乳腺癌骨转移和内分泌治疗的临床研究
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摘要
乳腺癌发病率很高，2000年全球癌症统计显示，乳腺癌的发病率仅次于肺癌，居第二位，而乳腺癌是最容易发生骨转移的肿瘤，骨转移伴随的各种并发症又严重影响患者的生活质量。因此，本研究旨在通过我科多年积累的临床资料的回顾性分析，总结乳腺癌骨转移的临床规律、对比研究单独内分泌治疗和单独化疗对无内脏转移的骨转移的疗效，并系统分析晚期乳腺癌内分泌治疗的相关因素，以期对复发转移乳腺癌内科合理治疗提供循证医学的证据。
第一部分研究，回顾性分析345例乳腺癌患者骨转移好发部位、病灶特点、发生时间、激素受体分布情况及预后等规律。结果发现，乳腺癌骨转移好发部位依次是腰椎、胸椎、骨盆、肋骨和股骨；几乎全部是溶骨性病灶；中位发生骨转移时间是术后33个月；88.7％患者就诊时有相应症状；骨转移患者中激素受体阳性比例较高；首发骨转移的预后介于软组织和内脏之间；延缓骨转移与内脏转移的间隔时间有利于生存期的改善。
第二部分研究，对138例无内脏转移的骨转移患者，单独内分泌治疗177例次与单独化疗112例次的治疗结果进行了随访研究。其一线治疗有效率分别为35.4％和31.7％(P=0.687)，二线治疗为23.9％和24.2％(P=0.973)，全部线次总有效率为27.1％和25.0％(P=0.690)，两者起效时间都在2个月左右；而临床获益率一线治疗分别为43.9％和36.6％(P=0.437)，但二线治疗为47.8％和24.2％(P=0.033)，差异有显著意义，全部治疗为47.5％和27.7％(P=0.001)有非常显著意义；临床控制患者的中位TTF分别为5月和2月(P＜0.001)，中位TTP为5月和2.5月(P＜0.001)，均有非常显著意义。内分泌治疗和化疗都是乳癌骨转移的有效手段，其中内分泌治疗优于化疗。
第三部分研究的对象，从骨转移扩展到单纯接受内分泌治疗的，有ER、PgR、HER-2检测结果的132例，189例次的各种复发转移晚期乳癌患者。集中分析了内分泌治疗的相关因素，发现初治和复治患者的有效率分别33.3％和14.1％(P=0.003)；抗雌激素类、孕激素类和芳香化酶抑制剂初治患者的有效率分别为0、25％和39.5％(P=0.038)；绝经前患者卵巢切除后，或药物去势同时加用芳香化酶
硕去学吞论丈
中文摘要
抑制剂，与绝经后患者疗效相当;软组织、骨和内脏的有效率分别为21.5%、20.2%
和9.3%(尸=0.020)，无内脏转移的乳腺癌骨转移和软组织转移是内分泌治疗的适
应症;ER阳性和阴性患者的有效率分别为22.6%、3.3%(尸二0.015)，ER是预测内
分泌药物疗效肯定有价值的指标，PgR和HER一2对治疗的预测价值并不肯定。
By analyzing clinical data accumulated over years, we conducted this retrospective study to achieve the following goals: 1) to ascertain the clinical regularity of bone metastasis in patients with breast cancer; 2) to compare the efficacy of endocrine therapy and chemotherapy in non-visceral metastasis patients; 3) to analyze the relevant factors associated with endocrine therapy in metastatic breast cancer (MBC), and ultimately provide reasonable evidence-based medical verification for treatment of MBC.
In first part of this study, we found the most common sites of bone metastases were lumber thoracic vertebra . pelvis . rib and femur, almost all of the bone metastases tended to be osteolytic. The median time of bone metastasis was 33 months after the surgical procedure, which ranged from 0 to 15 years. There was a higher hormone receptor-positive proportion in patients with bone metastasis, and the prognosis of those patients was better than visceral metastasis ones.
In second part, we compared the efficacy of two systemic therapies in bone metastasis patients without viscera involved. The efficacy of first-line endocrine and chemotherapy for breast cancer patients with bone metastasis were 35.4% and 31.7%, respectively. (P=0.687), whereas the second-line efficacy were 23.9% and 24.2% (=0.973), the overall response rate were 27.1% and 25.0%(P=0.690). The CBR of first-line endocrine and chemotherapy in these patients were 43.9% and 36.6%(P=0.437), whereas the CBR of second-line treatment were 47.8% and 24.2% (P=0.033), and the CBR of all treatments were 47.5% and 27.7% (P=0.001), respectively, these differences were all significant. The mean TTF of the endocrine and chemotherapy arm were 5 months and 2 months (P<0.001),whereas the mean TTP were 5 months and 2.5 months (P<.001) in clinical control patients, the differences were all significant. We concluded that endocrine therapy alone is superior to chemotherapy alone in non-visceral metastasis patients.
In the third part of the study, Analysis of the patient who identified by ER, PgR and HER-2 , demonstrated that the response rate of first-line and heavily treated endocrine therapy were 33.3% and 14.1% (P=0.003) ; the response rate for anti-estrogens, progesterone and aromatase inhibitors in first-line therapy were O. 25% and 39.5% (.P=0.038); the response rate of soft tissue metastasis, bone metastasis and viscera metastasis were 21.5%, 20.2% and 9.3% (P=0.020) ,which show that comparing with viscera metastatic patients, those with soft tissue and bone metastasis alone have a relative good clinical outcome , therefore, endocrine therapy is suitable for this kind of patients; The response rate of endocrine therapy in estrogen receptor -positive and negative group were 22.6% and 3.3% (P=0.015), so ER is an predictive factor of endocrine therapy, whereas the predictive role of PgR status and HER-2 is uncertain.
第一部分研究，回顾性分析345例乳腺癌患者骨转移好发部位、病灶特点、发生时间、激素受体分布情况及预后等规律。结果发现，乳腺癌骨转移好发部位依次是腰椎、胸椎、骨盆、肋骨和股骨；几乎全部是溶骨性病灶；中位发生骨转移时间是术后33个月；88.7％患者就诊时有相应症状；骨转移患者中激素受体阳性比例较高；首发骨转移的预后介于软组织和内脏之间；延缓骨转移与内脏转移的间隔时间有利于生存期的改善。
第二部分研究，对138例无内脏转移的骨转移患者，单独内分泌治疗177例次与单独化疗112例次的治疗结果进行了随访研究。其一线治疗有效率分别为35.4％和31.7％(P=0.687)，二线治疗为23.9％和24.2％(P=0.973)，全部线次总有效率为27.1％和25.0％(P=0.690)，两者起效时间都在2个月左右；而临床获益率一线治疗分别为43.9％和36.6％(P=0.437)，但二线治疗为47.8％和24.2％(P=0.033)，差异有显著意义，全部治疗为47.5％和27.7％(P=0.001)有非常显著意义；临床控制患者的中位TTF分别为5月和2月(P＜0.001)，中位TTP为5月和2.5月(P＜0.001)，均有非常显著意义。内分泌治疗和化疗都是乳癌骨转移的有效手段，其中内分泌治疗优于化疗。
第三部分研究的对象，从骨转移扩展到单纯接受内分泌治疗的，有ER、PgR、HER-2检测结果的132例，189例次的各种复发转移晚期乳癌患者。集中分析了内分泌治疗的相关因素，发现初治和复治患者的有效率分别33.3％和14.1％(P=0.003)；抗雌激素类、孕激素类和芳香化酶抑制剂初治患者的有效率分别为0、25％和39.5％(P=0.038)；绝经前患者卵巢切除后，或药物去势同时加用芳香化酶
硕去学吞论丈
中文摘要
抑制剂，与绝经后患者疗效相当;软组织、骨和内脏的有效率分别为21.5%、20.2%
和9.3%(尸=0.020)，无内脏转移的乳腺癌骨转移和软组织转移是内分泌治疗的适
应症;ER阳性和阴性患者的有效率分别为22.6%、3.3%(尸二0.015)，ER是预测内
分泌药物疗效肯定有价值的指标，PgR和HER一2对治疗的预测价值并不肯定。
By analyzing clinical data accumulated over years, we conducted this retrospective study to achieve the following goals: 1) to ascertain the clinical regularity of bone metastasis in patients with breast cancer; 2) to compare the efficacy of endocrine therapy and chemotherapy in non-visceral metastasis patients; 3) to analyze the relevant factors associated with endocrine therapy in metastatic breast cancer (MBC), and ultimately provide reasonable evidence-based medical verification for treatment of MBC.
In first part of this study, we found the most common sites of bone metastases were lumber thoracic vertebra . pelvis . rib and femur, almost all of the bone metastases tended to be osteolytic. The median time of bone metastasis was 33 months after the surgical procedure, which ranged from 0 to 15 years. There was a higher hormone receptor-positive proportion in patients with bone metastasis, and the prognosis of those patients was better than visceral metastasis ones.
In second part, we compared the efficacy of two systemic therapies in bone metastasis patients without viscera involved. The efficacy of first-line endocrine and chemotherapy for breast cancer patients with bone metastasis were 35.4% and 31.7%, respectively. (P=0.687), whereas the second-line efficacy were 23.9% and 24.2% (=0.973), the overall response rate were 27.1% and 25.0%(P=0.690). The CBR of first-line endocrine and chemotherapy in these patients were 43.9% and 36.6%(P=0.437), whereas the CBR of second-line treatment were 47.8% and 24.2% (P=0.033), and the CBR of all treatments were 47.5% and 27.7% (P=0.001), respectively, these differences were all significant. The mean TTF of the endocrine and chemotherapy arm were 5 months and 2 months (P<0.001),whereas the mean TTP were 5 months and 2.5 months (P<.001) in clinical control patients, the differences were all significant. We concluded that endocrine therapy alone is superior to chemotherapy alone in non-visceral metastasis patients.
In the third part of the study, Analysis of the patient who identified by ER, PgR and HER-2 , demonstrated that the response rate of first-line and heavily treated endocrine therapy were 33.3% and 14.1% (P=0.003) ; the response rate for anti-estrogens, progesterone and aromatase inhibitors in first-line therapy were O. 25% and 39.5% (.P=0.038); the response rate of soft tissue metastasis, bone metastasis and viscera metastasis were 21.5%, 20.2% and 9.3% (P=0.020) ,which show that comparing with viscera metastatic patients, those with soft tissue and bone metastasis alone have a relative good clinical outcome , therefore, endocrine therapy is suitable for this kind of patients; The response rate of endocrine therapy in estrogen receptor -positive and negative group were 22.6% and 3.3% (P=0.015), so ER is an predictive factor of endocrine therapy, whereas the predictive role of PgR status and HER-2 is uncertain.
引文
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2．曹旭晨，刘翠芝，于金芳，等．145例乳腺癌骨转移临床病理分析．齐鲁肿瘤杂志，1999,6(2)：120-122．
3．陈国林，王凤军，庞达，等．乳癌术后骨转移的探讨．实用肿瘤学杂志，1999,13(4)281-282．
4．宋三泰，汤仲明，陈美云，等．乳癌组织取样、保存及测定方法对ER测定量的影响及其意义．中华肿瘤杂志，1985：7(5)：351-352．
5．张克勤．乳腺癌与雌激素受体关系．金显宅主编．乳腺癌的研究(第一集)．天津科学技术出版社，1987：139．
6. Solomayer EF, Diel IJ, Meyberg GC, et al. Metastatic breast cancer: clinical course, prognosis and therapy related to the first site of metastasis. Breast Cancer Res Treat, 2000, 59(3):271-278.
7. Mundy GR. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer, 2002, 2(8):584-593.
8．汤仲明，宋三泰，苏燕燕，等．乳癌他莫西芬(Tamoxifen)治疗反应和雌激素受体的依赖关系．中国临床药理学杂志，1988,4(1)：1-5．
9．宋三泰，汤仲明，苏燕燕，等．氨格鲁米特治疗不同雌激素受体状态的复发转移乳腺癌．新药与临床，1988，7(2)：65-68．
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