INDIVIDUALIZED TX OF BREAST CANCER BASED ON TUMOR MOLECULAR CHARACTERISTICS

基于肿瘤分子特征的乳腺癌个体化治疗

• 批准号: 7378275
• 负责人: Silvia C. Formenti
• 金额: $ 2.06万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378275
• 关键词: INDIVIDUALIZED; TX; BREAST; CANCER; BASED

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Locally advanced breast cancer (LABC), defined as a tumor 5 cm or one which shows chest wall or skin involvement, has become rare in the general population of individuals with reasonable health care. However, in the under-served population it remains relatively common. Current therapy consists of pre-operative biopsy then pre-operative chemotherapy followed by excision of the tumor. This allows the tumor-specific markers to be discovered and the effectiveness of the chemotherapy regimen to be assessed. Experience suggests that the pathological response of the tumor to the primary chemotherapy can be used as a surrogate endpoint for survival: for a group, the "better" the initial treatment the better the survival measures of overall survival (OS) and disease-free survival (DFS). Adding radiation as part of the initial treatment helps improve the response to initial treatment locally to complement the effects of chemotherapy with 5-FU to kill micrometastatic disease elsewhere in the body, as these investigators have shown previously. Correlation with pretreatment biopsy showed that p53 over-expression was the only independent predictive factor for pathological response consistent with the poor performance of 5-FU with such disease. In the case of tissue that over-expresses p53, taxanes are a better choice. Treatment of tumors positive for HER-2/neu is improved with the addition of Trastuzumab to the regimen. These observations led to the current study. With the goal of maximizing the response to the initial treatment, and therefore of maximizing measures of survival, patients will be sorted into 4 groups depending on whether their tumors are positive or not for p53 and positive or not for HER-2/neu. p53-negative tumors will be treated with Capecitabine and p53-positive with Paclitaxel. HER-2/neu-positive tumors will be treated with Trastuzumab. All patients will receive radiotherapy. This study brings the state-of-the-art in anti-cancer treatment to a group of people who are typically underserved within the community. The investigators have developed this protocol fully to employ earlier studies of similar populations with this disease and stage. The study will test the feasibility of managing treatments targeting specific tumor characteristics and will allow a comparison with the results of earlier trials where targeting was not employed. Secondary objectives will be to accumulate core biopsies before and after treatment and to look at quality of life. However, this is a trial where targeted treatment is being used with drugs that are expected to make a difference. This makes this trial unusual and valuable. Thus far, patient outcomes have conformed with expectations.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。局部晚期乳腺癌 (LABC) 定义为 5 厘米的肿瘤或显示胸壁或皮肤受累的肿瘤，在拥有合理医疗保健的普通人群中已变得罕见。然而，在服务不足的人群中，这种情况仍然相对常见。目前的治疗包括术前活检、术前化疗、随后切除肿瘤。这使得可以发现肿瘤特异性标记物并评估化疗方案的有效性。 经验表明，肿瘤对主要化疗的病理反应可以用作生存的替代终点：对于一个组来说，初始治疗“越好”，总生存（OS）和无病生存（DFS）的生存衡量指标就越好。正如这些研究人员之前所表明的，在初始治疗中添加放射治疗有助于改善局部初始治疗的反应，以补充 5-FU 化疗的效果，从而杀死体内其他部位的微转移性疾病。与治疗前活检的相关性表明，p53 过度表达是病理反应的唯一独立预测因素，与 5-FU 在此类疾病中的不良表现一致。对于过度表达 p53 的组织，紫杉烷是更好的选择。在治疗方案中添加曲妥珠单抗可改善 HER-2/neu 阳性肿瘤的治疗。这些观察导致了当前的研究。为了最大限度地提高对初始治疗的反应，从而最大限度地提高生存率，根据患者的肿瘤 p53 是否阳性以及 HER-2/neu 是否阳性，将患者分为 4 组。 p53 阴性肿瘤将用卡培他滨治疗，p53 阳性肿瘤将用紫杉醇治疗。 HER-2/neu 阳性肿瘤将用曲妥珠单抗治疗。所有患者都将接受放射治疗。这项研究为社区内通常得不到充分服务的人群带来了最先进的抗癌治疗。研究人员完全开发了该方案，以利用对患有这种疾病和阶段的类似人群的早期研究。该研究将测试针对特定肿瘤特征进行治疗的可行性，并将与早期未采用靶向治疗的试验结果进行比较。次要目标是在治疗前后积累核心活检并观察生活质量。然而，这是一项靶向治疗与预计会产生影响的药物一起使用的试验。这使得这次试验不同寻常且有价值。到目前为止，患者的治疗结果符合预期。