1] Department of Pathology, Singapore General Hospital, Singapore, Singapore [2] Department of Clinical Research, Singapore General Hospital, Singapore, Singapore [3] Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore [4] Department of Anatomical and Cellular Pathology, Chinese University of Hong Kong, Hong Kong, China.
Department of Clinical Research, Singapore General Hospital, Singapore, Singapore.
Mod Pathol. 2014 Mar;27(3):352-60. doi: 10.1038/modpathol.2013.145. Epub 2013 Aug 9.
Treatment of triple-negative invasive breast cancers, defined by the absence of estrogen and progesterone receptors and c-erbB2 expression, remains challenging. Androgen receptor, a member of the nuclear receptor superfamily that is involved in signaling pathways regulating cell proliferation, has been implicated in breast tumorigenesis. We immunohistochemically examined the expression of androgen receptor, basal markers (CK14, 34βE12) and EGFR in 699 triple-negative invasive breast cancers in tissue microarrays using the streptavidin-biotin method, and correlated the findings with clinical outcome. Positive androgen receptor expression was defined as staining of 1% or more of tumor cell nuclei. Survival outcomes were estimated with the Kaplan-Meier method and compared between groups with log-rank statistics. Cox proportional hazards models were used to determine the effect of androgen receptor on survival outcomes. Immunohistochemical positivity was observed in 38% of tumors, with the proportion of stained tumor cells ranging from 1 to 95% (mean 29%, median 10%). Androgen receptor expression was inversely associated with histologic grade and mitotic score. CK14, 34βE12 and EGFR confirmed 85% of cases to be basal-like, without significant association of basal-like phenotype with androgen receptor expression. Disease-free survival was significantly better in androgen receptor-positive triple-negative breast cancer, with a trend for improved overall survival. Decreased recurrence likelihood in both triple-negative and basal-like tumors (hazard ratio, 0.704; 95% confidence intervals, 0.498-0.994; P=0.0464; and hazard ratio, 0.675; 95% confidence intervals, 0.468-0.974; P=0.0355, respectively) was noted within 5 years of diagnosis but not thereafter. Our study suggests that loss of androgen receptor in triple-negative breast cancers augurs a worse prognosis, including those with basal-like features. More work in elucidating its relationship with mechanisms of progression, as well as trials of targeted treatment for androgen receptor-expressing triple-negative tumors, needs to be performed.
三阴性浸润性乳腺癌（定义为缺乏雌激素和孕激素受体以及 c-erbB2 表达）的治疗仍然具有挑战性。雄激素受体是核受体超家族的成员，参与调节细胞增殖的信号通路，与乳腺癌的发生有关。我们使用链霉亲和素-生物素法在组织微阵列中检查了 699 例三阴性浸润性乳腺癌中雄激素受体、基底标志物（CK14、34βE12）和 EGFR 的表达，并将这些发现与临床结果相关联。阳性雄激素受体表达定义为 1%或更多肿瘤细胞核染色。使用 Kaplan-Meier 方法估计生存结果，并通过对数秩检验比较组间差异。Cox 比例风险模型用于确定雄激素受体对生存结果的影响。免疫组织化学阳性率为 38%，染色肿瘤细胞的比例为 1%至 95%（平均 29%，中位数 10%）。雄激素受体表达与组织学分级和有丝分裂评分呈负相关。CK14、34βE12 和 EGFR 证实 85%的病例为基底样，基底样表型与雄激素受体表达无显著相关性。雄激素受体阳性的三阴性乳腺癌无病生存率显著提高，总生存率有改善趋势。在诊断后 5 年内，三阴性和基底样肿瘤的复发可能性均降低（风险比，0.704；95%置信区间，0.498-0.994；P=0.0464；风险比，0.675；95%置信区间，0.468-0.974；P=0.0355），但此后无差异。我们的研究表明，三阴性乳腺癌中雄激素受体的丢失预示着预后更差，包括具有基底样特征的患者。需要进一步研究其与进展机制的关系，并对雄激素受体表达的三阴性肿瘤进行靶向治疗。
