Fredholm Hanna, Magnusson Kristina, Lindström Linda S, Tobin Nicholas P, Lindman Henrik, Bergh Jonas, Holmberg Lars, Pontén Fredrik, Frisell Jan, Fredriksson Irma
Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm, Sweden; Department of Breast- and Endocrine Surgery, Karolinska University Hospital, Stockholm, Sweden.
Uppsala University, Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala, Sweden.
Eur J Cancer. 2017 Oct;84:278-289. doi: 10.1016/j.ejca.2017.07.044. Epub 2017 Aug 29.
Compared to middle-aged women, young women with breast cancer have a higher risk of systemic disease. We studied expression of proliferation markers in relation to age and subtype and their association with long-term prognosis.
Distant disease-free survival (DDFS) was studied in 504 women aged <40 years and 383 women aged ≥40 years from a population-based cohort. Information on patient characteristics, treatment and follow-up was collected from medical records. Tissue microarrays were produced for analysis of oestrogen receptor, progesterone receptor (PR), Her2, Ki-67 and cyclins.
Young women with luminal tumours had significantly higher expression of Ki-67 and cyclins. Proliferation markers were prognostic only within this subtype. Ki-67 was a prognostic indicator only in young women with luminal PR+ tumours. The optimal cut-off for Ki-67 varied by age. High expression of cyclin E1 conferred a better DDFS in women aged <40 years with luminal PR- tumours (hazard ratio [HR] 0.47 [0.24-0.92]). Age <40 years was an independent risk factor of DDFS exclusively in women with luminal B PR+ tumours (HR 2.35 [1.22-4.50]). Young women with luminal B PR- tumours expressing low cyclin E1 had a six-fold risk of distant disease compared with luminal A (HR 6.21 [2.17-17.6]).
The higher expression of proliferation markers in young women does not have a strong impact on prognosis. Ki-67 is only prognostic in the subgroup of young women with luminal PR+ tumours. The only cyclin adding prognostic value beyond subtype is cyclin E1. Age is an independent prognostic factor only in women with luminal B PR+ tumours.
与中年女性相比，年轻乳腺癌女性发生全身疾病的风险更高。我们研究了增殖标志物的表达与年龄、亚型的关系及其与长期预后的关联。
对来自一项基于人群队列的504名年龄<40岁的女性和383名年龄≥40岁的女性进行远处无病生存期（DDFS）研究。从医疗记录中收集患者特征、治疗及随访信息。制作组织微阵列用于分析雌激素受体、孕激素受体（PR）、Her2、Ki-67和细胞周期蛋白。
管腔型肿瘤的年轻女性中，Ki-67和细胞周期蛋白的表达显著更高。增殖标志物仅在该亚型内具有预后意义。Ki-67仅是管腔型PR+肿瘤年轻女性中的预后指标。Ki-67的最佳临界值因年龄而异。细胞周期蛋白E1高表达使年龄<40岁的管腔型PR-肿瘤女性的DDFS更好（风险比[HR] 0.47 [0.24 - 0.92]）。年龄<40岁仅是管腔型B PR+肿瘤女性DDFS的独立危险因素（HR 2.35 [1.22 - 4.50]）。与管腔型A相比，细胞周期蛋白E1低表达的管腔型B PR-肿瘤年轻女性发生远处疾病的风险高6倍（HR 6.21 [2.17 - 17.6]）。
年轻女性中增殖标志物的较高表达对预后影响不大。Ki-67仅在管腔型PR+肿瘤的年轻女性亚组中具有预后意义。唯一在亚型之外增加预后价值的细胞周期蛋白是细胞周期蛋白E1。年龄仅是管腔型B PR+肿瘤女性的独立预后因素。
