【作者】 赵圆圆；

【导师】 邱新光；

【作者基本信息】 郑州大学 ， 外科学（普通外科学）（专业学位）， 2023， 硕士

【摘要】 研究背景国家癌症中心最新数据表明我国恶性肿瘤的发病率呈现持续增长态势,其中甲状腺癌发病率位居城市女性恶性肿瘤第4位,而乳腺癌发病率位居我国女性恶性肿瘤首位。两种肿瘤均好发于女性患者,这对女性身心健康造成极大威胁。近年来有关多原发癌的报道日渐增多,临床上甲状腺癌合并乳腺癌患者也越来越常见。大量流行病学证据表明,甲状腺癌和乳腺癌之间存在某种潜在生物学联系,但尚缺乏一致意见。目前多数研究主要探讨乳腺癌后再患甲状腺癌的临床病理特征及危险因素,而关于甲状腺癌后再患乳腺癌这一特殊群体的研究相对较少。目的本研究旨在探讨甲状腺癌与乳腺癌之间可能存在的联系以及甲状腺癌后再患乳腺癌的影响因素,以期提高对甲状腺癌合并乳腺癌的认识,为其诊治提供临床参考。方法选择郑州大学第一附属医院2016年12月1日至2022年3月31日期间收治的甲状腺癌合并乳腺癌的双原发恶性肿瘤患者124例（双原发癌组）,其中同时期（两癌确诊间隔时间≤6个月）确诊甲状腺癌与乳腺癌的患者71例（同时组）;不同时期（两癌确诊间隔时间>6个月）确诊的患者53例,其中先确诊甲状腺癌后确诊乳腺癌的患者15例（甲乳组）;先确诊乳腺癌后确诊甲状腺癌的患者38例（乳甲组）。按照1:4的比例随机选择同期收治的仅患甲状腺癌而无乳房病变患者（甲状腺癌组）60例与甲乳组对照;仅患乳腺癌无甲状腺病变患者（乳腺癌组）152例与乳甲组对照。收集患者一般资料、术前血清学指标、甲状腺癌与乳腺癌病理特征、免疫学指标等。应用t检验、方差分析、秩和检验及卡方检验对各组一般特征及病理特征等数据进行统计学分析,探讨甲状腺癌与乳腺癌之间可能存在的联系,应用Logistic回归分析探究甲状腺癌患者再患乳腺癌的风险因素。结果1.一般特征:124例双原发癌患者中,甲乳组15例（12.1%）,乳甲组38例（30.6%）,同时组71例（57.3%）。各组甲状腺癌病理类型均以乳头状癌为主,而乳腺癌病理类型均以浸润性癌（非特殊类型）为主。乳甲组两癌确诊间隔时间小于甲乳组,乳甲组已绝经人数占比高于乳腺癌组,以上差异均有统计学意义（P<0.05）。2.临床病理特征:（1）甲乳组与甲状腺癌组相比:肿瘤最大径更小、微小癌占比更高、不易紧邻/侵犯被膜、游离四碘甲状腺原氨酸（Free Tetraiodothyronine,FT4）水平更低、甲状腺球蛋白（Thyroglobulin,TG）与甲状腺球蛋白抗体（Thyroglobulin Antibody,TGAb）水平更高,差异均有统计学意义（P<0.05）。两组碘131治疗情况无统计学差异（P>0.05）。（2）甲乳组、乳甲组、同时组三组相比:甲乳组TG与TGAb水平高于同时组与乳甲组,乳甲组TG水平高于同时组,同时组较甲乳组与乳甲组更易紧邻/侵犯被膜,乳甲组颈侧区淋巴结转移患者占比多于同时组,差异均具有统计学意义（P<0.05）。但乳甲组与同时组中央区淋巴结转移情况无统计学差异（P>0.05）。三组碘131治疗情况无统计学差异（P>0.05）。3.BRAF^V600E突变:甲乳组与甲状腺癌组,甲乳组、乳甲组与同时组,双原发癌组与甲状腺癌组BRAF^V600E突变情况均无统计学差异（P>0.05）。4.乳腺癌分子分型:乳甲组与乳腺癌组分子分型无统计学差异（P>0.05）。双原发癌组与乳腺癌组相比,Luminal A型多但三阴型少,差异有统计学意义（P<0.05）。5.甲状腺癌患者再患乳腺癌风险因素分析:低FT4水平（OR=0.031,95%CI（0.001～0.721）,P=0.030）是甲状腺癌患者再患乳腺癌的危险因素;高TG水平（OR=1.076,95%CI（1.003～1.155）,P=0.042）是甲状腺癌患者再患乳腺癌的危险因素。结论1.甲状腺癌患者低FT4、高TG水平可能会增加再患乳腺癌的风险。同时甲状腺癌后再患乳腺癌者甲状腺肿瘤最大径小,更倾向于微小癌且不易紧邻/侵犯被膜。甲状腺癌术后碘131治疗可能不会增加患者再患乳腺癌的风险。2.乳腺癌患者再患甲状腺癌风险可能高于甲状腺癌患者再患乳腺癌的风险。乳腺癌后再患甲状腺癌患者甲状腺肿瘤进展较快,较同时期患两癌患者易出现颈部淋巴结跳跃性转移。3.BRAF^V600E可能不是共患甲状腺癌与乳腺癌的影响因素。4.Luminal A型乳腺癌患者较三阴型乳腺癌患者再患甲状腺癌的可能性大。更多还原

【Abstract】 Research backgroundThe latest data from the National Cancer Center show that the incidence of malignant tumors in China has shown a continuous growth trend,among which the incidence of thyroid cancer ranks fourth among urban female malignant tumors,and the incidence of breast cancer ranks first among female malignant tumors in China.Both tumors tend to occur in female patients,which poses a great threat to women’s physical and mental health.In recent years,reports of multiple primary carcinomas have been increasing,and thyroid cancer combined with breast cancer has become more and more common clinically.A large body of epidemiological evidence confirms a potential biological link between thyroid cancer and breast cancer,but there is a lack of consensus.At present,most studies focus on the risk factors and related links of thyroid cancer after breast cancer,while relatively few studies have been conducted on the special group of thyroid cancer after breast cancer.ObjectiveThis study aimed to explore the possible association between thyroid cancer and breast cancer and the influencing factors of subsequent breast cancer after thyroid cancer,in order to increase the understanding of thyroid cancer combined with breast cancer and provide clinical reference for its diagnosis and treatment.MethodsA total of 124 patients with thyroid cancer and breast cancer（double primary cancer group）was admitted in The First Affiliated Hospital of Zhengzhou University from December 1,2016 to March 31,2022 was selected,including 71 patients（simultaneous group）diagnosed with thyroid cancer and breast cancer during the same period（the interval between the diagnosis of two cancers was≤6 months）.Among patients diagnosed with two cancer at different times（the interval between the diagnosis of two cancers was>6 months）,15 patients were diagnosed with thyroid cancer first and then breast cancer（methyl breast group）;38 patients were diagnosed with breast cancer first and then thyroid cancer（breast methyl group）.According to the ratio of 1:4,60 patients with thyroid cancer without breast lesions（thyroid cancer group）admitted at the same period were randomly selected to control with the methyl breast group,and 152 patients with breast cancer without thyroid lesions（breast cancer group）were compared with the breast methyl group.General information of patients,preoperative serological indicators,pathological characteristics of thyroid cancer and breast cancer and immunological indicators were collected.The t-test,analysis of variance,rank sum test and chi-square test were used to statistically analyze the general characteristics and pathological features of each group to explore the possible relationship between thyroid cancer and breast cancer,and use logistic regression analysis to explore the risk factors of patients with thyroid cancer have breast cancer.Results1.General characteristics:Among the 124 patients with double primary cancer,the methyl breast group had 15 patients（12.1%）,the breast methyl group had 38patients（30.6%）and the simultaneous group had 71 cases（57.3%）;The pathological types of thyroid cancer in all groups were mainly papillary carcinoma,and the pathological types of breast cancer were mainly invasive ductal carcinoma.The interval between the diagnosis of two cancers in the methyl breast group was longer than that in the breast methyl group,and the proportion of menopausal people in the breast methyl group was higher than that in the breast cancer group,and the difference was statistically significant（P<0.05）.2.Clinicopathological features:（1）The methyl breast group was compared with the thyroid cancer group:the maximum tumor diameter is smaller,the proportion of microcarcinomas is higher,it is not easy to adjacent/invade the membrane,the level of free tetraiodothyronine（FT4）is lower,and the level of thyroglobulin（TG）and thyroglobulin antibody（TGAb）is higher.The differences were all statistically significant（P<0.05）.There was no significant difference in the treatment of iodine131 between the two groups（P>0.05）.（2）The methyl breast group,breast methyl group and simultaneous group was compared with each other:the TG and TGAb levels of the methyl breast group were higher than those in the simultaneous group and the breast methyl group,the TG level in the breast methyl group was higher than that in the simultaneous group,and the simultaneous group were more likely to be adjacent/invaded the membrane than the methyl breast group and breast methyl group,and the proportion of patients with lymph node metastasis in the cervical area of the breast methyl group was more than that in the simultaneous group,and the difference was statistically significant（P<0.05）.However,there was no significant difference in lymph node metastasis in the central region of the breast methyl group and the simultaneous group（P>0.05）.There was no significant difference in the treatment of iodine 131 between the three groups（P>0.05）.3.BRAF^V600Emutations:There were no significant differences in BRAF^V600Emutations between the simultaneous group,the methyl breast group and the breast methyl group,the methyl breast group and the thyroid cancer group,the double primary cancer group and the thyroid cancer group（P>0.05）.4.Molecular typing of breast cancer:There was no significant difference in molecular typing between the breast cancer group and the breast methyl group（P>0.05）.Compared with breast cancer group,the double primary cancer group had more Luminal A type but less triple-negative type,and the difference was statistically significant（P<0.05）.5.Analysis of risk factors for getting breast cancer after thyroid cancer:low FT4level（OR=0.031,95%CI（0.001～0.721）,P=0.030）is a risk factor for comorbid breast cancer in thyroid cancer patients,and high TG level（OR=1.076,95%CI（1.003～1.155）,P=0.042）is a risk factor for comorbid breast cancer in thyroid cancer patients.Conclusions1.Low FT4 and high TG levels in patients with thyroid cancer may increase the risk of getting breast cancer.At the same time,patients with breast cancer after thyroid cancer have a small thyroid tumor and are more inclined to microcarcinoma and are not easy to adjacent/invade the membrane.Treatment with iodine-131 after thyroid cancer surgery may not increase the risk of getting breast cancer.2.The risk of developing thyroid cancer after breast cancer may be higher than the risk of developing breast cancer after thyroid cancer for patients.Patients with thyroid cancer after breast cancer have faster progression of thyroid tumors,and are more likely to have cervical lymph node jumping metastasis than patients with two cancers in the same period.3.BRAF^V600E may be not a contributing factor in comorbid thyroid and breast cancer.4.Luminal type A breast cancer patients are more likely to develop thyroid cancer than triple-negative type breast cancer patients.更多还原