TRIAL COMPARING ADJUVANT CLODRONATE THERAPY VERSUS PLACEBO EARLY BREAST CANCER

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。细胞毒性药物和激素的全身治疗已被证明可以延缓复发，并提高所有乳腺癌妇女的生存率。尽管取得了这些成功，但超过三分之一的乳腺癌患者最终可能会复发。骨是一个常见的复发部位，（单独或与其他部位合并）占最初复发部位的四分之一到三分之一，在频率上仅次于局部区域复发作为第一部位。大约三分之一发生骨转移的患者在其他部位也有疾病。在这些复发的患者中，随着疾病的进展，几乎70%的患者出现骨转移的影像学证据，并伴有骨折、疼痛和高钙血症等临床后遗症。淋巴结阳性患者的骨复发率高于淋巴结阴性患者，er阳性患者的骨复发率高于er阴性患者，尽管er阳性患者的整体远端复发率低于er阴性患者。因此，骨转移是乳腺癌患者发病和死亡的主要原因。该研究的目的是：1)确定对早期乳腺癌患者单独或在辅助化疗和/或激素治疗的基础上给予氯膦酸盐3年是否会提高无病生存率；2)确定氯膦酸钠是否会降低骨骼转移发生率、提高总生存率、提高无复发生存率、降低非骨骼转移发生率、降低骨骼发病率（骨骼骨折、高钙血症、骨骼疼痛、需要放射治疗、脊髓压迫）；3)探讨骨转换血清标志物作为骨转移发生的预后因素的相关性。

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. Systemic therapy with cytotoxic drugs and hormones has been shown to delay relapse and to improve survival in all groups of women with breast cancer. Despite these successes, more than one-third of women with carcinoma of the breast may eventually relapse. Bone is a common site of relapse, accounting (either alone or concomitantly with other sites) for one-quarter to one-third of initial sites of relapse and is second in frequency only to loco-regional recurrence as a first site. Approximately 1/3 of all patients who develop bone metastasis also have disease at other sites. Among those patients that recur, as the disease progresses, almost 70% develop radiological evidence of bone metastases with the attendant clinical sequelae of fracture, pain, and hypercalcemia occurring in the majority. Node-positive patients had higher rates of bone recurrence than did node-negative patients, and ER-positive patients had higher rates of bone recurrence than ER-negative patients, despite ER-positive patients having a lower rate of overall distant recurrence than did ER-negative patients. Bone metastases are, therefore, a major cause of morbidity and mortality in women with carcinoma of the breast. The study aims are to: 1) determine whether clodronate administered for three years either alone or in addition to adjuvant chemotherapy and/or hormonal therapy, in patients with early-stage breast cancer will improve disease-free survival; 2) determine whether clodronate will reduce the incidence of skeletal metastases, improve overall survival, improve relapse-free survival, reduce the incidence of non-skeletal metastases, and reduce the incidence of skeletal morbidity (skeletal fractures, hypercalcemia, skeletal pain, need for radiation therapy, spinal cord compression); and 3) investigate the relevance of serum markers of bone turnover as a prognostic factor for the development of bone metastasis.