Kurebayashi Junichi
Department of Breast and Thyroid Surgery, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan.
Breast Cancer. 2009;16(4):275-80. doi: 10.1007/s12282-009-0111-2. Epub 2009 May 1.
The intrinsic subtype has demonstrated that breast cancers can be classified into biologically and clinically meaningful subgroups. Most breast tumors categorized as one of the intrinsic subtypes, i.e., basal-like, have an estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor receptor 2-negative phenotype, so-called triple-negative (TN) phenotype; however, TN breast cancer is not a synonym for basal-like subtype. TN breast cancers account for 10-20% of all breast cancers, and are more biologically aggressive than breast cancers of other subgroups. Tailored therapies, such as endocrine therapy and anti-HER2 therapy, are not applicable to TN breast cancer. To develop novel strategies against TN breast cancer, it is essential to understand the specific pathways driving the aggressive behavior of TN breast cancer. Preclinical and clinical studies have suggested that DNA-damaging agents and poly ADP-ribose polymerase inhibitors are active in TN breast cancer harboring BRCA1 dysfunction; anti-epidermal growth factor receptor (EGFR) antibodies and EGFR tyrosine kinase inhibitors are active in TN breast cancer with EGFR gene amplification; dasatinib is active in TN breast cancer with activated Src tyrosine kinases; inhibitors of a mammalian target of rapamycin are active in TN breast cancer with loss of PTEN tumor suppressor; antiangiogenic therapies enhance antitumor activity of chemotherapeutic agents in hypervascular TN breast cancer; and irinotecan, trabectedin, ixabepilone, and ABI-007 are active in TN breast cancer. A number of clinical trials are ongoing to clarify the antitumor activity of these challenging treatment strategies. Further biological characterization of TN breast cancer is needed to develop more specific treatment strategies against TN breast cancer.
内在亚型研究表明，乳腺癌可分为具有生物学和临床意义的亚组。大多数被归类为内在亚型之一（即基底样亚型）的乳腺肿瘤具有雌激素受体阴性、孕激素受体阴性和人表皮生长因子受体2阴性的表型，即所谓的三阴性（TN）表型；然而，TN乳腺癌并非基底样亚型的同义词。TN乳腺癌占所有乳腺癌的10%-20%，在生物学上比其他亚组的乳腺癌更具侵袭性。内分泌治疗和抗HER2治疗等针对性疗法不适用于TN乳腺癌。为了开发针对TN乳腺癌的新策略，了解驱动TN乳腺癌侵袭性行为的特定途径至关重要。临床前和临床研究表明，DNA损伤剂和聚ADP核糖聚合酶抑制剂对存在BRCA1功能障碍的TN乳腺癌有效；抗表皮生长因子受体（EGFR）抗体和EGFR酪氨酸激酶抑制剂对EGFR基因扩增的TN乳腺癌有效；达沙替尼对Src酪氨酸激酶激活的TN乳腺癌有效；雷帕霉素哺乳动物靶点抑制剂对PTEN肿瘤抑制因子缺失的TN乳腺癌有效；抗血管生成疗法可增强高血管TN乳腺癌中化疗药物的抗肿瘤活性；伊立替康、曲贝替定、伊沙匹隆和ABI-007对TN乳腺癌有效。目前正在进行多项临床试验以阐明这些具有挑战性的治疗策略的抗肿瘤活性。需要对TN乳腺癌进行进一步的生物学特征分析，以开发针对TN乳腺癌更具特异性的治疗策略。
