Hoffman Robert M, Tanino Hirokazu
AntiCancer Inc., San Diego, CA, USA.
Department of Surgery, University of California, San Diego, CA, USA.
Methods Mol Biol. 2018;1760:93-100. doi: 10.1007/978-1-4939-7745-1_10.
The histoculture drug response assay (HDRA) was used to compare drug sensitivity of recurrent and primary breast cancer in vitro as well as in the clinic. The HDRA utilizes 3-dimensional culture of human tumors on Gelfoam. The evaluation rate was 98.8%. The HDRA mean inhibition rate of primary tumors vs. recurrent tumors was, respectively, 57.9% and 38.6% for doxorubicin (DOX); 59.9% and 42.8% for mitomycin C (MMC); 49.0% and 33.4% for 5-fluorouracil (5-FU); and 34.5% and 16.0% for cisplatinum (CDDP). The recurrent cases were pretreated clinically with CAF (cyclophosphamide [CTX], DOX, and 5-FU), CEF (CTX, epirubicin [EPN], and 5-FU), or CMF (CTX, methotrexate [MTX], and 5-FU). 64.7% of the recurrent cases were resistant to all four agents tested compared to 27% of the primary cases. Only 5.9% of the recurrent cases were sensitive to three or more agents as opposed to 18% of the primary cases. The correlation of the HDRA results to clinical outcome in another breast-cancer study was 80.0% with 15 cases evaluated consisting of five true positives, three false positives, seven true negatives, and no false negatives. HDRA was also performed on surgical specimens of primary tumor and axillary lymph node metastasis from each of 30 breast cancer patients. The lymph-node metastases were more resistant than the primary tumor for DOX, 5-FU, and MMC, but not for CDDP. The data suggest that both primary tumor and metastases from individual patients should be tested in the HDRA to enhance clinical efficacy of chemotherapy. There also was a lack of correlation with breast cancer subtype and drug response in the HDRA, further suggesting the importance of individualized treatment for breast cancer patients afforded by the HDRA.
组织培养药物反应测定法（HDRA）用于在体外以及临床中比较复发性和原发性乳腺癌的药物敏感性。HDRA利用明胶海绵上的人肿瘤三维培养。评估率为98.8%。HDRA中，原发性肿瘤与复发性肿瘤的平均抑制率分别为：阿霉素（DOX）为57.9%和38.6%；丝裂霉素C（MMC）为59.9%和42.8%；5-氟尿嘧啶（5-FU）为49.0%和33.4%；顺铂（CDDP）为34.5%和16.0%。复发病例临床上预先接受了CAF（环磷酰胺[CTX]、DOX和5-FU）、CEF（CTX、表柔比星[EPN]和5-FU）或CMF（CTX、甲氨蝶呤[MTX]和5-FU）治疗。64.7%的复发病例对所有四种测试药物耐药，而原发性病例中这一比例为27%。只有5.9%的复发病例对三种或更多药物敏感，而原发性病例中这一比例为18%。在另一项乳腺癌研究中，HDRA结果与临床结局的相关性为80.0%，评估了15例病例，包括5例假阳性、3例假阴性、7例真阴性和无假阴性。对30例乳腺癌患者的原发性肿瘤和腋窝淋巴结转移的手术标本也进行了HDRA。对于DOX、5-FU和MMC，淋巴结转移比原发性肿瘤更耐药，但对CDDP并非如此。数据表明，在HDRA中应检测个体患者的原发性肿瘤和转移灶，以提高化疗的临床疗效。HDRA中也缺乏与乳腺癌亚型和药物反应的相关性，这进一步表明了HDRA为乳腺癌患者提供个体化治疗的重要性。
