Adherence trajectories of adjuvant endocrine therapy in the five years after its initiation among women with non-metastatic breast cancer: a cohort study using administrative databases.
非转移性乳腺癌女性患者开始辅助内分泌治疗后 5 年的依从性轨迹: 一项使用管理数据库的队列研究。
- 作者列表："Lambert-Côté L","Bouhnik AD","Bendiane MK","Bérenger C","Mondor M","Huiart L","Lauzier S
PURPOSE:Despite the benefits of adjuvant endocrine therapy (AET) for reducing recurrence and mortality risks after hormone-sensitive breast cancer, AET adherence is sub-optimal for a high proportion of women. However, little is known about long-term patterns of AET adherence over the minimally recommended 5 years. Our objectives were to: (1) identify 5-year AET adherence trajectory groups; (2) describe trajectory groups according to adherence measures traditionally used (i.e., Proportion of Days Covered); and (3) explore factors associated with trajectories. METHODS:We conducted a 5-year cohort study using data from a French national study that included AET dispensing data. Women diagnosed with first non-metastatic breast cancer and having at least 1 AET dispensing in the 12 months after diagnosis were included. Group-based trajectory modeling was used to identify adherence trajectory groups by clustering similar patterns of monthly AET dispensing. Multinomial logistic regressions were used to identify factors associated with trajectories. RESULTS:Among 674 women, five AET adherence trajectory groups were identified: (1) quick decline and stop (5.2% of women); (2) moderate decline and stop (6.4%); (3) slow decline (17.2%); (4) high adherence (30.0%); and (5) maintenance of very high adherence (41.2%). Mean 5-year Proportion of Days Covered varied from 10 to 97% according to trajectories. Women who did not receive chemotherapy or a personalized care plan were more likely to belong to trajectories where AET adherence declined and stopped. CONCLUSION:Our results provide information on the diversity of longitudinal AET adherence patterns, the timing of decline and discontinuation and associated factors that could inform healthcare professionals.
目的: 尽管辅助内分泌治疗 (AET) 可降低激素敏感性乳腺癌术后复发和死亡风险，但 AET 依从性对于高比例的女性来说并不理想。然而，对最低推荐 5 年 AET 依从性的长期模式知之甚少。我们的目标是 :( 1) 确定 5 年 AET 依从性轨迹组; (2) 根据传统使用的依从性测量 (即,覆盖天数的比例); (3) 探索与轨迹相关的因素。 方法: 我们使用法国国家研究的数据进行了一项为期 5 年的队列研究，该研究包括 AET 配药数据。纳入诊断为首发非转移性乳腺癌且诊断后 12 个月内至少有 1 例 AET 配药的女性。采用基于组的轨迹建模，通过对每月 AET 配发的相似模式进行聚类，识别粘附轨迹组。使用多项 logistic 回归确定与轨迹相关的因素。 结果: 在 674 名妇女中，确定了 5 个 AET 依从性轨迹组 :( 1) 快速下降和停止 (5.2% 的妇女); (2) 中度下降和停止 (6.4%); (3) 缓慢下降 (17.2%); (4) 高粘附性 (30.0%); 和 (5) 保持非常高的粘附性(41.2%)。根据轨迹，平均 5 年覆盖天数比例从 10 到 97% 不等。没有接受化疗或个性化护理计划的女性更可能属于 AET 依从性下降和停止的轨迹。 结论: 我们的结果提供了纵向 AET 依从性模式的多样性、下降和停药的时间以及相关因素的信息，可以为医疗保健专业人员提供信息。
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.