年龄与三阴性乳腺癌临床病理特征及预后的关系

Association of age at diagnosis with clinicopathologic features and prognosis in patients with triple-negative breast cancer

背景与目的:年龄与乳腺癌的发病、肿瘤生物学行为及预后密切相关,是临床决策的重要参考因素。不同年龄反映了患者的不同生理状态,由于三阴性乳腺癌(TNBC)缺失激素受体属于激素非依赖性,年龄是否影响该类患者的诊疗决策和预后有待研究。本研究旨在探讨诊断年龄与TNBC患者临床病理特征、治疗策略及预后的关系。方法:从美国SEER数据库中提取2010-2016年经病理诊断为Ⅰ~Ⅲ期的TNBC患者的病例资料,根据患者乳腺癌的诊断年龄将病例划分为18~39岁、40~49岁、50~59岁、60~69岁及≥70岁5组,比较各年龄组间的临床病理特征及治疗差异,采用多因素Cox比例风险模型分析年龄与患者的乳腺癌特异生存(BCSS)的关系并计算风险比(HR)和95%置信区间(CI)。结果:30 576例TNBC纳入分析,中位年龄57岁(IQR:48~67岁),其中18~39岁3 007例(9.83%)、40~49岁6 071例(19.86%)、50~59岁8 097例(26.48%)、60~69岁7 176例(23.47%)和≥70岁6 225例(20.36%)。各年龄组患者间的诊断年份、种族、婚姻状态、肿瘤TNM分期、病理类型、组织学分级、手术治疗及是否放化疗的分布差异有统计学意义(均P<0.05)。随着诊断年龄的增加,肿瘤T分期和N分期呈现降低,组织学分级更好,治疗保乳率更高而化疗率更低。中位随访32个月(IQR:15~54个月),乳腺癌相关死亡3 482例(11.39%),各年龄段患者间的BCSS率差异有统计学意义(P<0.001)。单因素Cox比例风险模型分析结果显示,患者的诊断年龄、种族、婚姻状态、肿瘤T分期、淋巴结分期、肿瘤TNM分期、病理类型、组织学分级、手术治疗及放疗与BCSS明显有关(均P<0.05),化疗与BCSS无明显关系(P=0.284)。多因素Cox模型的校正分析结果显示,18~39岁(HR=1.00,95%CI=0.88~1.13,P=0.990)、40~49岁(HR=0.95,95%CI=0.85~1.06,P=0.330)和50~59岁(HR=1.03,95%CI=0.93~1.14,P=0.597)患者的BCSS与60~69岁患者比较差异无统计学意义,而年龄≥70岁患者的BCSS较60~69岁患者差(HR=1.56,95%CI=1.41~1.74,P<0.001)。在不同诊断年份、TNM分期、手术方式和放化疗状态的亚组人群中,年龄与BCSS的关系基本相似。结论:TNBC患者的诊断年龄与预后存在相关性,高龄(≥70岁)是患者的不良预后因素,而18~69岁患者的预后基本相似。

Background and Aims: Age is closely related to the incidence, biological behavior and prognosis of breast cancer, and is an important reference factor for clinical decision-making. Different ages reflect different physiological states of the patients. Since the absence of hormone receptors in triple-negative breast cancer(TNBC) is sex hormone-independent, whether age affects the treatment decisions and prognosis of these patients remains to be studied. This study was conducted to investigate the relationship between age at diagnosis and clinicopathologic features, treatment strategies, and prognosis of TNBC patients.Methods: The data of TNBC patients diagnosed as stage Ⅰ to Ⅲ during 2010 to 2016 were extracted from the SEER database. Patients were divided into five groups defined as 18-39 years, 40-49 years,50-59 years, 60-69 years, and ≥70 years group, according to the age at diagnosis. Comparisons of clinicopathologic features and treatments were performed among different age-groups. Multivariate Cox proportional risk model was used to analyze the relationship between age at diagnosis and breast cancer specific survival(BCSS), and the hazard ratio(HR) with corresponding 95% confidence interval(CI)was calculated.Results: A total of 30 576 TNBC patients with a median age of 57 years(IQR: 48-67 years) met the criteria were enrolled in the final analysis. Among them, 3 007 cases(9.83%) aged from 18 to 39 years old, 6 071 cases(19.86%) aged from 40 to 49 years old, 8 097 cases(26.48%) aged from 50 to 59 years old, 7 176 cases(23.47%) aged from 60 to 69 years old and 6 225 cases(20.36%) aged ≥70 years old.The distributions of diagnosis year, race, marital status, TNM stage, pathological type, histological grade,surgical treatment and radiotherapy or chemotherapy had significant difference among groups(all P<0.05). With the increase of age at diagnosis, the T stage and N stage were declined, histological grade was improved, and the rates of mastectomy and chemotherapy were reduced. The median follow-up was 32 months(IQR: 15-54 months), and breast cancer-related death occurred in 3 482 cases(11.39%). The BCSS rate was statistically different among different age groups(P<0.001). The univariate Cox proportional analysis showed that the age at diagnosis, race, marital status, T stage, lymph node stage,TNM stage, pathological type, histological grade, surgical treatment and radiotherapy were significantly associated with BCSS(all P<0.05), but no significant connection was observed between the chemotherapy and BCSS(P=0.284). The multivariate Cox analysis showed that patients with the age of 18-39 years(HR=1.00, 95% CI=0.88-1.13, P=0.990), 40-49 years(HR=0.95, 95% CI=0.85-1.06, P=0.330), and 50-59 years(HR=1.03, 95% CI=0.93-1.14, P=0.597) had a similar BCSS with patients aged 60-69 years, while patients aged ≥70 years had a worse BCSS than those aged 60-69 years(HR=1.56,95% CI=1.41-1.74, P<0.001). The relationship between age at diagnosis and BCSS was similar in subgroup patients with different years of diagnosis, TNM stages, surgical treatment, radiation status, and chemotherapy status.Conclusion: Age at diagnosis is significantly associated with the prognosis of TNBC, elder age(≥70 years old) is an independent poor prognostic factor, and the survival is similar among patients aged from 18 to 69 years old.