Integrating Biology and Access to Care in Addressing Breast Cancer Disparities: 25 Years’ Research Experience in the Carolina Breast Cancer Study

Purpose of Review: To review research on breast cancer mortality disparities, emphasizing research conducted in the Carolina Breast Cancer Study, with a focus on challenges and opportunities for integration of tumor biology and access characteristics across the cancer care continuum. Recent Findings: Black women experience higher mortality following breast cancer diagnosis, despite lower incidence compared to white women. Biological factors, such as stage at diagnosis and breast cancer subtypes, play a role in these disparities. Simultaneously, social, behavioral, environmental, and access to care factors are important. However, integrated studies of biology and access are challenging and it is uncommon to have both data types available in the same study population. The central emphasis of phase 3 of the Carolina Breast Cancer Study, initiated in 2008, was to collect rich data on biology (including germline and tumor genomics and pathology) and health care access in a diverse study population, with the long-term goal of defining intervention opportunities to reduce disparities across the cancer care continuum. Summary: Early and ongoing research from CBCS has identified important interactions between biology and access, leading to opportunities to build greater equity. However, sample size, population-specific relationships among variables, and complexities of treatment paths along the care continuum pose important research challenges. Interdisciplinary teams, including experts in novel data integration and causal inference, are needed to address gaps in our understanding of breast cancer disparities

Developmental expression and differential regulation by retinoic acid ofXenopus COUP-TF-A andCOUP-TF-B

COUP-TFs (Chicken Ovalbumin Upstream Promoter Transcription Factors) have been proposed to be negative regulators of retinoid receptor-mediated transcriptional activation. In a previous paper we reported the cloning of aXenopus (x) COUP-TF (Matharu, P.J. and Sweeney, G.E. (1992) Biochim. Biophys. Acta 1129, 331–334). Here we describe the cloning of a secondxCOUP-TF. Amino acid sequence comparison between these twoXenopus COUP-TFs revealed a high level of similarity. Extensive amino acid sequence conservation was found among allDrosophila, Xenopus, zebrafish and mammalianCOUP-TF genes examined. Phylogenetic tree analyses indicate that the vertebrate COUP-TFs fall into three classes. The twoXenopus COUP-TF genes show similar temporal expression patterns: both are expressed from the end of gastrulation. In situ hybridization studies reveal complex expression patterns in the developing central nervous system (CNS), besides expression in the eye and in some mesodermal tissues. Retinoic acid (RA) treatment enhancesxCOUP-TF-A expression in neurula stage embryos, whereas the expression ofxCOUP-TF-B is inhibited during the same developmental period. The strictly conserved amino acid sequences and the strong similarities between the expression patterns of the two differentxCOUP-TFs on the one hand, and other vertebrateCOUP-TF homologues on the other, make it likely that COUP-TFs have a conserved role in patterning the nervous system

Derivation of inhalation toxicity reference values for propylene oxide using mode of action analysis: Example of a threshold carcinogen.

Propylene oxide (PO) is an important industrial chemical used primarily in the synthesis of other compounds. Inhalation carcinogenesis studies in rodents, with no-observed-adverse-effect levels (NOAELs) of 100 and 200 ppm, have revealed that chronic, high exposure to PO can induce tumors at the site of contact. Despite these characteristics, there is no evidence that typical environmental or occupational exposures to PO constitute a health risk for humans. The nongenotoxic effects of PO (glutathione depletion and cell proliferation) that augment its DNA-reactive and non-DNA-reactive genotoxicity are expected to be similar in humans and rodents. Available evidence on mode-of-action suggests that cancer induction by PO at the site of contact in rodents is characterized by a practical threshold. Human toxicity reference values for potential carcinogenic effects of PO were derived based on nasal tumors identified in rodent studies and specified uncertainty factors. The 95% lower confidence limit on the dose producing a 10% increase in additional tumor risk (LED10) was calculated using the rat and mouse data sets. The human reference values derived from the rat and mouse LED10 values were 0.7 and 0.5 ppm PO, respectively. A similar noncancer reference value, 0.4 ppm, was derived on the basis of non-neoplastic nasal effects in rats