Formenti Silvia C, Spicer Darcy, Skinner Kristin, Cohen Deidre, Groshen Susan, Bettini Anna, Naritoku Wesley, Press Michael, Salonga Dennis, Tsao-Wei Denice, Danenberg Kathy, Danenberg Peter
Radiation Oncology and Medicine, New York University School of Medicine, New York, NY 10016, USA.
Int J Radiat Oncol Biol Phys. 2002 Feb 1;52(2):397-405. doi: 10.1016/s0360-3016(01)02655-4.
The objective of this study was twofold: first, to identify patients with locally advanced breast cancer (LABC) who will achieve a pathological response to a preoperative regimen of concurrent paclitaxel and radiation; and second, to explore associations between molecular markers from the original tumors and pathological response.
Patients with previously untreated LABC were eligible to receive a regimen of preoperative concurrent paclitaxel, 30 mg/m(2) twice a week for a total of 8 weeks, and radiation delivered Weeks 2--6, 45 Gy at 1.8 Gy per fraction to the breast, ipsilateral axilla, and supraclavicular nodes. At mastectomy, pathologic findings were classified as pathological complete response (pCR) = no residual invasive cells in the breast and axillary contents; pathological partial response (pPR) = presence of < or = 10 microscopic foci of invasive cells; no pathological response (pNR) = pathological persistence of tumor. For each patient, pretreatment breast cancer biopsies were prospectively analyzed by immunohistochemistry (IHC) for estrogen and progesterone (ER/PR) hormonal receptors, HER2/neu and p53 overexpression. Estrogen receptor (ER), HER2/neu, metablastin, beta-tubulin III and IV, microtubule-associated protein-4 (MAP-4), bcl-2, bax, and cyclooxygenase-2 (COX-2) gene expression were measured using real-time quantitative polymerase chain reaction (PCR).
A total of 36 patients had pretreatment biopsies and were evaluable for the analysis of the association of molecular markers with pathological response. Pathological response in the mastectomy specimen was achieved in 12 of these 36 patients (33%). Only HER2/neu and ER gene expression were found to be significantly associated with the extent of pathological response to the regimen, i.e., tumors with low HER2/neu gene expression and negative estrogen receptors were more likely to respond to the tested regimen (p = 0.009 and p = 0.006, respectively). Conversely, p53 protein expression measured by IHC did not appear to be associated with pathological response (p = 0.67).
Further studies in LABC should assess whether patient selection for treatment based on the original tumor molecular characteristics could affect their chance to achieve a pathological response.
本研究的目的有两个：第一，识别局部晚期乳腺癌（LABC）患者中那些对术前紫杉醇与放疗联合方案有病理反应的患者；第二，探索原发肿瘤的分子标志物与病理反应之间的关联。
既往未接受治疗的LABC患者符合接受术前联合治疗方案的条件，该方案为紫杉醇30mg/m²，每周两次，共8周，放疗在第2至6周进行，乳腺、同侧腋窝和锁骨上淋巴结每次1.8Gy，共45Gy。在乳房切除术中，病理结果分类为病理完全缓解（pCR）=乳房和腋窝内容物中无残留浸润性细胞；病理部分缓解（pPR）=存在≤10个浸润性细胞的微小病灶；无病理反应（pNR）=肿瘤病理持续存在。对于每位患者，术前乳腺癌活检标本前瞻性地通过免疫组织化学（IHC）分析雌激素和孕激素（ER/PR）激素受体、HER2/neu和p53过表达情况。使用实时定量聚合酶链反应（PCR）测量雌激素受体（ER）、HER2/neu、转化生长因子β、β-微管蛋白III和IV、微管相关蛋白-4（MAP-4）、bcl-2、bax和环氧合酶-2（COX-2）基因表达。
共有36例患者进行了术前活检，可评估分子标志物与病理反应的关联。这36例患者中有12例（33%）在乳房切除标本中实现了病理反应。仅发现HER2/neu和ER基因表达与该方案的病理反应程度显著相关，即HER2/neu基因表达低且雌激素受体阴性的肿瘤对测试方案更可能有反应（分别为p = 0.009和p = 0.006）。相反，通过IHC测量的p53蛋白表达似乎与病理反应无关（p = 0.67）。
LABC的进一步研究应评估基于原发肿瘤分子特征进行治疗的患者选择是否会影响其获得病理反应的机会。
