Schneider J, Lucas R, Sánchez J, Ruibal A, Tejerina A, Martín M
Fundación Tejerina-Centro de Patología de la Mama, Madrid, Spain.
Anticancer Res. 2000 Nov-Dec;20(6B):4373-7.
To assess if molecular markers are able to predict the response to induction chemotherapy in locally advanced breast cancer, and if any variation in their expression is associated with the degree of axillary lymph node invasion.
Between 1995 and 1999, 48 patients with locally advanced breast cancer were submitted to induction chemotherapy at Fundación Tejerina--Centro de Patología de la Mama, Madrid, Spain. The patients carried either tumors larger than 5 cm in diameter with clinically positive axillary nodes, T4a or T4b tumors regardless of size, or inflammatory carcinomas. All received between 3 and 6 cycles of CAF standard polychemotherapy (Cyclophosphamide, Doxorubicin and 5-Fluorouracil) with the exception of one patient, who received CMF therapy (Cyclophosphamide, Methotrexate and 5-Fluorouracil), and another one, who received Taxotere-Doxorubicin. After completion of their induction chemotherapy scheme, 1 patient showed a "complete clinical response" (CCR, with disappearance of all clinical and radiological signs of tumor presence), 36 (75.0%) patients showed a "partial response" (PR, > 50%), 10 (20.8%) showed "no response" (NR, < 50%), and finally one progressed under treatment. Core biopsies were performed in all cases prior to treatment for histological diagnosis which allowed for the determination of the following parameters by means of immunohistochemistry: hormone receptors (ER and PR), oncogenes and tumor suppressor genes (c-erb-B2 and p53) and the proliferation marker Ki67. Initial tumor size, histologic and nuclear grade and histologic variety were also included as variables of the study. After chemotherapy, 37 patients were submitted to a rescue mastectomy at our center. The same aforementioned parameters were determined once again on the operative specimen, together with MDR1 expression (using two different antibodies) and LRP expression. As outcome variables, objective response to treatment and the presence of invaded axillary nodes were considered.
Only the expression of the proliferation-associated Ki67 antigen, as well as nuclear grade were affected significantly (p < 0.05) by the previous chemotherapeutic treatment. All other studied parameters showed no significant change in expression. More disappointingly, even, none of the studied variables showed any significant power for predicting either an objective response to treatment, or the presence of invaded axillary nodes at surgery. Both outcome end-points were also unrelated to each other. Overexpression of the multidrug-resistance gene or the LRP gene, finally, showed no correlation whatsoever with the previous response to chemotherapy.
According to these results, the parameters employed by us are of no practical use for predicting the response to treatment or the presence of invaded nodes at rescue surgery in locally advanced breast cancer. Clinical and surgical assessment remain thus the mainstay of treatment for this group of patients.
评估分子标志物是否能够预测局部晚期乳腺癌对诱导化疗的反应，以及其表达的任何变化是否与腋窝淋巴结侵犯程度相关。
1995年至1999年间，48例局部晚期乳腺癌患者在西班牙马德里Fundación Tejerina - 乳腺病理学中心接受诱导化疗。这些患者所患肿瘤要么直径大于5 cm且腋窝淋巴结临床阳性，要么是T4a或T4b肿瘤（无论大小），要么是炎性癌。除1例接受CMF方案（环磷酰胺、甲氨蝶呤和5-氟尿嘧啶）化疗，另1例接受多西他赛-阿霉素化疗外，所有患者均接受3至6个周期的CAF标准联合化疗（环磷酰胺、阿霉素和5-氟尿嘧啶）。在完成诱导化疗方案后，1例患者显示“完全临床缓解”（CCR，所有肿瘤存在的临床和放射学迹象均消失），36例（75.0%）患者显示“部分缓解”（PR，> 50%），10例（20.8%）显示“无反应”（NR，< 50%），最后1例在治疗过程中病情进展。所有病例在治疗前均进行了核心活检以进行组织学诊断，这使得能够通过免疫组织化学确定以下参数：激素受体（ER和PR）、癌基因和肿瘤抑制基因（c-erb-B2和p53）以及增殖标志物Ki67。初始肿瘤大小、组织学和核分级以及组织学类型也作为研究变量纳入。化疗后，37例患者在本中心接受了挽救性乳房切除术。在手术标本上再次确定上述相同参数，以及MDR1表达（使用两种不同抗体）和LRP表达。作为结果变量，考虑治疗的客观反应和腋窝淋巴结受侵情况。
只有增殖相关的Ki67抗原的表达以及核分级受到先前化疗的显著影响（p < 0.05）。所有其他研究参数的表达均未显示出显著变化。更令人失望的是，所研究的变量均未显示出对预测治疗的客观反应或手术时腋窝淋巴结受侵情况有任何显著作用。这两个结果终点彼此之间也无关联。最后，多药耐药基因或LRP基因的过表达与先前的化疗反应没有任何相关性。
根据这些结果，我们所采用的参数对于预测局部晚期乳腺癌的治疗反应或挽救性手术时淋巴结受侵情况没有实际用途。因此，临床和手术评估仍然是这组患者治疗的主要依据。
