Racial disparities in treatment-related cardiovascular toxicities amongst women with breast cancer: a scoping review.

PURPOSE: Black women often experience poorer breast cancer-related outcomes and higher mortality than white women. A contributor to this disparity may relate to the disproportionate burden of cancer treatment-related cardiovascular (CV) toxicities. The objective of this review is to identify studies that report racial differences in CV toxicity risk. METHODS: Medline and Embase were searched for studies that assessed CV toxicities as the outcome(s) and included Black and White women with breast cancer. Studies were selected based on inclusion/exclusion criteria and through the use of multiple reviewers. RESULTS: The review included 13 studies following a review of 409 citations and 49 full-text articles. All studies were retrospective and 8/13 utilized data from the Surveillance, Epidemiology, and End Results-Medicare linked database. Trastuzumab was the most frequently studied treatment. The proportion of Black women in these studies ranged from 5.5 to 63%. A majority of studies reported a higher risk of CV toxicity amongst Black women when compared to white women (93%). Black women had up to a two times higher risk of CV toxicity (HR, 2.73 (CI, 1.24 to 6.01)) compared to white women. Only one study evaluated the role of socioeconomic factors in explaining racial differences in CV toxicity; however, the disparity remained even after adjusting for these factors. CONCLUSIONS: There is a critical need for more longitudinal studies that evaluate multilevel factors (e.g., psychosocial, biological) that may help to explain this disparity. IMPLICATIONS FOR CANCER SURVIVORS: Black cancer survivors may require additional surveillance and mitigation strategies to decrease disproportionate burden of CV toxicities.

E-liquids and vanillin flavoring disrupts retinoic acid signaling and causes craniofacial defects in Xenopus embryos.

Environmental teratogens such as smoking are known risk factors for developmental disorders such as cleft palate. While smoking rates have declined, a new type of smoking, called vaping is on the rise. Vaping is the use of e-cigarettes to vaporize and inhale an e-liquid containing nicotine and food-like flavors. There is the potential that, like smoking, vaping could also pose a danger to the developing human. Rather than waiting for epidemiological and mammalian studies, we have turned to an aquatic developmental model, Xenopus laevis, to more quickly assess whether e-liquids contain teratogens that could lead to craniofacial malformations. Xenopus, like zebrafish, has the benefit of being a well-established developmental model and has also been effective in predicting whether a chemical could be a teratogen. We have determined that embryonic exposure to dessert flavored e-liquids can cause craniofacial abnormalities, including an orofacial cleft in Xenopus. To better understand the underlying mechanisms contributing to these defects, transcriptomic analysis of the facial tissues of embryos exposed to a representative dessert flavored e-liquid vapor extract was performed. Analysis of differentially expressed genes in these embryos revealed several genes associated with retinoic acid metabolism or the signaling pathway. Consistently, retinoic acid receptor inhibition phenocopied the craniofacial defects as those embryos exposed to the vapor extract of the e-liquid. Such malformations also correlated with a group of common differentially expressed genes, two of which are associated with midface birth defects in humans. Further, e-liquid exposure sensitized embryos to forming craniofacial malformations when they already had depressed retinoic acid signaling. Moreover, 13-cis-retinoic acid treatment could significantly reduce the e-liquid induced malformation in the midface. Such results suggest the possibility of an interaction between retinoic acid signaling and e-liquid exposure. One of the most popular and concentrated flavoring chemicals in dessert flavored e-liquids is vanillin. Xenopus embryos exposed to this chemical closely resembled embryos exposed to dessert-like e-liquids and a retinoic acid receptor antagonist. In summary, we determined that e-liquid chemicals, in particular vanillin, can cause craniofacial defects potentially by dysregulating retinoic acid signaling. This work warrants the evaluation of vanillin and other such flavoring additives in e-liquids on mammalian development.