Savci-Heijink C Dilara, Halfwerk Hans, Hooijer Gerrit K J, Horlings Hugo M, Wesseling Jelle, van de Vijver Marc J
Department of Pathology, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands,
Breast Cancer Res Treat. 2015 Apr;150(3):547-57. doi: 10.1007/s10549-015-3352-0. Epub 2015 Mar 29.
Among breast cancer patients who develop distant metastases, there is marked variability in the clinical course, including metastasis pattern. Here, we present a retrospective study of breast cancer patients who all developed distant metastases focusing on the association between breast cancer subtype and clinical course, including organ-specific metastasis. Tissue microarrays (TMAs) were assembled and stained for ER, PR, HER2, EGFR, CK5/6, CK14, E-Cadherin, TP53 and Ki67 for 263 breast cancer patients with metastatic disease. Tumours were classified into ER+/HER2-/Ki67high, ER+/HER2-/Ki67low, ER+/HER2+, ER-/HER2+ and ER-/HER2- groups. Relevant data related to metastasis pattern, metastasis timeline, systemic treatment and survival were retrieved. Associations between site-specific relapse and patient/tumour characteristics were assessed with multivariate models using logistic regression. Median time for development of distant metastasis was 30 months (range 0-15.3 years); 75.8 % of the distance metastases developed in the first 5 years after treatment of the primary tumour. Patients with ER-/HER2- tumours had a median overall survival of 27 months; those with HER2+ tumours of 52 months; those with ER+/HER2-/Ki67high of 76 months and those with ER+/HER2-/Ki67low of 79 months. Bone was the most common site for distant metastasis (70.6 %) followed by liver (54.5 %) and lung (31.4 %), respectively. Visceral metastasis was found in 76.8 % of the patients. Patients with ER-/HER2- tumours developed visceral metastases in 81 % and bone metastases in 55.2 %; those with HER2+ tumours developed visceral metastases in 77.4 % and bone metastases in 69.8 %; those with ER+/HER2-/Ki67high developed visceral metastases in 75.7 % and bone metastases in 87.8 % and those with ER+/HER2-/Ki67low developed visceral metastases in 76.9 % and bone metastases in 73.1 %. In metastatic breast cancer patients, tumour subtypes are associated with survival and pattern of distant metastases. These associations are of help in choices for surveillance and therapy in individual patients.
在发生远处转移的乳腺癌患者中,临床病程存在显著差异,包括转移模式。在此,我们对所有发生远处转移的乳腺癌患者进行了一项回顾性研究,重点关注乳腺癌亚型与临床病程之间的关联,包括器官特异性转移。我们为263例转移性疾病的乳腺癌患者组装了组织微阵列(TMA),并对其进行雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体2(HER2)、表皮生长因子受体(EGFR)、细胞角蛋白5/6(CK5/6)、细胞角蛋白14(CK14)、E-钙黏蛋白、抑癌基因p53(TP53)和细胞增殖抗原(Ki67)染色。肿瘤被分为ER+/HER2-/Ki67高表达组、ER+/HER2-/Ki67低表达组、ER+/HER2+组、ER-/HER2+组和ER-/HER2-组。检索了与转移模式、转移时间线、全身治疗和生存相关的相关数据。使用逻辑回归的多变量模型评估特定部位复发与患者/肿瘤特征之间的关联。远处转移发生的中位时间为30个月(范围0 - 15.3年);75.8%的远处转移发生在原发性肿瘤治疗后的前5年。ER-/HER2-肿瘤患者的中位总生存期为27个月;HER2+肿瘤患者为52个月;ER+/HER2-/Ki67高表达患者为76个月,ER+/HER2-/Ki67低表达患者为79个月。骨是最常见的远处转移部位(70.6%),其次是肝(54.5%)和肺(31.4%)。76.8%的患者发生了内脏转移。ER-/HER2-肿瘤患者发生内脏转移的比例为81%,骨转移的比例为55.2%;HER2+肿瘤患者发生内脏转移的比例为77.4%,骨转移的比例为69.8%;ER+/HER2-/Ki67高表达患者发生内脏转移的比例为75.7%,骨转移的比例为87.8%;ER+/HER2-/Ki67低表达患者发生内脏转移的比例为76.9%,骨转移的比例为73.1%。在转移性乳腺癌患者中,肿瘤亚型与生存及远处转移模式相关。这些关联有助于为个体患者选择监测和治疗方案。