自 2000 年以来，年轻乳腺癌患者的分期特异性生存率有所改善: 但并非平等。
- 作者列表："Trewin CB","Johansson ALV","Hjerkind KV","Strand BH","Kiserud CE","Ursin G
PURPOSE:The stage-specific survival of young breast cancer patients has improved, likely due to diagnostic and treatment advances. We addressed whether survival improvements have reached all socioeconomic groups in a country with universal health care and national treatment guidelines. METHODS:Using Norwegian registry data, we assessed stage-specific breast cancer survival by education and income level of 7501 patients (2317 localized, 4457 regional, 233 distant and 494 unknown stage) aged 30-48 years at diagnosis during 2000-2015. Using flexible parametric models and national life tables, we compared excess mortality up to 12 years from diagnosis and 5-year relative survival trends, by education and income as measures of socioeconomic status (SES). RESULTS:Throughout 2000-2015, regional and distant stage 5-year relative survival improved steadily for patients with high education and high income (high SES), but not for patients with low education and low income (low SES). Regional stage 5-year relative survival improved from 85 to 94% for high SES patients (9% change; 95% confidence interval: 6, 13%), but remained at 84% for low SES patients (0% change; - 12, 12%). Distant stage 5-year relative survival improved from 22 to 58% for high SES patients (36% change; 24, 49%), but remained at 11% for low SES patients (0% change; - 19, 19%). CONCLUSIONS:Regional and distant stage breast cancer survival has improved markedly for high SES patients, but there has been little survival gain for low SES patients. Socioeconomic status matters for the stage-specific survival of young breast cancer patients, even with universal health care.
目的: 年轻乳腺癌患者的阶段特异性生存率有所改善，可能是由于诊断和治疗的进步。我们讨论了在一个有全民医疗保健和国民治疗指南的国家，生存改善是否已经达到所有社会经济群体。 方法: 使用挪威注册数据，我们通过教育和收入水平评估了 7501 例患者的分期特异性乳腺癌生存率 (2317 为本地化，4457 为区域性，233 为远距离，494 为未知阶段) 2000-2015 期间诊断时年龄 30-48 岁。使用灵活的参数模型和国民生命表，我们比较了从诊断到 12 年的超额死亡率和 5 年相对生存趋势，按教育和收入作为社会经济地位 (SES) 的衡量标准。 结果: 在整个 2000-2015 期间，高教育和高收入 (高 SES) 患者的区域和远期 5 年相对生存率稳步提高,但不适用于低教育和低收入 (低 SES) 患者。高 SES 患者的区域阶段 5 年相对生存率从 85 提高到 94% (9% 变化; 95% 置信区间: 6，13%),但低 SES 患者仍保持在 84% (0% 变化;-12%)。高 SES 患者的远处阶段 5 年相对生存率从 22 提高到 58% (变化 36%; 24，49%)，但低 SES 患者保持在 11% (变化 0%;-19, 19%)。 结论: 高 SES 患者的区域和远期乳腺癌生存率显著提高，但低 SES 患者的生存收益甚微。社会经济地位对年轻乳腺癌患者的阶段特异性生存至关重要，即使有全民医疗保健。
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.