experimental data represent time domain pulses of the electric field. The terahertz electric field signal transmitted through a fixed point on the excised tissue is processed, through an analytical model, to extract the refractive index and absorption coefficient of the tissue. Utilizing a stepper motor scanner, the terahertz emitted pulse is reflected from each pixel on the tumor providing a planar image of different tissue regions. The image can be presented in time or frequency domain. Furthermore, the extracted data of the refractive index and absorption coefficient at each pixel are utilized to provide a tomographic terahertz image of the tumor. The protocol demonstrates clear differentiation between cancerous and healthy tissues. On the other hand, not adhering to the protocol can result in noisy or inaccurate images due to the presence of air bubbles and fluid remains on the tumor surface. The protocol provides a method for surgical margins assessment of breast tumors.

The C-terminal binding protein (CtBP) is an NADH-dependent dimeric family of nuclear proteins that scaffold interactions between transcriptional regulators and chromatin-modifying complexes. Its association with poor survival in several cancers implicates CtBP as a promising target for pharmacological intervention. We employed computer-assisted drug design to search for CtBP inhibitors, using quantitative structure-activity relationship (QSAR) modeling and docking. Functional screening of these drugs identified 4 compounds with low toxicity and high water solubility. Micro molar concentrations of these CtBP inhibitors produces significant de-repression of epigenetically silenced pro-epithelial genes, preferentially in the triple-negative breast cancer cell line MDA-MB-231. This epigenetic reprogramming occurs through eviction of CtBP from gene promoters; disrupted recruitment of chromatin-modifying protein complexes containing LSD1, and HDAC1; and re-wiring of activating histone marks at targeted genes. In functional assays, CtBP inhibition disrupts CtBP dimerization, decreases cell migration, abolishes cellular invasion, and improves DNA repair. Combinatorial use of CtBP inhibitors with the LSD1 inhibitor pargyline has synergistic influence. Finally, integrated correlation of gene expression in breast cancer patients with nuclear levels of CtBP1 and LSD1, reveals new potential therapeutic vulnerabilities. These findings implicate a broad role for this class of compounds in strategies for epigenetically targeted therapeutic intervention.

Cancer has become the leading cause of death in North Carolina (NC) (North Carolina DHHS, State Center for Health Statistics 2015) and the eastern region of North Carolina (ENC) has experienced greater cancer mortality than the remainder of the state. The Pitt County Breast Wellness Initiative-Education (PCBWI-E) provides culturally tailored breast cancer education and navigation to screening services for uninsured/underinsured women in Pitt and Edgecombe Counties in ENC. PCBWI-E created a network of 23 lay breast health educators, and has educated 735 women on breast health and breast cancer screening guidelines. Navigation services have been provided to 365 women, of which 299 were given breast health assessments, 193 were recommended for a mammogram, and 138 were screened. We have identified five lessons learned to share in the successful implementation of a community-based breast cancer screening intervention: (1) community partnerships are critical for successful community-based cancer screening interventions; (2) assuring access to free or low-cost screening and appropriate follow-up should precede interventions to promote increased use of breast cancer screening; (3) the reduction of system-based barriers is effective in increasing cancer screening; (4) culturally tailored interventions can overcome barriers to screening for diverse racial/ethnic and socioeconomic groups; and (5) multi-component interventions that include multiple community health strategies are effective in increasing screening.