Hans Journal of Surgery
Vol.07 No.03(2018), Article ID:24988,5 pages
10.12677/HJS.2018.73014

Therapeutic Experience of Breast Cancer with Thyroid Cancer: 1 Case Report

Mingwen Zhu, Zongming Zhang, Fangcai Lin*, Limin Liu, Hai Deng, Chong Zhang, Hongwei Yu, Zhuo Liu, Baijiang Wan, Haiyan Yang, Mengmeng Song, Yue Zhao

Department of General Surgery, Beijing Electric Power Hospital, State Grid Corporation of China, Capital Medical University, Beijing

Received: Apr. 25th, 2018; accepted: May 15th, 2018; published: May 22nd, 2018

ABSTRACT

Breast cancer is one of the most common malignant tumors in women, with the incidence of about 7%~10% of all kinds of malignant tumors in the whole body, which seriously affects the physical and mental health of women, and even threatens her life. Thyroid cancer is the most common malignancy of thyroid, which accounts for about 1% of malignant tumors in the whole body, and occurs more frequently in females than males, with the incidence of male to female for 1:2 to 1:4. In recent years, although the incidence of breast cancer and thyroid cancer has been increasing, it is rare that breast cancer is combined with thyroid cancer. Based on our experience of the accurate diagnosis and treatment of one patient with breast cancer combined with thyroid cancer, the pathophysiological mechanism and therapeutic principle are discussed, so as to improve its curative effect, and to avoid missed diagnosis and omitted treatment.

Keywords:Breast Cancer, Thyroid Cancer, Double Primary Cancer, Surgery, Endocrine Therapy

乳腺癌合并甲状腺癌1例诊治体会

朱明文,张宗明,林方才*,刘立民,邓海,张翀,于宏伟,刘卓,万柏江,杨海燕, 宋蒙蒙,赵月

首都医科大学北京电力医院普外科,北京

收稿日期:2018年4月25日;录用日期:2018年5月15日;发布日期:2018年5月22日

摘 要

乳腺癌是女性最常见的恶性肿瘤之一,发病率约占全身各种恶性肿瘤的7%~10%,严重影响女性的身心健康,甚至威胁生命。甲状腺癌是最常见的甲状腺恶性肿瘤,约占全身恶性肿瘤的1%,女性发病较多,男女发病比例为1:2~1:4。近年来,尽管乳腺癌与甲状腺癌的发病率有逐渐上升趋势,但乳腺癌同时合并甲状腺癌者却很少见。本文结合我们对一例乳腺癌合并甲状腺癌患者的精准诊治体会,深入探讨其发生机制及诊治原则,以期提高其诊治效果,避免漏诊漏治。

关键词 :乳腺癌,甲状腺癌,双原发癌,手术,内分泌治疗

Copyright © 2018 by authors and Hans Publishers Inc.

This work is licensed under the Creative Commons Attribution International License (CC BY).

http://creativecommons.org/licenses/by/4.0/

1. 前言

多原发癌是指同一器官或不同器官同时或先后发生两种或两种以上的原发性恶性肿瘤 [1] 。多原发癌目前仍沿用Warren S和Gates O早在1932年报道的诊断标准 [2] :1) 每个肿瘤应有肯定的病理学恶性肿瘤的证据;2) 各个肿瘤必须发生于不同部位或器官;3) 各有独特的病理形态特征;4) 应排除转移和复发癌的可能。按照其出现的时间先后可分为同时性(≤6个月)和异时性(>6个月)多原发癌。本文结合我们对一例同时性多原发癌(乳腺癌合并甲状腺癌)患者的精准诊治体会,深入探讨乳腺癌合并甲状腺癌的发生机制和诊治策略,以期提高其诊治效果。

2. 病例资料

2.1. 一般情况

患者,女性,46岁,主因“体检发现左乳肿物7天”于2017年12月19日入北京电力医院。该病例报道已经获得患者的知情同意。

查体:双侧乳腺大小对称,无外观改变,无乳头内陷,左乳外下象限距乳头约3 cm可触及一大小约3 × 4 cm肿物,质硬、表面光滑、活动度差、无触痛。左侧腋窝可触及到一直径约0.5 cm淋巴结,质硬、表面光滑、可推动。右乳未触及肿物,右侧腋窝及双侧锁骨上未触及肿大淋巴结。甲状腺无肿大,未触及明确结节,颈部未触及肿大淋巴结。辅助检查:甲状腺功能及血常规、生化、肿瘤标记物均正常。乳腺钼靶检查:左乳外下象限可见一毛刺样肿块影,大小约2.9 × 2.1 cm,密度不均匀,边缘不光滑,左腋下可见淋巴结,见图1(A),图1(B)。乳腺超声检查:左乳外下象限4B可见一大小约2.88 × 1.8 cm肿物,轮廓不规整,周边呈蟹足样改变,内为低回声,分布欠均匀,边缘可见强回声,后方回声衰减,其内可见血流信号;左侧腋窝未见异常回声,见图1(C)。甲状腺超声检查:甲状腺左叶可见0.7 × 0.4 cm结节样回声,边界清楚,内可见点状强回声,未见血流信号,见图2(A)。甲状腺CT检查:甲状腺左叶结节伴钙化,见图2(B),图2(C)。胸部CT、腹部超声及CT、骨扫描均未发现转移灶。术前诊断:左侧乳腺肿物,恶性可能性大;左侧甲状腺肿物,恶性可能性大。

A-B 乳腺钼靶:左乳外下象限可见一毛刺样肿块影(红色箭头),大小约2.9 × 2.1 cm,密度不均匀,边缘不光滑;左腋下可见淋巴结(黑色箭头)。C 乳腺超声:左乳外下象限4B可见一大小约2.88 × 1.8 cm肿物(红色箭头),轮廓不规整,周边呈蟹足样改变,内为低回声,分布欠均匀,边缘可见强回声,后方回声衰减。D-E 乳腺病理:乳腺浸润性髓样癌,HE染色,D (×100),E (×200)。

Figure 1. Imaging and pathological examination of the breast

图1. 乳腺影像和病理检查

A 甲状腺超声:甲状腺左叶可见0.7 × 0.4 cm结节样回声,边界清楚,内可见多发点状强回声(红色箭头)。B-C 甲状腺CT:甲状腺左叶结节伴钙化(红色箭头)。D 甲状腺癌大体标本(红色箭头)。E-F 甲状腺病理:甲状腺乳头状癌,HE染色,E (×100),F (×200)。

Figure 2. Imaging and pathological examination of the thyroid

图2. 甲状腺影像和病理检查

2.2. 手术治疗

患者于2017年12月22日在全麻下行左乳区段切除术,术中将肿物及周边1~2 cm组织一起锐性切除,见肿物大小约3 × 4 cm,边界不清,质硬,切开呈灰白色,术中冰冻病理示:乳腺浸润性癌。予以行左侧乳腺癌改良根治术,术后石蜡病理示:乳腺髓样癌,见图1(D),图1(E),大小2.5 × 2.2 × 1.8 cm,ER(-)、PR(-)、HER-2(-)、KI67 (70%),淋巴结转移1/21,病理分期T2N1M0。1周后(2017年12月28日)在全麻下行甲状腺左叶及峡部切除术,术中见甲状腺左叶中下部有一肿物,质硬、边界清楚,剖面呈灰白色(见图2(D)),术中冰冻病理示:甲状腺微小乳头状癌,直径0.7 cm,见图2(E),图2(F),术后石蜡病理与术中冰冻病理结果一致,病理分期T1N0M0。

2.3. 术后治疗

甲状腺癌内分泌治疗:甲状腺术后第2天给予左甲状腺素钠片(优甲乐) 50 μg,口服,每日1次。初期TSH抑制目标值为0.1~0.5 μU/mL,随访期为0.5~2.0 μU/mL。

乳腺癌化疗:甲状腺术后1周给予表柔比星联合环磷酰胺序贯多西他赛(EC-T)方案:表柔比星90 mg/m2,环磷酰胺600 mg/m2,静脉滴注,第1天,每3周重复,共4个周期;序贯多西他赛75 mg/m2,静脉滴注,第1天,每3周重复,共4个周期。

2.4. 随访

迄今随访3个月,患者乳腺、甲状腺无肿瘤复发,肝、肺、脑、骨无转移。

3. 讨论

乳腺癌除合并甲状腺癌外,尚可发生于对侧乳腺、子宫内膜、卵巢、结肠、肺、皮肤、骨髓系统等,但以合并甲状腺癌最为多见 [3] 。An JH 等 [4] 回顾性研究了6833例乳腺癌和4243例甲状腺癌患者,随访40年,发现1.2% (81例)乳腺癌患者再发甲状腺癌(中位期6.2年),1.3% (55例)甲状腺癌患者再发乳腺癌(中位期5年),并且在5年内诊断出第二原发癌,其临床特征与第一原发癌表现出更多相一致的地方。Zhang L 等 [5] 随访了18,732例乳腺癌及12,877例甲状腺癌患者,发现0.49% (91例)乳腺癌患者在随访过程中发生甲状腺癌(中位期4.09年),且具有较高水平的甲状腺球蛋白抗体及甲状腺过氧化物酶;而0.91% (117例)甲状腺癌患者随访过程中发生乳腺癌(中位期5.82年),且多数为Ki-67高表达、雌激素受体(estrogen receptor, ER)和孕激素受体(progesterone receptor, PR)阳性。本例患者仅有一项符合,即Ki-67高表达(70%),而甲状腺球蛋白抗体及甲状腺过氧化物酶均正常,ER、PR均阴性。

关于乳腺与甲状腺之间发病关系的研究最早开始于18世纪 [6] ,Nielsen SM 等 [7] 研究发现,与普通人相比,乳腺癌患者再发甲状腺癌的风险增加(OR = 1.55, 95% CI = 1.44~1.67),同样甲状腺癌患者再发乳腺癌的风险亦增加(OR = 1.18, 95% CI = 1.09~1.26),并且乳腺癌患者再发甲状腺癌的风险比甲状腺癌患者再发乳腺癌的风险要高。目前的研究表明甲状腺和乳腺同属于内分泌器官,存在相互作用的激素受体通路:1) 雌激素受体在甲状腺癌中的表达高于正常甲状腺组织 [8] [9] 。Prinzi N等 [10] 研究发现β-雌二醇可以明显刺激甲状腺癌细胞的增生,呈现时间和浓度依赖性,并且该作用被雌激素拮抗剂三苯氧胺所抑制,表明β-雌二醇可以促进甲状腺肿瘤的发生和发展。2) 甲状腺激素,特别是三碘甲状腺原氨酸(triiodothyronine, T3),通过与雌激素信号系统的相互作用可以模仿或增强雌激素对乳腺癌增殖的影响,在乳腺癌的发生和进展中起着重要作用 [11] 。3) 钠碘同向转运蛋白(sodium iodide symporter, NIS)是一种调控甲状腺滤泡细胞碘吸收的跨膜糖蛋白,可以介导碘的转运,提高细胞内的碘含量。正常情况下NIS表达于甲状腺组织与哺乳期的乳腺组织,在非哺乳期的乳腺组织中没有表达 [12] 。有研究发现NIS在乳腺癌中的表达水平显著高于正常乳腺组织,尤其是ER阳性的乳腺癌组织,NIS的阳性表达率可达89% [13] [14] ,NIS在甲状腺癌中也是高表达,提示钠碘转运体也可能参与乳腺癌与甲状腺癌的共同通路。

目前还没有乳腺癌并发甲状腺癌相关病理类型的研究,胡早秀等 [15] 报道21例乳腺癌并发甲状腺癌病例中,19例为乳腺癌非特殊型浸润性导管癌,l例为黏液癌,1例为浸润性小叶癌,再发甲状腺癌均为甲状腺乳头状癌。本例患者乳腺癌为髓样癌,甲状腺癌为乳头状腺癌。但由于病例较少,有关乳腺癌合并甲状腺癌病理类型及其相关性还需进一步研究证实。

综上所述,乳腺癌与甲状腺癌存在一定的相关性,因此对于乳腺癌患者应常规检查甲状腺功能及甲状腺超声,并在随诊过程中定期复查,以便早发现、早治疗。甲状腺超声是甲状腺疾病的首选影像学检查,能够发现一些临床上触不到、直径 < 1 cm的结节。该患者即通过甲状腺超声发现的直径0.7 cm结节。同时甲状腺癌患者亦应定期检查乳腺超声和/或钼靶,以免漏诊漏治。

文章引用

朱明文,张宗明,林方才,刘立民,邓海,张翀,于宏伟,刘卓,万柏江,杨海燕,宋蒙蒙,赵 月. 乳腺癌合并甲状腺癌1例诊治体会
Therapeutic Experience of Breast Cancer with Thyroid Cancer: 1 Case Report[J]. 外科, 2018, 07(03): 85-89. https://doi.org/10.12677/HJS.2018.73014

参考文献

  1. 1. Fante, R., Roncucci, L., Di Gregorio, C., et al. (1996) Frequency and Clinical Features of Multiple Tumors of the Large Bowel in General Population and in Patients with Hereditary Colorectal Carcinoma. Cancer, 77, 2013-2021. https://doi.org/10.1002/(SICI)1097-0142(19960515)77:10%3C2013::AID-CNCR8%3E3.0.CO;2-R

  2. 2. Warren, S. and Gates, O. (1932) Multiple Primary Malignant Tumors, a Survey of the Literature and a Statistical Study. American Journal of Cancer, 16, 1358-1363.

  3. 3. Subramanian, S., Goldstein, D.P., Parlea, L., et al. (2007) Second Primary Malignancy Risk in Thyroid Cancer Survivors: A Systematic Review and Meta-Analysis. Thyroid, 17, 1277-1288. https://doi.org/10.1089/thy.2007.0171

  4. 4. An, J.H., Hwangbo, Y., Ahn, H.Y., et al. (2015) A Possible Association between Thyroid Cancer and Breast Cancer. Thyroid, 25, 1330-1338. https://doi.org/10.1089/thy.2014.0561

  5. 5. Zhang, L., Wu, Y., Liu, F., et al. (2016) Characteristics and Sur-vival of Patients with Metachronous or Synchronous Double Primary Malignancies: Breast and Thyroid Cancer. Oncotarget, 7, 52450-52459. https://doi.org/10.18632/oncotarget.9547

  6. 6. Beatson, G. (1896) On the Treatment of Inoperable Cases of Carcinoma of the Mamma Suggestions for a New Method of Treatment, with Illustrative Cases. Lacent, 2, 104-110.

  7. 7. Nielsen, S.M., White, M.G., Hong, S., et al. (2016) The Breast-Thyroid Cancer Link: A Systematic Review and Meta Analysis. Cancer Epidemiology, Biomarkers & Prevention, 25, 231-238. https://doi.org/10.1158/1055-9965.EPI-15-0833

  8. 8. Yane, K., Kitahori, Y., Konishi, N., et al. (1994) Ex-pression of the Estrogen Receptor in Human Thyroid Neoplasms. Cancer Letters, 84, 59-66. https://doi.org/10.1016/0304-3835(94)90358-1

  9. 9. Rajoria, S., Suriano, R., Shanmugam, A., et al. (2010) Metastatic Phenotype Is Regulated by Estrogen in Thyroid Cells. Thyroid, 20, 33-41. https://doi.org/10.1089/thy.2009.0296

  10. 10. Prinzi, N., Baldini, E., Sorrenti, S., et al. (144) Prevalence of Breast Cancer in Thyroid Diseases: Results of a Cross-Sectional Study of 3,921 Patients. Breast Cancer Research and Treatment, 2014, 683-688. https://doi.org/10.1007/s10549-014-2893-y

  11. 11. Hall, L.C., Salazar, E.P., Kane, S.R., et al. (2008) Effects of Thyroid Hormones on Human Breast Cancer Cell Proliferation. The Journal of Steroid Biochemistry and Molecular Biology, 109, 57-66. https://doi.org/10.1016/j.jsbmb.2007.12.008

  12. 12. Micali, S., Bulotta, S., Puppin, C., et al. (2014) Sodium Iodide Symporter (NIS) Inextrathyroidal Malignancies: Focus on Breast and Urological Cancer. BMC Cancer, 14, 303. https://doi.org/10.1186/1471-2407-14-303

  13. 13. Ryan, J., Curran, C.E., Hennessy, E., et al. (2011) The Sodium Iodide Sym-Porter (NIS) and Potential Regulators in Normal, Benign and Malignant Human Breast Tissue. PLoS ONE, 6, e16023. https://doi.org/10.1371/journal.pone.0016023

  14. 14. Chatterjee, S., Malhotra, R., Varghese, F., et al. (2013) Quantitative Immunohistochemical Analysis Reveals Association between Sodiumiodide Symporter and Estrogen Receptor Expression in Breast Cancer. PLoS ONE, 8, e54055. https://doi.org/10.1371/journal.pone.0054055

  15. 15. 胡早秀, 赵永和, 陈亚娟. 乳腺癌再发甲状腺癌与单发甲状腺癌ER表达的研究[J]. 诊断病理学杂志, 2016, 23(2): 124-126.

NOTES

*通讯作者。

期刊菜单