ER阳性、HER2阴性、淋巴结阴性早期浸润性乳腺导管癌X线征象与Oncotype DX21基因检测结果间的相关性分析

背景 与目的:Oncotype DX21基因检测具有预后预测和辅助治疗决策的价值,但通过有创手术获取的检测样本无法完全表征肿瘤的整体情况,而乳腺X线摄影是一项无创、经济、操作简单的常规检查项目.若能找到影像标志物,则可以实现以非侵入方式获取相关基因表达量方面的信息,同样达到预测预后和复发风险概率的目的.探究雌激素受体(...     

Oncotype DX 21基因检测在ER阳性早期乳腺癌中的应用

在诸多评估雌激素受体(estrogen receptor,ER)阳性早期乳腺癌复发风险的多基因工具中,Oncotype DX 21基因检测因其独特的疗效预测作用而被广泛应用于淋巴结阴性患者.多项回顾性研究已证明其在淋巴结阳性人群同样具有预后预测价值,但前瞻性临床试验证据仍不充分.该检测能协同其他重要临床病理因素,影响乳腺癌患者的辅助治疗方案,且具较高的成本效益.该研究就21基因检测对早期乳腺癌患者的预后预测价值、独特优势、辅助治疗决策影响、成本效果和现存争议进行综述.     

21基因Oncotype Dx对乳腺癌预后研究的进展

目前最为有效的乳腺癌治疗模式是多学科综合标准化治疗。然而长期以来缺乏有效的预后预测手段来指导患者的个体化治疗,以至于相当一部分化疗获益甚少的低风险患者也不得不接受化疗。随着基因组学的发展,已有数个基因系列的检测结果被证实可以用于乳腺癌预后的预测,进而判断测患者从化疗中的获益,避免过度治疗。22基因Oncotype Dx检测正是其中之一,其有效性及准确性己在各种临床研究中得到了征实。水文就21基因Oncotype Dx对乳腺痛预后研究的进展进行综述。     

乳腺癌21基因检测的研究进展

乳腺癌是一类具有异质性的肿瘤,不同患者的治疗方法和疗效都不相同。尽管目前仍在努力为激素受体（hormone receptor,HR）阳性（+）、人表皮生长因子受体2（human epidermal growth factor receptor 2,HER-2）阴性（-）、淋巴结（axillary lymph node,ALN）阴性（-）的早期乳腺癌患者寻找合适的治疗方法,但其术后是否需要化疗仍然是肿瘤科医生面临的一个难题。以往治疗主要依赖于经典的组织病理学和免疫组织化学技术,随着精准医疗时代的到来,我们需要更定量的诊断方法和合理的个体化治疗。虽然化疗可降低疾病复发风险并提高生存率,但它带来的不良反应事件会降低患者的生活质量,尤其低复发风险（recurrence risk,RS)有可能超过化疗益处。21基因检测不仅可以预测这类早期乳腺癌化疗疗效及评估预后,还可提供精准的个体化治疗方案指导用药,为患者增添信心。本文就乳腺癌21基因检测的研究进展进行综述。     

HR+、HER2-早期浸润性乳腺癌中多基因检测的应用及进展#br#

临床上激素受体（HR）阳性乳腺癌患者治疗方案的制定通常基于病理学的各项指标。然而,一些临床特征相似的患者在接受相同的治疗后,疗效和预后有很大差异,这提示经典的临床病理学特点可能不足以用来制定乳腺癌综合治疗策略。该文研究早期浸润性乳腺癌中HR阳性、人表皮生长因子受体2（HER2）阴性的人群,对3种常见的基因检测手段21基因复发评分（OncotypeDX）、70基因（MammaPrint）和PAM50（Prosigna）的临床有效性和实用性进行系统的综述。3种检测方式均能区分预后差异,可用于HR+、HER2-、淋巴结未受累的早期乳腺癌患者的全身治疗指导,MammaPrint还可用于1～3枚淋巴结受累的患者。Prosigna具有长期预后能力,或可用于筛选能从延长内分泌治疗中获益的人群。     

28基因检测在亚洲早期乳腺癌中的研究进展

乳腺癌是全球女性中最常见且死亡率最高的恶性肿瘤之一.随着分子生物学技术的发展,乳腺癌的诊疗模式也逐渐向精准化、个体化方向发展.目前临床应用较广泛的多基因检测包括Oncotype DX?、MammaPrint?等;然而这些检测技术均起源于欧美人群,在亚洲乳腺癌患者中的应用有限,对预后的评判价值有待考量.而28基因检测是第...     

Oncotype DX 21在乳腺癌预后中的作用

Oncotype DX21作为商业化的乳腺癌预后和预测生物学标志物，有望改变分子生物学标志物作为预后和预测因素还不尽人意的现状。现综述Oncotype DX21预后指标的建立及其作为预后和预测因素在乳腺癌中的意义。     

21基因在激素受体和淋巴结阳性早期乳腺癌治疗决策中的地位

随着乳腺癌早期诊断率的逐步提高,对激素受体阳性、淋巴结阴性的乳腺癌患者,运用21基因复发风险评分来决策治疗,已逐步被临床医师所接受,但其在激素受体阳性、淋巴结阳性的早期乳腺癌治疗中的地位仍在不断地探讨中。本文将通过对几个临床研究结果的分析,来阐述激素受体阳性、腋窝淋巴结阳性的早期乳腺癌复发评分结果对治疗决策的意义。     

Oncotype DX 21在乳腺癌预后中的作用

Oncotype DX 21作为商业化的乳腺癌预后和预测生物学标志物,有望改变分子生物学标志物作为预后和预测因素还不尽人意的现状。现综述Oncotype DX 21预后指标的建立及其作为预后和预测因素在乳腺癌中的意义。     

21基因检测对乳腺癌预测和预后的意义

激素阳性的早期乳腺癌患者术后是否需要化疗已成为临床肿瘤医生的一大挑战,21基因检测以RT-QPCR（实时定量荧光PCR）技术对乳腺癌石蜡包埋组织的增殖、侵袭、Her-2、激素等相关基因进行定量并进行复发评分,为乳腺癌的治疗选择、预后判断提供新依据.本文对国内外21基因检测（OncotypeDX）对乳腺癌预后/预测的研究进展进行综述.     

How Canadian Oncologists Use Oncotype DX for Treatment of Breast Cancer Patients

Background: The literature suggests that medical oncologists differ on how they use the Oncotype DX (ODX) genomic assay for making decisions about systemic therapy in breast cancer patients. Given the emergence of data supporting the use of genomic profiling for the prognosis and predicting benefit of chemotherapy, we surveyed medical oncologists in Canada to assess their usage and perception of the ODX assay. Methods: A 34-item survey was distributed to Canadian medical oncologists via the Canadian Association of Medical Oncologists. Data was collected on physician demographics, ODX usage patterns, and physicians’ perception of the impact clinical and pathologic characteristics make on ODX utilization. Results: Response rate was 20.6% with 47 responses received from 228 survey sent. Forty-five responses were eligible for analysis. Sixty-two percent (28/45) of respondents treated predominantly breast cancer, and 60% (27/45) have been in practice for at least 10 years. The most cited reason for using ODX was to avoid giving patients unnecessary chemotherapy (64%; 29/45). Sixty-seven percent (30/45) deferred making treatment decisions until ODX testing was completed. Factors most strongly impacting ODX utilization included: patient request, medical comorbidities and tumor grade. In clinical scenarios, ODX was more frequently selected for patients aged 40–65 (vs. <40 or >65), grade 2 tumors (vs. grade 1 or 3), and Ki-67 index of 10–20% (vs. <10% or >20%). Conclusions: This survey demonstrated that Canadian medical oncologists are preferentially using ODX to avoid giving patients unnecessary chemotherapy. The utilization of ODX is mainly in patients with intermediate clinical and pathologic features.     

Relationship Between Hereditary Cancer Syndromes and Oncotype DX Recurrence Score

BackgroundOncotype DX (ODX) is a genomic assay of tumor tissue that is utilized to predict the likelihood of recurrence and benefit of chemotherapy in breast cancer patients. Five to 10% of breast cancers are hereditary, and hereditary syndromes may not be uncovered through family history alone. We hypothesized that high ODX recurrence score (RS) may signal a potential hereditary cancer risk.Patients and MethodsWe performed a retrospective analysis of data from hormone receptor–positive breast cancer patients who had undergone ODX and germline genetic testing. The chi-square test and Fisher exact test were used to examine univariable association between RS and germline mutation status. Multivariable logistic regression was utilized to examine if there was an association of RS with germline mutation status.ResultsIn univariable analysis, the association of RS with germline mutation status was significant (P < .0001). In the multivariable logistic regression model predicting germline mutation status, RS level remained significantly associated with germline mutation, in particular BRCA1 or BRCA2. The mean RS for those with non-BRCA1/2 germline mutations versus those without germline mutations was not significant (P = .38).ConclusionHigh RS is associated with germline mutation status. Breast cancer patients with high RS are more likely to harbor a mutation in the BRCA1 or BRCA2 genes. If confirmed prospectively, oncologists may consider referring patients with high RS for genetic risk assessment and counseling to inform management plans, as well as counseling of family members.     

The impact of Oncotype DX testing on breast cancer management and chemotherapy prescribing patterns in a tertiary referral centre

IntroductionThe use of chemotherapy in node-negative, (O)Estrogen Receptor (ER)-positive breast cancer has changed significantly since the introduction of Oncotype DX to determine systemic recurrence risk based on tumour genomic signature.AimsThis study aims to

• 1.Document longitudinal changes in chemotherapy use,
• 2.Assess the impact of new evidence on local protocol.

MethodsA cohort study was undertaken, including consecutive patients with early node-negative, ER-positive breast cancer diagnosed between 2006 and May 2013, including a period of prospective clinical trial (Trial Assigning Individualised Options for Treatment (TAILORx)) recruitment. Data were collected regarding patient demographics, tumour clinico-pathological features, Oncotype DX use and recurrence score and chemotherapy use. All therapeutic decisions were made following multidisciplinary discussion, with adherence to guidelines and consideration of trial protocol and Oncotype DX recurrence scores.Results479 consecutive patients were included in the study, of whom 241 (50%) underwent Oncotype DX testing, 97 as part of the TAILORx clinical trial. Oncotype DX testing began on a trial basis in 2007 and until October 2011, only patients enrolled on TAILORx availed of genomic profiling. From October 2011, Oncotype DX was used in all eligible patients as per National Cancer Control Programme (NCCP) guidelines. A total of 216 (45%) patients received chemotherapy. The use of chemotherapy changed in inverse proportion to the availability of the genomic assay. Of those patients in whom Oncotype DX was utilised, 138 (57%) were spared chemotherapy.ConclusionThis study validates the use of molecular testing in the rationalisation of systemic therapy.     

Cost‐Effectiveness Analysis of Recurrence Score‐Guided Treatment Using a 21‐Gene Assay in Early Breast Cancer

Purpose.

Most guidelines for hormone receptor (HR)–positive early breast cancer recommend addition of adjuvant chemotherapy for most women, leading to overtreatment, which causes considerable morbidity and cost. There has been recent incorporation of gene expression analysis in aiding decision making. We evaluated the cost-effectiveness of recurrence score (RS)–guided treatment using 21-gene assay as compared with treatment guided by the Adjuvant! Online program (AOL).

Patients and Methods.

A Markov model was developed to compare the cost-effectiveness of treatment guided either by 21-gene assay or by AOL in a 50-year-old woman with lymph node–negative HR-positive breast cancer over a lifetime horizon. We assumed that women classified to be at high risk all received chemotherapy followed by tamoxifen and those classified to be at low risk received tamoxifen only. The model took a health care payer''s perspective with results reported in 2008 Canadian dollars ($). Event rates, costs, and utilities were derived from the literature. Both costs and benefits were discounted at 5%. Outcome measures were life years gained, quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs).

Results.

For a 50-year-old woman, RS-guided treatment was associated with an incremental lifetime cost of $4,102 and a gain in 0.065 QALY, with an ICER of $63,064 per QALY compared with AOL-guided treatment. ICER increased with increasing cost of 21-gene assay and increasing age of patients. Results were most sensitive to probabilities relating to risk categorization and recurrence rate.

Conclusions.

The 21-gene assay appears cost-effective from a Canadian health care perspective.     

Oncotype DX 21-gene test has a low recurrence score in both pure and mixed mucinous breast carcinoma

The Oncotype DX 21-gene test can be used to predict chemotherapy efficacy in patients with estrogen receptor (ER)-positive and HER2-negative breast cancer; however, the data on the 21-gene recurrence score (RS) for mucinous breast carcinoma (MBC) are limited. The present study aimed to evaluate the distribution pattern and clinical value of the 21-gene RS in patients with MBC. A total of 38 pure MBC (PMBC) and 11 mixed MBC (MMBC) cases were retrospectively analyzed, and a total of 29 ER-positive and HER2-negative MBCs underwent the Oncotype DX 21-gene test. There were no statistically significant differences between the PMBCs and MMBCs in age, tumor size and molecular subtype; however, patients with MMBC showed a significantly higher incidence rate of nodal metastases compared with that in patients with PMBC (72.7 vs. 16.2%, respectively). Following surgery, 87.8 and 59.2% of the enrolled patients received endocrine therapy and chemotherapy, respectively. With a median follow-up of 65.6 months, the 5-year disease-free survival and overall survival rates were 97.0 and 100.0%, respectively. The 21-gene test revealed that the proportions of patients with MBC categorized into low (RS <18), intermediate (RS ≥18-30) and high (RS ≥30) risk groups were 51.7, 44.8 and 3.5%, respectively, and there was no statistically significant difference between the PMBC and MMBC cases. Notably, among the genes in the 21-gene RS testing, the expression levels of cathepsin V, progesterone receptor (PR) and CD68 were significantly higher in the PMBC group compared with that in the MMBC group. In conclusion, the current study demonstrated that patients with MBC had a favorable prognosis, and both PMBC and MMBC cases had a low- and intermediate-risk RS, which suggests that a considerable proportion of patients may be able to avoid chemotherapy. In addition, the high expression level of PR, based on the 21-gene test in PMBCs, indicated that they may have a more favorable response to endocrine therapy than MMBCs.