Dishevelled 2 regulates cancer cell proliferation and T cell mediated immunity in HER2-positive breast cancer.

BACKGROUND: Dishevelled paralogs (DVL1, 2, 3) are key mediators of Wnt pathway playing a role in constitutive oncogenic signaling influencing the tumor microenvironment. While previous studies showed correlation of ß-catenin with T cell gene expression, little is known about the role of DVL2 in modulating tumor immunity. This study aimed to uncover the novel interaction between DVL2 and HER2-positive (HER2+) breast cancer (BC) in regulating tumor immunity and disease progression. METHODS: DVL2 loss of function studies were performed with or without a clinically approved HER2 inhibitor, Neratinib in two different HER2+ BC cell lines. We analyzed RNA (RT-qPCR) and protein (western blot) expression of classic Wnt markers and performed cell proliferation and cell cycle analyses by live cell imaging and flow cytometry, respectively. A pilot study in 24 HER2+ BC patients was performed to dissect the role of DVL2 in tumor immunity. Retrospective chart review on patient records and banked tissue histology were performed. Data were analyzed in SPSS (version 25) and GraphPad Prism (version 7) at a significance p < 0.05. RESULTS: DVL2 regulates the transcription of immune modulatory genes involved in antigen presentation and T cell maintenance. DVL2 loss of function down regulated mRNA expression of Wnt target genes involved in cell proliferation, migration, invasion in HER2+ BC cell lines (±Neratinib). Similarly, live cell proliferation and cell cycle analyses reveal that DVL2 knockdown (±Neratinib) resulted in reduced proliferation, higher growth arrest (G1), limited mitosis (G2/M) compared to non-targeted control in one of the two cell lines used. Analyses on patient tissues who received neoadjuvant chemotherapy (n = 14) further demonstrate that higher DVL2 expression at baseline biopsy pose a significant negative correlation with % CD8α levels (r = - 0.67, p < 0.05) while have a positive correlation with NLR (r = 0.58, p < 0.05), where high NLR denotes worse cancer prognosis. These results from our pilot study reveal interesting roles of DVL2 proteins in regulating tumor immune microenvironment and clinical predictors of survival in HER2+ BC. CONCLUSION: Our study demonstrates potential immune regulatory role of DVL2 proteins in HER2+ BC. More in-depth mechanistic studies of DVL paralogs and their influence on anti-tumor immunity may provide insight into DVLs as potential therapeutic targets benefiting BC patients.

The Role of Cryoablation in Breast Cancer Beyond the Oncologic Control: COST and Breast-Q Patient-Reported Outcomes.

BACKGROUND: Cryoablation has been established as a minimally invasive alternative to resection of early-stage breast cancer; however, there are no data on the cost and impact on patients' financial, psychosocial, sexual, physical, and cosmetic outcomes utilizing this approach. This study compares cost-effectiveness and patient-reported quality-of-life factors in cryoablation versus resection. METHODS: Women with early-stage, low-risk infiltrating ductal carcinomas ≤ 1.5 cm underwent cryoablation or resection. Adjuvant therapy was provided according to tumor board recommendations. Direct and indirect costs were tracked for both groups. Financial toxicity and well-being outcome were measured by administering the Comprehensive Score of Financial Toxicity (COST) and BREAST-Q surveys, respectively, at 6-month follow-up. RESULTS: Of the 34 eligible patients, 14 (41.1%) consented for cryoablation and 20 (58.8%) underwent resection. The median (centile) (range) follow-up was 35.0 (21.3) (15-50) months for cryoablation vs. 25 (20.8) (17-50) months for resection [p = 0.6479]. Mean (standard deviation) cost of care for cryoablation versus resection was $2221.70 (615.70) versus $16,896.50 (1332.40) [p < 0.0001], and median financial well-being scores for the cryoablation versus resection groups were 38.0 (34.5, 40.0) versus 10 (5.3, 14.0) [p < 0.0001]. Poor financial well-being was directly correlated with the cost of care [p < 0.0001]. Median psychosocial well-being scores were similar across both groups, however the cryoablation group had higher scores for physical [100 (100, 100) vs. 89 (79, 100); p = 0.0141], sexual [100 (91, 100) vs. 91 (87.5, 91); p = 0.0079], and cosmetic [100 (100, 100) vs. 88 (88, 100); p = 0.0171] outcomes. CONCLUSION: Cryoablation offers a cost-effective and quality-of-life advantage compared with resection for early-stage, low-risk breast cancer.

Cost savings analysis of prescription assistance programs at a student-run free clinic.

The Free Clinic at Lubbock Impact (TFC) is a student-run, volunteer free clinic affiliated with Texas Tech University Health Sciences Center in Lubbock, Texas, that provides free weekly health services to the local uninsured patient population. The clinic also helps patients enroll in prescription assistance programs (PAPs) from pharmaceutical companies, which supply eligible patients with certain medications at little or no cost. This study presents a cost savings analysis of TFC patients enrolled in PAPs from February 2019 through February 2020. Cost savings were calculated by matching medication doses and units with the cost per unit for each brand-name medication listed on GoodRx.com at Walgreens pharmacies located in TFC's zip code, 79410. Sixty-one patients received 23 different medications with a total cost savings value of $222,563. Medications were sorted into diabetic, respiratory, and miscellaneous disease categories, for which cost savings totaled $114,110, $60,219, and $48,234, respectively. This study highlights the value of utilizing PAPs at a free clinic to address the barrier of medication cost for uninsured patients in Lubbock, Texas, and surrounding areas.