• 中国科技论文统计源期刊
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  • 中国高校优秀期刊
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Volume 44 Issue 9
Sep.  2019
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The clinical analysis of 210 cases of triple-negative breast cancer

  • Corresponding author: DONG Hui-ming, ahbbdong@163.com
  • Received Date: 2017-05-30
    Accepted Date: 2018-11-06
  • ObjectiveTo investigate the clinicopathologic characteristics, prognosis and its risk factors of triple-negative breast cancer(TNBC).MethodsThe clinical data of 210 patients with TNBC(observation group) and 70 non-TNBC patients(control group) from September 2010 to September 2015 were retrospectively analyzed.ResultsThe lymph node metastasis rate was related to the tumor size, and the larger the tumor size, the higher the lymph node metastasis rate was(P < 0.01).Compared with the coincidence rate of pathological diagnosis of ultrasound or mammography, the coincidence rate of combined diagnosis was the highest(97.46%)(P < 0.01), and the coincidence rates of ultrasound and mammography were 84.76% and 70.0%, respectively(P < 0.01).The pathological histological classification in observation group was higher than that in control group(P < 0.01).Prognostic analysis showed that the recurrence rate and survival rate in observation group(42.38%, 74.29%) were higher and lower than those in control group(28.57%, 85.71%) respectively(P < 0.05).The larger the tumor size, the higher the lymph node metastasis rate was(P < 0.01).The survival rate in patients with negative lymph node(86.00%) was higher than that in patients with positive lymph node(65.45%)(P < 0.01).ConclusionsCompared with the non-TNBC, the tumor size is large, the age of patient is young, the pathological histological classification is high, the relapse and metastasis are ease, and the prognosis is poor in TNBC.Ultrasonography and mammography are the effective methods in auxiliary diagnosis of TNBC, and the correct rate of combination of both methods is higher.Larger tumor size and lymph node metastasis are the risk factors of TNBC death.
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  • [1] ANDERS CK, CAREY LA.Biology, metastatic patterns, and treatment of patients with triple-negative breast cancer[J].Clin Breast Cancer, 2009, 9(Suppl 2):S73.
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    [6] JUNG HK, HAN K, LEE YJ, et al.Mammographic and sonographic features of triple-negative invasive carcinoma of no special type[J].Ultrasound Med Biol, 2015, 41(2):375. doi: 10.1016/j.ultrasmedbio.2014.09.006
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    [8] 陈圆圆, 李智贤, 魏晏平, 等.超声联合钼靶X线对三阴性乳腺癌的诊断价值[J].重庆医学, 2013, 42(30):3662. doi: 10.3969/j.issn.1671-8348.2013.30.027
    [9] 张桦, 崔志英, 严梦寒, 等.超声及钼靶在三阴性乳腺癌诊断中的价值[J].医药论坛杂志, 2016, 37(4):43.
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    [13] 杨猛, 戴殿禄, 崔国忠, 等.三阴性与非三阴性乳腺癌的临床病理分类与病理特征研究[J].现代中西医结合杂志, 2015, 24(24):2713. doi: 10.3969/j.issn.1008-8849.2015.24.037
    [14] HASHMI AA, EDHI MM, NAQVI H, et al.Clinicopathologic features of triple negative breast cancers:an experience from Pakistan[J].Diagn Pathol, 2014, 9(1):43.
    [15] QIU J, XUE X, HU C, et al.Comparison of clinicopathological features and prognosis in triple-negative and non-triple negative breast cancer[J].J Cancer, 2016, 7(2):167. doi: 10.7150/jca.10944
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    [22] 王雅杰, 王宁, 王斌, 等.三阴性乳腺癌与人表皮生长因子受体2过表达乳腺癌病人的临床病理特征和预后比较[J].中华肿瘤杂志, 2009, 31(5):346. doi: 10.3760/cma.j.issn.0253-3766.2009.05.006
    [23] LEE JH, KIM SH, SUH YJ, et al.Predictors of axillary lymph node metastases(ALNM) in a Korean population with T1-2 breast carcinoma:triple negative breast cancer has a high incidence of ALNM irrespective of the tumor size[J].Cancer Res Treat, 2010, 42(1):30. doi: 10.4143/crt.2010.42.1.30
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The clinical analysis of 210 cases of triple-negative breast cancer

    Corresponding author: DONG Hui-ming, ahbbdong@163.com
  • Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu Anhui 233004, China

Abstract: ObjectiveTo investigate the clinicopathologic characteristics, prognosis and its risk factors of triple-negative breast cancer(TNBC).MethodsThe clinical data of 210 patients with TNBC(observation group) and 70 non-TNBC patients(control group) from September 2010 to September 2015 were retrospectively analyzed.ResultsThe lymph node metastasis rate was related to the tumor size, and the larger the tumor size, the higher the lymph node metastasis rate was(P < 0.01).Compared with the coincidence rate of pathological diagnosis of ultrasound or mammography, the coincidence rate of combined diagnosis was the highest(97.46%)(P < 0.01), and the coincidence rates of ultrasound and mammography were 84.76% and 70.0%, respectively(P < 0.01).The pathological histological classification in observation group was higher than that in control group(P < 0.01).Prognostic analysis showed that the recurrence rate and survival rate in observation group(42.38%, 74.29%) were higher and lower than those in control group(28.57%, 85.71%) respectively(P < 0.05).The larger the tumor size, the higher the lymph node metastasis rate was(P < 0.01).The survival rate in patients with negative lymph node(86.00%) was higher than that in patients with positive lymph node(65.45%)(P < 0.01).ConclusionsCompared with the non-TNBC, the tumor size is large, the age of patient is young, the pathological histological classification is high, the relapse and metastasis are ease, and the prognosis is poor in TNBC.Ultrasonography and mammography are the effective methods in auxiliary diagnosis of TNBC, and the correct rate of combination of both methods is higher.Larger tumor size and lymph node metastasis are the risk factors of TNBC death.

  • 三阴性乳腺癌(triple-negative breast cancer,TNBC)占乳腺癌总数的12%~20%[1],其雌激素受体(estrogen receptor, ER)、孕激素受体(progestogen receptor, PR)及人类表皮生长因子受体2(human epidermal growth factor receptor-2, HER-2)表达缺失,是乳腺癌中最具侵袭力的亚型。研究者已普遍认同“三阴”只是TNBC复杂异质性的一个共性,其本身亦存在不同亚型,并且不同亚型在临床特征方面明显不同,但对于其分类暂无统一标准[2-3]。TNBC从乳腺癌的传统治疗方法中获益有限,预后很差。本研究对210例TNBC病人的病例资料进行回顾性分析,为TNBC的进一步研究提供参考。

1.   资料与方法
  • 收集2010年9月至2015年9月我院收治的乳腺癌病人病例资料,TNBC病人共210例,列为观察组,并选取同期收治经病理证实为非TNBC病人70例作为对照组。对2组病人的年龄、乳腺癌家族史、月经状态、超声及钼靶检查结果、病理结果等临床资料进行对比分析。

  • 参照病人术后的免疫组化检查报告,将ER和PR按以下标准进行判定:其中0为阴性,+~3+则为阳性。HER-2结果0~+为阴性,3+则为阳性;2+者则进一步参照荧光原位杂交(FISH)检查结果,HER-2无扩增为阴性,有扩增为阳性。当且仅当ER、PR及HER-2同时符合阴性者判定为TNBC。

  • 对于210例TNBC病人的超声及钼靶检查结果均采用美国放射学会推荐的BI-RADS分级系统评分。其中,Ⅰ~Ⅲ级倾向于良性病变,判断为与诊断不相符;Ⅳ~Ⅴ级倾向于恶性病变,判断为与诊断相符。超声及钼靶中任一结果为Ⅳ~Ⅴ级即为联合诊断相符。

  • 对所有入组病人采用电话、门诊复查或住院复查的方式进行随访,随访至2017年4月5日(随访过程中死亡病人截止日期为死亡日期),随访时间为19~79个月,中位随访时间为47个月。随访内容包括生存状态,复发和转移,复查结果等。

  • 采用χ2检验和秩和检验。

2.   结果
  • 观察组肿瘤长径大于对照组,发病年龄低于对照组,差异有统计学意义(P<0.05)。2组在淋巴结状态、发病部位、乳腺癌家族史上和月经状态方面差异均无统计学意义(P>0.05)(见表 1)。

    项目 观察组(n=210) 对照组(n=70) χ2 P
    肿瘤长径/cm
        <2 22(10.48) 12(14.14) 6.33 <0.05
        2~5 111(52.86) 43(61.43)
        >5 77(36.67) 15(21.43)
    淋巴结状态
        阴性
        阳性
    100(47.62)
    110(52.38)
    38(54.29)
    32(45.71)
    0.93 >0.05
    肿瘤部位
        外上象限 153(72.86) 52(74.29) 3.98 >0.05
        外下象限 18(8.57) 9(12.86)
        内上象限 18(8.57) 2(2.86)
        内下象限 5(2.38) 2(2.86)
        乳晕区 16(7.62) 5(7.14)
    年龄/岁
        <50
        ≥50
    136(64.76)
    74(35.24)
    36(51.43)
    34(48.57)
    3.94 <0.05
    家族史
        无
        有
    201(95.71)
    9(4.29)
    68(97.14)
    2(2.86)
    0.28 >0.05
    月经状态
        未绝经
        已绝经
    135(64.29)
    75(35.71)
    38(54.29)
    32(45.71)
    2.22 >0.05
  • 观察组210例TNBC病人中,淋巴结阳性组肿瘤长径大于淋巴结阴性组(P<0.01)(见表 2)。

    分组 n T1 T2 T3 平均秩和
    淋巴结阳性 110 9 51 50 116.02
    淋巴结阴性 100 14 60 26 93.93
    uc 2.94
    P <0.01
  • 观察组超声检查Ⅳ~Ⅴ级共178例,诊断相符率84.76%(178/210)。钼靶检查Ⅳ~Ⅴ级共147例,诊断相符率70.00%(147/210)。联合检查(超声+钼靶)中任一结果为Ⅳ~Ⅴ级共199例,诊断相符率94.76%(199/210)。三种检查相符率差异有统计学意义(χ2=46.57, P<0.01), 联合检查相符率最高(P<0.01),超声次之(P<0.01),钼靶最低(P<0.01)。

  • 观察组中病理类型分布与对照组差异无明显统计学意义(P>0.05),病理组织学分级高于对照组(P<0.01)(见表 3)。

    项目 观察组(n=210) 对照组(n=70) χ2 P
    病理类型
        浸润性导管癌 186(88.57) 61(87.14) 1.83 >0.05
        浸润性小叶癌 7(3.33) 2(2.86)
        髓样癌 3(1.43) 0(0.00)
        其他 14(6.67) 7(10.00)
    病理组织学分级
        Ⅰ级 34(16.19) 20(28.57) 3.52* <0.01
        Ⅱ级 69(32.86) 31(44.29)
        Ⅲ级 107(50.95) 19(27.14)
        平均秩和 149.61 113.17
    *示uc
  • 随访结果表明,观察组复发率42.38%,高于对照组的28.57%(P<0.05),观察组生存率74.29%,低于对照组的85.71%(P<0.05)(见表 4)。

    项目 观察组(n=210) 对照组(n=70) χ2 P
    复发部位
        腋窝 25(11.90) 10(14.29) 2.24 <0.05
        对侧乳腺 12(5.71) 5(7.14)
        其他部位 52(24.76) 5(7.14)
    生存状况
        存活 156(74.29) 60(85.71) 3.89 <0.05
  • TNBC肿瘤长径越大,生存率越低(P<0.01)。淋巴结阴性者存活率86.00%,高于淋巴结阳性者存活率的65.45%(P<0.01)。低年龄(<50岁)和高年龄(≥50岁)病人存活率分别为76.52%和73.08%,差异无统计学意义(P>0.05)(见表 5)。

    项目 存活 死亡 χ2 P
    肿瘤长径/cm
        <2 20(86.96) 3(13.04) 12.01 <0.01
        2~5 92(82.88) 19(17.12)
        >5 46(60.53) 30(39.47)
    淋巴结状态
        阴性
        阳性
    86(86.00)
    72(65.45)
    14(14.00)
    38(34.54)
    11.87 <0.01
    年龄/岁
        <50
        ≥50
    101(76.52)
    57(73.08)
    31(23.48)
    21(26.92)
    0.31 >0.05
3.   讨论
  • TNBC是乳腺癌中最具侵袭力的一种亚型,由于ER、PR、HER-2的表达缺失,对内分泌和靶向治疗不敏感,TNBC从乳腺癌的传统治疗方法中获益有限,因此,TNBC一直是近年来乳腺癌领域的研究热点和难点。虽然TNBC恶性程度高于非TNBC,但其影像学特点却更倾向于良性病变,缺少其他乳腺癌常有的恶性征象,因此影像学检查容易漏诊和误诊。相关报道[4-7]显示,TNBC影像学上多表现为边缘较清晰、形状较规则、回声较均匀、少见边缘毛刺和微钙化。陈圆圆等[8]报道,超声和钼靶对TNBC的诊断相符率分别为89.36%和72.34%,两者联合相符率提高93.61%。张桦等[9]报道,超声和钼靶对TNBC的诊断相符率分别为88.2%和72.1%,两者联合相符率提高到94.1%。本研究中,超声和钼靶对TNBC的诊断相符率分别为84.76%和70.00%,两者联合相符率提高到94.76%,这与上述研究结果基本一致。

    本研究中,与对照组相比,观察组肿瘤长径更大、发病年龄更小,差异均有统计学意义。2组淋巴结状态、乳腺癌家族史、发病部位无明显差异。这与朱明华等[10-11]等研究结果相一致。观察组≤2 cm、2~5 cm、>5 cm的比例分别为10.48%(22/210)、52.86%(111/210)和36.67%(77/210),对照组分别为14.14%(12/70)、61.43%(43/70)和21.43%(15/70),差异有统计学意义,说明TNBC肿瘤长径更大。这与HAMM等[12]研究结果一致。杨猛等[13]对55例TNBC的研究表明,病理类型的比例分别为浸润性导管癌80.0%、髓样癌12.7%、导管内癌5.5%,非TNBC病理类型的比例分别为浸润性导管癌81.2%、小叶癌6.9%、导管内癌7.2%,且TNBC和非TNBC病理类型差异有统计学意义。本研究中,TNBC病理类型的比例分别为浸润性导管癌88.57%、髓样癌1.43%、小叶癌3.33%,非TNBC病理类型的比例分别为浸润性导管癌87.14%、小叶癌2.86%,TNBC和非TNBC病理类型差异无统计学意义。这与上述研究结果不符,但与HASHMI等[14]研究相符,HASHMI等研究指出,浸润性导管癌在TNBC和非TNBC中均占大多数,两组之间无明显差异。本研究中,TNBC病理分级的比例分别为Ⅰ级16.19%,Ⅱ级32.86%,Ⅲ级50.95%,非TNBC病理分级的比例分别为Ⅰ级28.57%,Ⅱ级44.29%,Ⅲ级27.14%。TNBC组病理组织学分级高于非TNBC,差异有统计学意义。这与QIU等[15-18]的研究结果一致,TNBC病理组织学分级为Ⅲ级的比率更高。

    ONITILO等[19-20]研究表明,TNBC的局部和骨转移比例最高。另有研究表明,TNBC与非TNBC的局部复发率比较无明显差异,但TNBC远处转移率明显高于非TNBC[21]。这与本研究结果相符,本研究中,TNBC各部位转移的比例分别为腋窝11.90%,对侧乳腺5.71%,其他部位24.76%。非TNBC各部位转移的比例分别为腋窝14.29%, 对侧乳腺7.14%, 其他部位7.14%。其他部位转移率明显高于非TNBC。

    王雅杰等[22]研究表明,肿瘤长径≤2 cm病人淋巴结转移的阳性比例为50%,而肿瘤长径>5 cm病人淋巴结转移的阳性比例高达81.8%,说明肿瘤长径与淋巴结转移呈正相关关系。本研究中,TNBC淋巴结转移的阳性比例分别为肿瘤长径≤2 cm 39.13%, 2~5 cm 49.95%, >5 cm 65.79%,淋巴结转移率随肿瘤长径增大而升高,与上述研究结果相符。但也有研究表明,TNBC肿瘤大小与淋巴结转移无关[23]。本研究中,TNBC无病生存率和总生存率分别为57.62%和74.29%,非TNBC无病生存率和总生存率分别为71.43%和85.71%,非TNBC生存状态明显优于TNBC,这与STEWARD等[24]的研究结果相符。另外,SCHMIDT等[25]研究表明,T1期病人预后优于T2~T4期病人,N0期病人预后优于N1~N3期病人。本研究中,肿瘤长径≤2 cm、2~5 cm、>5 cm病人总生存率分别为86.96%,82.88%,60.53%,淋巴结阴性和淋巴结阳性病人总生存率分别为86.00%和65.45%,与上述研究结果相符。DENT等[26]也有相似研究,T1期病人较T2~T4期病人的中位生存时间明显更长,分别为4.5年和2.7年,但两者的10年病死率并无明显差异(42%:41%)。

    综上所述,与非TNBC相比,TNBC发病年龄更低、肿瘤长径更大、病理组织学分级更高,更易发生远处复发和转移,预后更差。TNBC的肿瘤大小与淋巴结转移有关,肿瘤长径越大,发生淋巴结转移的风险越大。对于TNBC的辅助检查,超声优于钼靶,且二者联合检查的诊断相符率更高。TNBC的预后不良与肿瘤长径和淋巴结阳性相关,而与病人年龄无关。

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