The triple negative paradox: Primary tumor chemosensitivity of breast cancer subtypes
The triple negative paradox: Primary tumor chemosensitivity of breast cancer subtypes
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DOI：
10.1158/1078-0432.ccr-06-1109
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发表时间：
2007-04-15
影响因子：
11.5
通讯作者：
Perou, Charles M.
中科院分区：
文献类型：
--
作者：
Carey, Lisa A.;Dees, E. Claire;Perou, Charles M.
目的：基因表达分析确定几种乳腺癌亚型。我们研究了这些乳腺癌亚型中新辅助化疗反应与结果的关系。实验设计：我们使用免疫组织化学谱[人表皮生长因子受体2阳性（HER 2+）/激素受体阴性为HER 2 +/雌激素受体阴性（ER-），激素受体和HER 2-为基底样，激素受体-鲁米诺阳性]来对用基于蒽环类药物的新辅助（多柔比星加环磷酰胺，AC）化疗治疗的乳腺癌患者的前瞻性维持数据集进行亚型分析。我们分析了每个亚型的临床和病理反应，新辅助化疗，并检查反应的关系，以远距离无病生存和总survival.Results：在107例患者测试，34（32%）是基底样，11（10%）是HER 2 +/ER-，62（58%）是管腔。新辅助AC后，75%接受后续化疗，如果激素受体阳性，则全部接受内分泌治疗。化疗方案和预处理阶段没有因亚型而异。对AC的临床反应在HER 2 +/ER-（70%）和基底样（85%）中高于管腔亚型（47%; P < 0.0001）。病理完全缓解发生在36%的HER 2 +/ER-、27%的基底细胞样和7%的管腔亚型中（P = 0.01）。尽管有初始化疗敏感性，但基底细胞样和HER 2 +/ER-亚型患者的无远处转移生存率（P = 0.04）和总生存率（P = 0.02）均低于管腔亚型患者。无论何种亚型，17例病理完全缓解患者中仅2例复发。基底细胞样和HER 2 +/ ER-亚型的预后差是由于残留病灶的复发率较高（P = 0.003）。结论：基底细胞样和HER 2 +/ER-亚型对蒽环类新辅助化疗的敏感性高于管腔型乳腺癌。对化疗有病理完全反应的患者预后良好，无论其亚型如何。基底细胞样和HER 2 +/ER-乳腺癌预后较差的原因可能是未达到病理完全缓解的患者复发的可能性较高。
Purpose: Gene expression analysis identifies several breast cancer subtypes. We examined the relationship of neoadjuvant chemotherapy response to outcome among these breast cancer subtypes.Experimental Design: We used immunohistochemical profiles [human epidermal growth factor receptor 2-positive (HER2+)/hormone receptor - negative for HER2+/estrogen receptor negative (ER-), hormone receptor and HER2- for basal-like, hormone receptor - positive for luminal] to subtype a prospectively maintained data set of patients with breast cancer treated with neoadjuvant a nthracycline-based (doxorubicin plus cyclophosphamide, AC) chemotherapy. We analyzed each subtype for clinical and pathologic response to neoadjuvant chemotherapy and examined the relationship of response to distant disease-free survival and overall survival.Results: Of the 107 patients tested, 34 (32%) were basal-like, 11 (10%) were HER2+/ER-, and 62 (58%) were luminal. After neoadjuvant AC, 75% received subsequent chemotherapy and all received endocrine therapy if hormone receptor - positive. The chemotherapy regimen and pretreatment stage did not differ by subtype. Clinical response to AC was higher among the HER2+/ER- (70%) and basal-like (85%) than the luminal subtypes (47%; P < 0.0001). Pathologic complete response occurred in 36% of HER2+/ER-, 27% of basal-like, and 7% of luminal subtypes (P = 0.01). Despite initial chemosensitivity, patients with the basal-like and HER2+/ER- subtypes had worse distant disease-free survival (P = 0.04) and overall survival (P = 0.02) than those with the luminal subtypes. Regardless of subtype, only 2 of 17 patients with pathologic complete response relapsed. The worse outcome among basal-like and HER+/ ER- subtypes was due to higher relapse among those with residual disease (P = 0.003).Conclusions: Basal-like and HER2+/ER- subtypes are more sensitive to anthracycline-based neoadjuvant chemotherapy than luminal breast cancers. Patients that had pathologic complete response to chemotherapy had a good prognosis regardless of subtype. The poorer prognosis of basal-like and HER2+/ER- breast cancers could be explained by a higher likelihood of relapse in those patients in whom pathologic complete response was not achieved.