【作者】 方芳；

【导师】 顾林；

【作者基本信息】 天津医科大学 ， 肿瘤学， 2022， 硕士

【摘要】 目的:通过分析近年青年乳腺癌患者的临床病理特征及预后,总结其发病规律及预后相关危险因素,为青年乳腺癌的预防及个体化治疗提供参考。方法:对天津医科大学肿瘤医院乳腺外科自2007年1月1日起至2012年1月1日止收治过的女性乳腺癌病例资料进行收集,并对资料进行回顾性分析。按照纳入标准和排除标准共筛选出3783例女性乳腺癌患者。按照临床病人的发病年龄将上述病例分为两组,发病年龄≦35周岁的患者为青年组患者(共计205例),发病年龄>35周岁的患者为中老年组患者(共计3578例)。分析比较两组病例的一般临床资料、妇科相关因素、既往病史及家族史、临床病理资料的差异。一般的临床数据资料主要包括患者的年龄、接受学校教育的时间/程度、BMI指数等;妇科相关的影响因素主要包括患者月经初潮年龄、怀孕或生育妊娠史、自患者月经初潮年龄至第一次足月妊娠年龄之间的时间间隔、患者末次妊娠的年龄、发病时距患者的上次生育子女的时间、分娩史、哺乳史、哺乳时间等;既往有无乳腺疾病及家族成员是否有良性乳腺疾病史或癌症病史等信息;相关的临床影像检查与病理资料则包括乳房肿瘤部位的大小、淋巴结是否有异常肿大情况、肿瘤组织学和分期、雌激素受体(ER)、孕激素受体(PR)和人表皮细胞生长因子受体2(HER-2)表达情况、分子分型等。资料用SPSS23.0统计软件进行统计检验或处理,计量资料处理采用t检验,计数资料检验采用X2检验,以α=0.05为检验的标准,P值<0.05说明检验结果有统计学意义。预后综合评价研究的单因素分析采用Log-rank法,利用Kaplan-Meier法进行生存风险曲线的回归分析,多因素回归的回归分析还可同时采用COX比例风险曲线作为回归的分析模型,P因子<0.05时有重大统计学意义。结果:1.临床资料1.1共收集青年乳腺癌患者205例,占总例数的5.4%(205/3783),平均年龄为31.14岁,31-35岁年龄段分布比例最高。中老年乳腺癌患者3578例,占总例数的94.6%(3578/3783),平均年龄为52.77岁,46-50岁年龄段分布比例最高。1.2两组患者均以接受中学教育为主,中老年组比例略高于青年组,74.3%vs 70.2%,差异有统计学意义。青年组病例中BMI指数≤23kg/m2的比例高于中老年组,58.1%vs 30.1%,差异有统计学意义(P<0.01)。1.3妇科因素中青年组患者在月经初潮年龄≤13岁、无怀孕史、分娩次数0次或1次、第一次足月妊娠年龄在20-24岁等所占比例均高于中老年组,分别为43.9%vs 26.0%、27.4%vs 3.0%、75.6%vs62.1%、46.8%vs 30.0%,差异有统计学意义(P<0.01)。月经初潮年龄与第一次足月妊娠年龄间隔及哺乳史两组之间无统计学差异(P>0.05)。1.4两组患者中有良性乳腺疾病病史者分别为青年组57例,中老年组1058例,所占比例相当,27.8%vs 29.7%,差异无统计学意义(P>0.05)。青年组有癌症家族史者比例低于中老年组,22.4%vs31.1%,差异有统计学意义(P<0.05)。1.5两组患者肿瘤直径均以大于2cm较为常见,分别为青年组97例,中老年组1885例,所占分别为62.6%,52.7%。差异有统计学意义(P<0.05)。青年组淋巴结转移阴性者比例低于中老年组,54.2%vs 62.0%,差异有统计学意义(P<0.05)。两组患者肿瘤分级均以Ⅱ期为主,所占比例明显高于其他两期,且两组之间比较差异有统计学意义(P<0.01)。1.6青年组ER阳性患者所占比例低于中老年组,53.6%vs55.1%,差异有统计学意义(P<0.05),青年组PR阳性率高于中老年组,59.0%vs52.9%,但差异无统计学意义(P>0.05),青年组在HER-2阳性表达的比率上高于中老年组,37.6%vs28.3%,两者的差异有统计学意义(P<0.01)。两组患者分子分型均以Luminal B型较为常见,且青年组发生频率低于中老年组,42.8%vs43.8,差异有统计学意义(P<0.05)。2.预后分析结果:2.1年龄对无病生存期和总生存期是独立影响因素,具体表现为40岁以下病人总生存期7年以上的比例较41-60岁病人总生存期7年以上的比例明显下降(P<0.05);40岁以下病人无病生存期6年以上的比例较41-60岁病人无病生存期6年以上的比例明显下降(P<0.05)。2.2辅助化疗在青年乳腺癌患者中疗效较差,乳腺癌患者总生存期4年以上的比例青年组(≦35周岁)较中老年组(>35周岁)明显下降(P<0.05)。2.3青年乳腺癌患者单因素分析结果显示:肿瘤>2CM、淋巴结转移对无病生存期和总生存期均是不良因素(P<0.05),HER-2+对总生存期是不良因素(P<0.05),ER、PR 阳性对总生存期是良性因素(P<0.05),分子分型结果显示乳腺癌患者总生存期6年以上所占百分比Luminal A型组>Luminal B型组>HER-2+组>三阴型组。2.4青年乳腺癌患者多因素分析结果显示肿瘤大小、淋巴结转移、HER-2+对总生存期均为不良因素(P<0.05)。结论:本研究显示1.青年乳腺癌患者具有月经初潮年龄早,分娩次数少,初次生育年龄和末次生育年龄早,BMI指数偏低等特征;2.青年女性乳腺癌在病理学特征上表现为肿瘤>2CM、淋巴结转移、HER-2(+)、三阴型患者比例均较高;3.单因素与多因素分析结果均表明肿瘤大小>2CM、淋巴结转移阳性、HER-2+为青年乳腺癌患者预后不良因素,对病人的总生存期或无病生存期产生不利影响。更多还原

【Abstract】 OBJECTIVE:To analyze the clinicopathological characteristics and prognosis of young breast cancer patients,and to summarize the incidence regularity and prognosis-related risk factors,so as to provide reference for the prevention and individualized treatment of young breast cancer.Methods:The data of female breast cancer cases admitted to the Breast Surgery Department of Tianjin Medical University Cancer Hospital from January 1st,2007 to January 1st,2012 were retrospectively collected and analyzed.A total of 3783 female breast cancer patients were screened according to the inclusion and exclusion criteria.The cases were divided into two groups according to age,205 cases in the young group(age≤35 years old)and 3578 cases in the middle-aged and elderly group(>35 years old).The general clinical data,gynecological-related factors,past medical history and family history,and clinicopathological data of the two groups were analyzed and compared.General clinical data include age,education level,BMI index;gynecological-related factors include age at menarche,pregnancy history,age at first full-term pregnancy,time interval between age at menarche and age at first full-term pregnancy,age at last pregnancy,Time since last childbirth,childbirth history,breastfeeding history,breastfeeding time;past medical history and family history including benign breast disease,family history of cancer;clinicopathological data including tumor size,lymph node metastasis,tumor stage,estrogen receptor(ER),progesterone receptor(PR)and human epidermal growth factor receptor 2(HER-2)expression,molecular typing,etc.The data of the two groups were processed by SPSS23.0 statistical software,the measurement data was by t test,the count data by X2 test,with α=0.05 as the test standard,P<0.05 was statistically significant.Univariate analysis of prognosis was performed by Log-rank method,Kaplan-Meier method was used for survival curve analysis,and multivariate analysis was performed by COX proportional hazards regression model.P<0.05 was considered statistically significant.RESULT:1.Clinical data1.1 A total of 205 young breast cancer patients were collected,accounting for 5.4%(205/3783)of the total number of cases,with an average age of 31.14 years,and the highest proportion in the age group of 31-35.There were 3578 cases of middle-aged and elderly breast cancer patients,accounting for 94.6%(3578/3783)of the total cases.1.2 The patients in both groups mainly received secondary education,and the proportion of middle-aged and elderly group was higher than that of young group,74.3%vs 70.2%,and the difference was not statistically significant.The proportion of BMI index ≤23kg/m2 in the young group was higher than that in the middle-aged and elderly group,58.1%vs 30.1%,and the difference was statistically significant(P<0.01).1.3 Gynecological factors The proportion of patients in the young and middle-aged group at the age of menarche≤13 years old,no history of pregnancy,0 or 1 delivery times,and the age of 20-24 years old for the first full-term pregnancy were higher than those in the middle-aged and old group.The ratios were 43.9%vs 26.0%,27.4%vs 3.0%,75.6%vs 62.1%,46.8%vs 30.0%,and the differences were statistically significant(P<0.01).There was no significant difference between the two groups in the age of menarche,the age of first full-term pregnancy,and the history of breastfeeding(P>0.05).1.4 There were 57 patients in the young group and 1058 in the middle-aged and elderly group with a history of benign breast disease,accounting for the same proportion,27.8%vs 29.7%,and the difference was not statistically significant(P>0.05).The proportion of those with family history of cancer in the young group was lower than that in the middle-aged and elderly group,22.4%vs 31.1%,and the difference was statistically significant(P<0.05).1.5 Tumor diameters larger than 2 cm were common in both groups,97 cases in the young group and 1885 cases in the middle-aged group,accounting for 62.6%and 52.7%,respectively.The difference was statistically significant(P<0.05).The proportion of negative lymph node metastasis in the young group was lower than that in the middle-aged and elderly group,54.2%vs 62.0%,and the difference was statistically significant(P<0.05).The tumor grades of the two groups were mainly stage II,and the proportion was significantly higher than that of the other two stages,and the difference between the two groups was statistically significant(P<0.01).1.6 The proportion of ER positive patients in the young group was lower than that in the middle-aged and elderly group,53.6%vs 55.1%,the difference was statistically significant(P<0.05).The PR positive rate in the young group was higher than that in the middle-aged and elderly group,59.0%vs 52.9%,but the difference was not statistically significant(P>0.05),the ratio of HER-2 positive expression in the young group was higher than that in the middle-aged and elderly group,37.6%vs 28.3%,the difference was statistically significant(P<0.01).Luminal B type was more common in the two groups of patients,and the frequency of the young group was lower than that of the middle-aged and elderly group,42.8%vs.43.8,and the difference was statistically significant(P<0.05).2.Prognostic analysis results:2.1 Age is an independent factor affecting disease-free survival and overall survival,specifically,the proportion of patients under 40 years old with an overall survival of more than 7 years was significantly lower than that of patients aged 41-60(P<0.05);the proportion of patients under the age of 40 with a disease-free survival of more than 6 years was significantly lower than that of patients aged 41-60(P<0.05).2.2 The efficacy of adjuvant chemotherapy in young breast cancer patients was poor,and the proportion of breast cancer patients with an overall survival of more than 4 years was significantly lower in the young group(≤35 years old)than in the middle-aged and elderly group(>35 years old)(P<0.05).2.3 Univariate analysis of young breast cancer patients showed that tumor>2CM and lymph node metastasis were adverse factors for disease-free survival and overall survival(P<0.05),and HER-2+was an adverse factor for overall survival(P<0.05).Positive ER and PR are benign factors for overall survival(P<0.05),and the molecular typing results showed that the percentage of breast cancer patients with an overall survival of more than 6 years was different,Luminal type A group>Luminal type B group>HER-2+group>triple negative type Group.2.4 The multivariate analysis of young breast cancer patients showed that tumor size,lymph node metastasis and HER-2+ were all adverse factors for overall survival(P<0.05).Conclusion:This study shows that:1.Young breast cancer patients have the characteristics of early menarche,less delivery times,early first and last childbearing age,and lower BMI index;2.The pathological characteristics of young female breast cancer are higher than 2CM,lymph node metastasis,HER-2(+)and triple negative;3.Univariate and multivariate analysis showed that tumor size>2CM,positive lymph node metastasis,and HER-2+were poor prognostic factors in young breast cancer patients,and had adverse effects on patients’ overall survival or disease-free survival.更多还原