INDIVIDUALIZED TX OF BREAST CANCER BASED ON TUMOR MOLECULAR CHARACTERISTICS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。局部晚期乳腺癌（LABC），定义为肿瘤5厘米或一个显示胸壁或皮肤累及，已成为罕见的个人合理的医疗保健的一般人群。然而，在服务不足的人群中，它仍然相对普遍。目前的治疗方法包括术前活检，然后术前化疗，最后切除肿瘤。这使得肿瘤特异性标记物得以发现，化疗方案的有效性得以评估。经验表明，肿瘤对初始化疗的病理反应可作为生存期的替代终点：对于一组患者，初始治疗越“好”，总生存期（OS）和无病生存期（DFS）的生存指标越好。正如这些研究人员之前所表明的那样，在初始治疗中加入放疗有助于改善局部对初始治疗的反应，以补充5-FU化疗的效果，杀死身体其他部位的微转移性疾病。与预处理活检的相关性显示，p53过表达是唯一独立的预测病理反应的因素，这与5-FU治疗这种疾病的不良表现一致。在过度表达p53的组织中，紫杉烷是更好的选择。HER-2/neu阳性肿瘤的治疗随着曲妥珠单抗的加入而得到改善。这些观察结果导致了目前的研究。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，HER-2/neu是否阳性，将患者分为4组。p53阴性肿瘤用卡培他滨治疗，p53阳性肿瘤用紫杉醇治疗。HER-2/新阳性肿瘤将使用曲妥珠单抗治疗。所有患者将接受放射治疗。这项研究将最先进的抗癌治疗带给了一群在社区中通常得不到充分服务的人。研究人员制定了这一方案，充分利用了早期对患有这种疾病和阶段的类似人群的研究。该研究将测试针对特定肿瘤特征的管理治疗的可行性，并将与未采用靶向治疗的早期试验结果进行比较。次要目标将是积累治疗前后的核心活检，并观察生活质量。然而，这是一项将靶向治疗与预期会产生影响的药物结合使用的试验。这使得这次审判不同寻常且有价值。到目前为止，患者的结果与预期相符。

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.