A dynamic web-based decision aid to improve informed choice in organised breast cancer screening. A pragmatic randomised trial in Italy.
- 作者列表："Roberto A","Colombo C","Candiani G","Satolli R","Giordano L","Jaramillo L","Castagno R","Mantellini P","Falini P","Carnesciali E","Valenza M","Costa L","Campari C","Caroli S","Faggiano RC","Orione L","Belmessieri B","Marchiò V","Deandrea S","Silvestri A","Luciano D","Paci E","Mosconi P
BACKGROUND:Improving the quality of information and communication is a priority in organised breast cancer screening and an ethical duty. Programmes must offer the information each woman is looking for, promoting informed decision-making. This study aimed to develop and evaluate a web-based dynamic decision aid (DA). METHODS:A pragmatic randomised trial carried out in six regional organised screening programmes recruited women at the first invitation receiving DA or a web-based standard brochure (SB). The primary outcome was informed choice measured on knowledge, attitudes, and intentions. Follow-up period: 7-10 days. Secondary outcomes included participation rate, satisfaction, decisional conflict, and acceptability of DA. RESULTS:Two thousand one hundred and nineteen women were randomised and 1001 completed the study. Respectively, 43.9% and 36.9% in the DA and SB reached the informed choice. The DA gave a 13-point higher proportion of women aware about overdiagnosis compared to SB (38.3% versus 25.2%, p < 0.0001). The percentage of women attending screening was the same: 84% versus 83%. Decisional conflict was significantly lower in the DA group (14.4%) than in the SB group (19.3%). CONCLUSION:DA increases informed choice. Complete information including the pros, cons, controversies, and overdiagnosis-overtreatment issues boost a woman's knowledge without reducing the rate of actual screening participation. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov number NCT03097653.
背景: 提高信息和沟通的质量是有组织乳腺癌筛查的优先事项，也是一项伦理义务。方案必须提供每位妇女都在寻找的信息，促进知情决策。本研究旨在开发和评估一种基于网络的动态决策辅助工具 (DA)。 方法: 在 6 个区域有组织的筛查项目中进行的一项实用随机试验，在接受 DA 或基于网络的标准手册 (SB) 的第一次邀请时招募了女性。主要结局是根据知识、态度和意图测量的知情选择。随访期: 7-10 天。次要结局包括参与率、满意度、决策冲突和 DA 的可接受性。 结果: 119 名妇女被随机分组，1001 人完成了研究。分别有 43.9% 和 36.9% 的 DA 和 SB 达到了知情选择。与 SB 相比，DA 给出的女性意识到过度诊断的比例较高 13 分 (38.3% 对 25.2%，p <0.0001)。参加筛查的女性比例相同: 84% 对 83%。决策冲突在 DA 组 (14.4%) 显著低于 SB 组 (19.3%)。 结论: DA 增加知情选择。包括利弊、争议和过度诊断-过度治疗问题在内的完整信息可在不降低实际筛查参与率的情况下提高女性的知识水平。 临床试验注册: ClinicalTrials.gov 编号 nct03097653。
METHODS::The emerging significance of the bitter taste receptors (T2Rs) role in the extraoral tissues alludes to their potential role in many pathophysiological conditions. The dysregulation of T2R expression and function in disease conditions has now been demonstrated in airways diseases, neurological disorders, and in some cancers. However, the role of T2Rs in the pathophysiology of breast cancer is unexplored thus far. Previously, we demonstrated differential expression of the 25 T2Rs in breast cancer (BC) cells. Based on our previous findings we selected two T2Rs, T2R4 and T2R14 for this work. The objective of the current study is to investigate the expression of T2R4 and T2R14 in BC clinical samples and to examine their physiological role using highly metastatic BC and non-cancerous cell lines. Using approaches, which involve receptor knockdown, pharmacological activation and biochemical assays we report that (i) T2R4 and T2R14 expression patterns are dissimilar, with decreased levels of T2R4 and increased levels of T2R14 in BC clinical samples compared to non-cancerous controls. (ii) Activation of T2Rs with their respective agonist elicited physiological responses in metastatic breast cancer cells, and no responses were seen in non-tumorigenic breast epithelial cells. (iii) Agonist activation of T2Rs (irrespective of T2R subtype) induced anti-proliferative, pro-apoptotic, and anti-migratory responses in highly metastatic breast cancer cells. Taken together, our findings demonstrate that the chemosensory T2R signaling network is involved in evoking physiological responses in the metastatic breast cancer cell line.
METHODS::RAD50 is commonly depleted in basal-like breast cancer with concomitant absence of INPP4B and several tumor suppressors such as BRCA1 and TP53. Our previous study revealed that INPP4B and RAD50 interact and such an interaction is associated with breast cancer survival at the transcriptional, translational and genomic levels. In the present study, we explored single nucleotide polymorphisms (SNPs) of these two genes that have synergistic effects on breast cancer survival to decipher mechanisms driving their interactions at the genetic level. The Cox's proportional hazards model was used to test whether SNPs of these two genes are interactively associated with breast cancer survival, following expression quantitative trait loci (eQTL) analysis and functional investigations. Our study revealed two disease-associating blocks, each encompassing five and two non-linkage disequilibrium linked SNPs of INPP4B and RAD50, respectively. Concomitant presence of any rare homozygote from each disease-associating block is synergistically prognostic of poor breast cancer survival. Such synergy is mediated via bypassing pathways controlling cell proliferation and DNA damage repair, which are represented by INPP4B and RAD50. Our study provided genetic evidence of interactions between INPP4B and RAD50, and deepened our understandings on the orchestrated genetic machinery governing tumor progression.
METHODS:BACKGROUND:Increased usage of genomic risk assessment assays suggests increased reliance on data provided by these assays to guide therapy decisions. The current study aimed to assess the change in treatment decision and physician confidence based on the 70-gene risk of recurrence signature (70-GS, MammaPrint) and the 80-gene molecular subtype signature (80-GS, BluePrint) in early stage breast cancer patients. METHODS:IMPACt, a prospective, case-only study, enrolled 452 patients between November 2015 and August 2017. The primary objective population included 358 patients with stage I-II, hormone receptor-positive, HER2-negative breast cancer. The recommended treatment plan and physician confidence were captured before and after receiving results for 70-GS and 80-GS. Treatment was started after obtaining results. The distribution of 70-GS High Risk (HR) and Low Risk (LR) patients was evaluated, in addition to the distribution of 80-GS compared to IHC status. RESULTS:The 70-GS classified 62.5% (n = 224/358) of patients as LR and 37.5% (n = 134/358) as HR. Treatment decisions were changed for 24.0% (n = 86/358) of patients after receiving 70-GS and 80-GS results. Of the LR patients initially prescribed CT, 71.0% (44/62) had CT removed from their treatment recommendation. Of the HR patients not initially prescribed CT, 65.1% (41/63) had CT added. After receiving 70-GS results, CT was included in 83.6% (n = 112/134) of 70-GS HR patient treatment plans, and 91.5% (n = 205/224) of 70-GS LR patient treatment plans did not include CT. For patients who disagreed with the treatment recommended by their physicians, most (94.1%, n = 16/17) elected not to receive CT when it was recommended. For patients whose physician-recommended treatment plan was discordant with 70-GS results, discordance was significantly associated with age and lymph node status. CONCLUSIONS:The IMPACt trial showed that treatment plans were 88.5% (n = 317/358) in agreement with 70-GS results, indicating that physicians make treatment decisions in clinical practice based on the 70-GS result. In clinically high risk, 70-GS Low Risk patients, there was a 60.0% reduction in treatment recommendations that include CT. Additionally, physicians reported having greater confidence in treatment decisions for their patients in 72% (n = 258/358) of cases after receiving 70-GS results. TRIAL REGISTRATION:"Measuring the Impact of MammaPrint on Adjuvant and Neoadjuvant Treatment in Breast Cancer Patients: A Prospective Registry" (NCT02670577) retrospectively registered on Jan 27, 2016.