新辅助化疗后高危早期乳腺癌骨髓中播散肿瘤细胞的结果和临床病理特征：I-SPY SURMOUNT 研究。
Outcomes and clinicopathologic characteristics associated with disseminated tumor cells in bone marrow after neoadjuvant chemotherapy in high-risk early stage breast cancer: the I-SPY SURMOUNT study.
机构信息
University of California San Francisco, San Francisco, CA, USA.
University of Pennsylvania, Philadelphia, PA, USA.
出版信息
Breast Cancer Res Treat. 2023 Apr;198(2):383-390. doi: 10.1007/s10549-022-06803-0. Epub 2023 Jan 23.
PURPOSE
Disseminated tumor cells (DTCs) expressing epithelial markers in the bone marrow are associated with recurrence and death, but little is known about risk factors predicting their occurrence. We detected EPCAM+/CD45- cells in bone marrow from early stage breast cancer patients after neoadjuvant chemotherapy (NAC) in the I-SPY 2 Trial and examined clinicopathologic factors and outcomes.
METHODS
Patients who signed consent for SURMOUNT, a sub-study of the I-SPY 2 Trial (NCT01042379), had bone marrow collected after NAC at the time of surgery. EPCAM+CD45- cells in 4 mLs of bone marrow aspirate were enumerated using immunomagnetic enrichment/flow cytometry (IE/FC). Patients with > 4.16 EPCAM+CD45- cells per mL of bone marrow were classified as DTC-positive. Tumor response was assessed using the residual cancer burden (RCB), a standardized approach to quantitate the extent of residual invasive cancer present in the breast and the axillary lymph nodes after NAC. Association of DTC-positivity with clinicopathologic variables and survival was examined.
RESULTS
A total of 73 patients were enrolled, 51 of whom had successful EPCAM+CD45- cell enumeration. Twenty-four of 51 (47.1%) were DTC-positive. The DTC-positivity rate was similar across receptor subtypes, but DTC-positive patients were significantly younger (p = 0.0239) and had larger pretreatment tumors compared to DTC-negative patients (p = 0.0319). Twenty of 51 (39.2%) achieved a pathologic complete response (pCR). While DTC-positivity was not associated with achieving pCR, it was significantly associated with higher RCB class (RCB-II/III, 62.5% vs. RCB-0/I; 33.3%; Chi-squared p = 0.0373). No significant correlation was observed between DTC-positivity and distant recurrence-free survival (p = 0.38, median follow-up = 3.2 years).
CONCLUSION
DTC-positivity at surgery after NAC was higher in younger patients, those with larger tumors, and those with residual disease at surgery.
目的
骨髓中表达上皮标志物的播散性肿瘤细胞（DTCs）与复发和死亡相关，但对于预测其发生的危险因素知之甚少。我们在 I-SPY 2 试验中检测了新辅助化疗（NAC）后早期乳腺癌患者骨髓中的 EPCAM+/CD45-细胞，并检查了临床病理因素和结局。
方法
签署了 I-SPY 2 试验 SURMOUNT 子研究（NCT01042379）同意书的患者在手术时采集 NAC 后骨髓。使用免疫磁珠富集/流式细胞术（IE/FC）对 4ml 骨髓抽吸物中的 EPCAM+CD45-细胞进行计数。将骨髓中每毫升 EPCAM+CD45-细胞数大于 4.16 的患者分类为 DTC 阳性。使用残留肿瘤负荷（RCB）评估肿瘤反应，这是一种标准化方法，用于定量 NAC 后乳房和腋窝淋巴结中残留浸润性癌的程度。检查 DTC 阳性与临床病理变量和生存的关系。
结果
共纳入 73 例患者，其中 51 例成功进行了 EPCAM+CD45-细胞计数。51 例中有 24 例（47.1%）为 DTC 阳性。受体亚型之间的 DTC 阳性率相似，但 DTC 阳性患者明显较年轻（p=0.0239），且治疗前肿瘤较大（p=0.0319）。51 例中有 20 例（39.2%）达到病理完全缓解（pCR）。虽然 DTC 阳性与达到 pCR 无关，但与更高的 RCB 分级（RCB-II/III，62.5% vs. RCB-0/I；33.3%；卡方检验 p=0.0373）显著相关。DTC 阳性与远处无复发生存率无显著相关性（p=0.38，中位随访 3.2 年）。
结论
NAC 后手术时 DTC 阳性率在年轻患者、肿瘤较大的患者和手术时残留疾病的患者中更高。
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