Mammostrat® as a tool to stratify breast cancer patients at risk of recurrence during endocrine therapy
Mammostrat® as a tool to stratify breast cancer patients at risk of recurrence during endocrine therapy
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DOI：
10.1186/bcr2604
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发表时间：
2010-01-01
影响因子：
7.4
通讯作者：
Chetty, Udi
中科院分区：
文献类型：
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作者：
Bartlett, John M. S.;Thomas, Jeremy;Chetty, Udi
早期乳腺癌患者，接受内分泌治疗，有大约90%的5年无病生存率。然而，对于复发风险较高的患者，尽管内分泌治疗，可能需要额外的辅助治疗，如化疗。挑战在于前瞻性地识别这样的患者。乳房造影(R)测试使用五种免疫组织化学标记物将接受他莫昔芬治疗的患者分为危险组，为治疗决策提供信息。我们在单一中心接受保乳手术和长期随访的混合人群中测试了该小组的疗效。方法：在适当的伦理审查后，收集了连续系列（1981年至1998年）1,812名接受广泛局部切除和术后放疗的妇女的组织微阵列。在1390例染色病例中，197例未接受辅助激素治疗或化疗，1044例仅接受他莫昔芬治疗，149例接受激素治疗和化疗联合治疗。诊断时中位年龄为57岁，绝经后71%，淋巴结阳性23.9%，中位肿瘤大小为1.5 cm。使用3个0.6 mm(2)的组织芯片对样本进行染色，并评估p53、HTF9C、CEACAM5、NDRG1和SLC7A5的阳性。对每个病例进行乳房造影(R)风险评分，并通过标志物阳性和风险评分分析远处无复发生存期（DRFS）、无复发生存期（RFS）和总生存期（OS）。结果：雌激素受体（ER）阳性乳腺癌的R评分升高与DRFS、RFS和OS降低显著相关（P < 0.00001）。多因素分析中，DRFS、RFS和OS的风险评分与常规危险因素无关（P < 0.05）。在淋巴结阴性、他莫昔芬治疗的患者中，低危组10年复发率为7.6 +/- 1.5%，高危组为20.0 +/- 4.4%。此外，探索性分析揭示了er阴性和未治疗患者预后的相关性。结论：这是第五项提供证据的独立研究，证明乳房造影(R)可以作为er阳性、他莫昔芬治疗的乳腺癌的独立预后工具。此外，本研究首次揭示了与淋巴结状态和er阴性肿瘤无关的预后的可能关联。在之前的结果背景下，这些数据进一步支持抗体小组作为早期乳腺癌患者管理的辅助手段。
Introduction: Patients with early-stage breast cancer, treated with endocrine therapy, have approximately 90% 5-year disease-free survival. However, for patients at higher risk of relapse despite endocrine therapy, additional adjuvant therapy, such as chemotherapy, may be indicated. The challenge is to prospectively identify such patients. The Mammostrat (R) test uses five immunohistochemical markers to stratify patients on tamoxifen therapy into risk groups to inform treatment decisions. We tested the efficacy of this panel in a mixed population of cases treated in a single center with breast-conserving surgery and long-term follow-up.Methods: Tissue microarrays from a consecutive series (1981 to 1998) of 1,812 women managed by wide local excision and postoperative radiotherapy were collected following appropriate ethical review. Of 1,390 cases stained, 197 received no adjuvant hormonal or chemotherapy, 1,044 received tamoxifen only, and 149 received a combination of hormonal therapy and chemotherapy. Median age at diagnosis was 57, 71% were postmenopausal, 23.9% were node-positive and median tumor size was 1.5 cm. Samples were stained using triplicate 0.6 mm(2) tissue microarray cores, and positivity for p53, HTF9C, CEACAM5, NDRG1 and SLC7A5 was assessed. Each case was assigned a Mammostrat (R) risk score, and distant recurrence-free survival (DRFS), relapse-free survival (RFS) and overall survival (OS) were analyzed by marker positivity and risk score.Results: Increased Mammostrat (R) scores were significantly associated with reduced DRFS, RFS and OS in estrogen receptor (ER)-positive breast cancer (P < 0.00001). In multivariate analyses the risk score was independent of conventional risk factors for DRFS, RFS and OS (P < 0.05). In node-negative, tamoxifen-treated patients, 10-year recurrence rates were 7.6 +/- 1.5% in the low-risk group versus 20.0 +/- 4.4% in the high-risk group. Further, exploratory analyses revealed associations with outcome in both ER-negative and untreated patients.Conclusions: This is the fifth independent study providing evidence that Mammostrat (R) can act as an independent prognostic tool for ER-positive, tamoxifen-treated breast cancer. In addition, this study revealed for the first time a possible association with outcome regardless of node status and ER-negative tumors. When viewed in the context of previous results, these data provide further support for this antibody panel as an aid to patient management in early-stage breast cancer.