Screening for Breast Cancer Risk: An Analysis of Under-recognized Risk Factors and Comparison of Interventions.

Recognition of patients at high risk (HR) for breast cancer allows earlier screening and opportunities for risk reduction. We compare patients referred to our breast clinic as HR vs referrals for other reason (ROR) and found to be HR. We evaluate under-recognized factors and treatment differences. A retrospective chart review of patients found to be HR but referred for any reason to our breast clinic from July 2012 to December 2022 was performed. Referral reason, demographics, hormonal history, family history, and other risk factors were evaluated and compared (HR vs ROR). While other risk models were used for screening, Gail and Tyrer-Cuzick version 7 (TCv7) were used for comparison. Breast imaging received, hormonal therapy, and genetics referral evaluations were compared. 195 patients were referred to our breast team, 113 (58%) were referred as HR while 82 (42%) were ROR. Average age was 47 years old. 175 (91%) were Caucasian. 74 (65.5%) were referred for genetic testing, and 32 (26%) tested positive for a genetic mutation (n = 10, 12% ROR). 67 (35%) were recommended chemoprevention (n = 32, 16.4% took chemoprevention). 6 (3.1%) underwent prophylactic mastectomies and 163 (85%) had supplemental breast imaging. Comparison of HR vs ROR did not show significant differences in hormonal factors or treatments received; however, TCv7 was higher in the group referred as HR (P < .001). Our study showed that HR patients are more commonly referred secondary to family history but undergo similar treatments as those ROR. Accessibility to screening tools and education of risk factors, especially in minorities and those not otherwise being screened, may help better recognize HR.

Synthetic Control of Signal Flow Within a Bacterial Multi-Kinase Network.

The signal processing capabilities of bacterial signaling networks offer immense potential for advanced phospho-signaling systems for synthetic biology. Emerging models suggest that complex development may require interconnections between what were once thought to be isolated signaling arrays. For example, Caulobacter crescentus achieves the feat of asymmetric division by utilizing a novel pseudokinase DivL, which senses the output of one signaling pathway to modulate a second pathway. It has been proposed that DivL reverses signal flow by exploiting conserved kinase conformational changes and protein-protein interactions. We engineered a series of DivL-based modulators to synthetically stimulate reverse signaling of the network in vivo. Stimulation of conformational changes through the DivL signal transmission helix resulted in changes to hallmark features of the network: C. crescentus motility and DivL accumulation at the cell poles. Additionally, mutations to a conserved PAS sensor transmission motif disrupted reverse signaling flow in vivo. We propose that synthetic stimulation and sensor disruption provide strategies to define signaling circuit organization principles for the rational design and validation of synthetic pathways.