乳积方预防激素受体阴性乳腺癌术后复发转移的研究
摘要
激素受体阴性乳腺癌(Hormone Receptors Negative Breast Cancer)术后患者,通过放化疗、生物治疗及靶向治疗后可以获得一定的生存期,但是大量的临床研究显示此型患者无疾病生存期(DFS)及总生存期(OS)明显低于激素受体阳性(Hormone Receptors Positive)患者。如何延长激素受体阴性乳腺癌术后患者的DFS、OS,减少复发转移发生的机率,延缓复发转移时间,改善患者生存质量成为目前乳腺癌治疗及研究的一个热点。中医药在整体观与辨证论治思想的指导下,通过减轻手术后局部症状、减轻放化疗毒副反应、调节人体内环境,从而明显改善患者生存质量,大量研究显示其能够延长患者的无病生存期(disease free survival)。
乳积方是本院自制中药方,多年的临床实践发现其在改善患者临床症状,改善生活质量,延长生存期等方面具有明显的疗效,但是目前尚缺乏循证医学的客观数据支持,所以,本研究将研究乳积方对于激素受体阴性乳腺癌术后患者在预防复发转移中的作用。
目的
本研究旨在揭示乳积方对于激素受体阴性乳腺癌综合治疗后的患者在临床症状、生存质量、生存时间、复发转移时间等方面的影响,探讨其预防乳腺癌术后复发转移的作用。方法
回顾性分析长期接受随访的42例激素受体阴性乳腺癌术后女性患者,根据随访用药治疗情况,分为治疗组和对照组,其中治疗组在综合治疗后至少服用乳积方3个月,对照组患者综合治疗后,不服用乳积方,不接受其他任何抗肿瘤治疗,仅进行定期随访。末次随访结束后,记录两组患者入组前与治疗后的临床症状评分(附表1)、肝肾功能、CEA、CA12-5、CA153、生存质量评分(乳腺癌患者生存质量测定表,FACT-B附表2)、总生存时间、复发转移时间等方面差异,并进行组间及组内比较,得出统计学差异。
结果
第一部分
1、乳积方能够改善激素受体阴性乳腺癌患者的临床症状：治疗组显效率为48%,有效率为52%,总体缓解率达到100%。临床症状的缓解率,与对照组比较,差异有统计学意义(P<0.05)；
2、乳积方能够改善化、放疗后肝功能的异常,与对照组比较差异有统计学意义(P<0.05)；
3、乳积方能够改善激素受体阴性乳腺癌患者的生活质量：
(1)PS评分：治疗前组间比较,差异无统计学意义(P>0.05)；治疗后,治疗组明显低于对照组,差异有统计学意义(P<0.05)；组内比较,治疗组治疗前后PS评分无明显波动(P>0.05),对照组有明显升高,差异有统计学意义(P<0.05)。
(2) FACT-B生命质量测定结果提示：治疗前各项指标组间比较,差异无统计学意义(P>0.05)；治疗后,治疗组生理不适、情感波动少于对照组,社会家庭功能、躯体功能情况好于对照组,差异均有统计学意义(P<0.05)。组内比较,治疗组,治疗后患者生理状况、情感状况有明显改善,差异有统计学意义(P<0.01)；社会家庭状况、功能状况有明显提高,差异有统计学意义(P<0.05)；对照组,治疗后的功能状况、附加关注较治疗前有明显减低,差异有统计学意义(P<0.05)；生理状况、社会家庭状况、情感状况治疗前后无统计学差异(P>0.05)。
第二部分
1、总体生存期及复发转移情况：治疗组中位总生存时间为30个月,平均总生存为37.38个月,中位DFS时间为30个月,平均DFS时间为37.19个月；对照组中位总生存时间为17个月,平均总生存为20.93个月,中位DFS时间为13个月,平均DFS时间为16.26个月。随访期内,共有12例患者发生疾病复发或转移,发生率在28.57%(12/42)；其中治疗组2例复发(2/21,9.52%),4例转移(4/21,19.05%)；对照组6例转移(6/21,28.57%)全部发生在16个月以内。经Log rank检验,两者的总生存率及无远处转移生存率的差异均有显著性(P值均为0.000)。
2、1.5年总生存率及复发转移率比较：治疗组1.5年总生存率为71.43%(15/21),对照组21例患者,1.5年总生存率为47.62%(10/21)；治疗组1.5年无疾病复发转移生存率为61.90%(13/21),对照组为19.05%(4/21)；1.5年复发转移率,治疗组为9.52%(2/21),对照组为28.57%(6/21)。
3、3年总生存率及复发转移率比较：3年总生存率,治疗组为42.86%(9/21),对照组为19.05%(4/21)；3年无疾病复发转移生存率,治疗组为38.10%(8/21),对照组为14.29%(3/21)；3年复发转移率,治疗组为4.76%(1/21),对照组无；
4、5年生存率与复发转移率比较：治疗组5年生存率28.57%(6/21),5年局部复发生存率为9.68%,对照组无随访时间达到或超过5年的观察病例。
5、复发转移的单因素分析显示：年龄、淋巴结数目与复发转移呈正相关性(P<0.05)；服用乳积方与复发转移呈负相关(P<0.05)。
6、死亡相关风险的单因素分析显示：年轻、未绝经、Her-2过表达型的乳腺癌相关死亡风险增加(P<0.05)；服用乳积方可以降低死亡风险,(P<0.05)。呈正相关的Kaplan-Meier检验提示：年龄、月经状态、免疫组化类型、分期、淋巴结数目、放疗、新辅助化疗等单因素对于生存期无影响(P>0.05)。
第一部分
1、乳积方辩证加减治疗激素受体阴性乳腺癌综合治疗后患者,可以明显减轻临床症状的作用。
2、乳积方能够改善化放疗后肝功能异常。
3、乳积方能够改善激素受体阴性乳腺癌患者综合治疗后的生存质量。
第二部分
1、乳积方辩证加减治疗激素受体阴性乳腺癌综合治疗后患者,能够延长总生存期及无疾病生存期。
2、乳积方辩证加减治疗激素受体阴性乳腺癌综合治疗后患者,能够延缓复发转移时间。
3、单因素分析显示：年龄、淋巴结数目与激素受体阴性乳腺癌综合治疗后复发转移风险呈正相关；年龄、月经状态与疾病相关死亡风险呈正相关。
4、单因素分析显示：服用乳积方能够显著降低激素受体阴性乳腺癌综合治疗后复发转移风险。
Under the chemotherapy、radiotherapy、biotherapy or targeted therapy, those patients with hormone receptors negative (HR-) breast cancer after surgical services, could gain a suvival time; while numbers of clincal study demonstrated that the patients with HR- breast cancer has shorter Disease-free Survival (DFS) and Overall Survival(OS) than hormone receptors positive patients. It is a plum in clincal study, that searching for the new method to prolong HR- patients'DFS and OS, and reduce the rate of recurrence and metastasis.
Traditional Chinese Medicine treatment based on the concept of wholism and categorical identification, could relieve the local symptom after surgry、the side-effect of chemotherapy and radiotherapy, regulate the internal environment of the body, in order to improve patients'quality of life, and prolong the median disease free survival.
The Ru Ji Fang prepared by our hospital,and in many years'clinical practice,we find that RujiFang could relieve clinical symptom、improve quality of life and survival time. There are not enough objective data to prove RujiFang's fanction, and our study will research RujiFang's prevention effection from the recurrence and metastasis for breast cancer patients with hormone receptors negative.
Objective
The study is to reveal RujiFang's therapy effection on clincal symptom、the quality of life、survival time and the time of tumors'recurrence and metastasis in hormone receptors negative breast cancer.
Methods
A retrospective analysis for a group of breast cancer patients. All patients accept a long-term of follow-up,and select about 42 qualified female cases with hormone receptors negative breast cancer and finished surgical thrapy. According to the treatment and medcine records in follow-up period,all patients divided into treated group and controled group.In treated group, patients after a combined treatment, need a RujiFang therapy more than 3 months; patients in controled group followed regularlly, but cannot accept any kinds of antieoplaston, include Chinese Anti-cancer Medicine. Before the study and after the final follow up, record the score of clinical symptom、laboratory、the scores of ECOG and quality of life (Functional Assessment of Cancer Therapy-Breast Cancer FACT-B),and the Overall Survival (OS)、the time of recurrence or metastasis, compared the difference in the interior-group and inter-group, to obtain the statically difference.
Results
PartⅠ
1、RujiFang is helpful to relieve the clinical sympotm for the patients with hormone receptors negative breast cancer:the total marked effective rate of treated group is 48%, effective rate is 52%, and a 100% total remission rate, compared with the controled group, could have statistical singnificance (P<0.05)
2、RujiFang has the funcation of improve abnormal liver function after chemotherapy, and compered with the controled group,could have statistical singnificance (P<0.05)
3、RujiFang can improve the patients' quality of life:
(1) PS(ECOG) score:compare the score before treatment, there was no significent difference between the two groups (P>0.05); after the study,the score of the treated group is lower than the controled group's, the difference have statistical sense (P<0.05); there is not significent change in the PS score before and after treatment (P>0.05), while in the controled group, after the treatment, the score was significantly higher than before (P<0.05)
(2) The results of FACT-B determination:there were no signifcant difference between two groups' scores before the study (P>0.05); in post-treatment, the scors of Physical Well-Being、Emotional Well-Being in the treated group are less than the control group's (P<0.05).Before and after the treatments, in the treated group, patients' Physical Well-Being and Emotional Well-Being have significantly improved (P<0.01); Social-Family Well-Being and Functional Well-Being are improved significantly (P<0.05); In control grou, the score of Functional Well-Being、Affixation Attention after treatment were markedly lower (P<0.05); Physical Well-Being、Emotional Well-Being、Social-Family Well-Being have no significantly change, before and after the treatment (P>0.05)
PartⅡ
1、FLF、FDM and OS:in the treated group, the median OS is 30 months, mean OS is 37.38 months, median DFS is 30 months, mean DFS is 37.19 months; in the controled group, the median OS is 17months, mean OS is 20.93 months, median DFS is 13 months, mean DFS is 16.26 months. During follow-up period, there are 12 cases'recurrence or metastases, incidence rate is 28.57%(12/42):2 casess'recurrence (2/21,28.57%) and 4 cases' metastases(4/21,19.05%), in the treated group; 6 cases' metastases(6/21,28.57%) and all happens in 16 months, in the control group. Comparison among groups there are significatly difference on the OS and DFS(Log rank test P=0.000).
2、The 1.5-year OS、1.5-year recurrence and metastsis rates:1.5- year OS:71.43% (the treated group 15/21) VS.47.62% (the controled group 10/21); the 1.5-year FLF and/or FDM:61.90%(the treated group 13/21) VS.19.05% (the controled group 4/21); the recurrence and metastasis rates for 1.5 years:9.52% (the treated group 2/21) VS.28.57% (the controled group 6/21).
3、The 3-year OS、FLF and FDM:the 3-year OS:42.86%(the treated group 9/21) VS.19.05% (the controled group 4/21); 3-year FLF and/or FDM:38.10% (the treated group 8/21) VS.14.29% (the control group 3/21); 3-year recurrence and metastasis rates:4.76% (the treated group 1/21),0 cases in the control group.
4、5-year OS、1.5-year recurrence and metastsis rates:in the treated group,5-year OS is 28.57% (6/21),5-year local recurrence rates is 9.68%; there were no case followed or beyond 5 years in the controled group. 5、The univariate analyses for the risk factors of recurrence and/or metastasis:age and the number of lymph nodes have positive correlation with the risk of recurrence and/or metastasis (P<0.05); and this kind of risk cuold be reduced by the therapy of RujiFang significantly (P<0.05). 6、The univariate analyses for the risk factors of death:The factors such as young、premenopausal、positive C-erbB-2 expression could increase the risk of Breast Cancer related death (P<0.05); and the therapy of RujiFang could reduce the risk of Breast Cancer related death (P<0.05).The Kaplan-Meier test show:those factors, such as age、menstrual state、immunohistochemical type、clinical TNM stage、the number of lymph nodes、rediotherapy、neoadjuvant chemotherapy,have no significantly influence to OS or DFS (P>0.05)
Conclusion
PartⅠ
1、RujiFang could relieve the clinical sympotm for the patients with hormone receptors negative breast cancer.
2、RujiFang could improve the chemotherapy and/or radiotherapy related abnormal liver function
3、RujiFang could improve the quality of life for the patients with hormone receptors negative breast cancer after complex treatment.
PartⅡ
1、RujiFang could prolong the OS and DFS of patients with hormone receptors negative breast cancer.
2、RujiFang for hormone receptors negative breast cancer patients, could delay the recurrence and/or metastasis time.
3、The univariate analyses show:age、the number of lymph nodes could increase the risk of recurrence and/or metastasis; age、premenopausal could increase the risk of hormone receptors negative Breast Cancer related death.
4、The univariate analyses show:RujiFang could significently reduce the recurrence and/or metastasis risk after the complex treatment for hormone receptors negative Breast Cancer pantients.
乳积方是本院自制中药方,多年的临床实践发现其在改善患者临床症状,改善生活质量,延长生存期等方面具有明显的疗效,但是目前尚缺乏循证医学的客观数据支持,所以,本研究将研究乳积方对于激素受体阴性乳腺癌术后患者在预防复发转移中的作用。
目的
本研究旨在揭示乳积方对于激素受体阴性乳腺癌综合治疗后的患者在临床症状、生存质量、生存时间、复发转移时间等方面的影响,探讨其预防乳腺癌术后复发转移的作用。方法
回顾性分析长期接受随访的42例激素受体阴性乳腺癌术后女性患者,根据随访用药治疗情况,分为治疗组和对照组,其中治疗组在综合治疗后至少服用乳积方3个月,对照组患者综合治疗后,不服用乳积方,不接受其他任何抗肿瘤治疗,仅进行定期随访。末次随访结束后,记录两组患者入组前与治疗后的临床症状评分(附表1)、肝肾功能、CEA、CA12-5、CA153、生存质量评分(乳腺癌患者生存质量测定表,FACT-B附表2)、总生存时间、复发转移时间等方面差异,并进行组间及组内比较,得出统计学差异。
结果
第一部分
1、乳积方能够改善激素受体阴性乳腺癌患者的临床症状：治疗组显效率为48%,有效率为52%,总体缓解率达到100%。临床症状的缓解率,与对照组比较,差异有统计学意义(P<0.05)；
2、乳积方能够改善化、放疗后肝功能的异常,与对照组比较差异有统计学意义(P<0.05)；
3、乳积方能够改善激素受体阴性乳腺癌患者的生活质量：
(1)PS评分：治疗前组间比较,差异无统计学意义(P>0.05)；治疗后,治疗组明显低于对照组,差异有统计学意义(P<0.05)；组内比较,治疗组治疗前后PS评分无明显波动(P>0.05),对照组有明显升高,差异有统计学意义(P<0.05)。
(2) FACT-B生命质量测定结果提示：治疗前各项指标组间比较,差异无统计学意义(P>0.05)；治疗后,治疗组生理不适、情感波动少于对照组,社会家庭功能、躯体功能情况好于对照组,差异均有统计学意义(P<0.05)。组内比较,治疗组,治疗后患者生理状况、情感状况有明显改善,差异有统计学意义(P<0.01)；社会家庭状况、功能状况有明显提高,差异有统计学意义(P<0.05)；对照组,治疗后的功能状况、附加关注较治疗前有明显减低,差异有统计学意义(P<0.05)；生理状况、社会家庭状况、情感状况治疗前后无统计学差异(P>0.05)。
第二部分
1、总体生存期及复发转移情况：治疗组中位总生存时间为30个月,平均总生存为37.38个月,中位DFS时间为30个月,平均DFS时间为37.19个月；对照组中位总生存时间为17个月,平均总生存为20.93个月,中位DFS时间为13个月,平均DFS时间为16.26个月。随访期内,共有12例患者发生疾病复发或转移,发生率在28.57%(12/42)；其中治疗组2例复发(2/21,9.52%),4例转移(4/21,19.05%)；对照组6例转移(6/21,28.57%)全部发生在16个月以内。经Log rank检验,两者的总生存率及无远处转移生存率的差异均有显著性(P值均为0.000)。
2、1.5年总生存率及复发转移率比较：治疗组1.5年总生存率为71.43%(15/21),对照组21例患者,1.5年总生存率为47.62%(10/21)；治疗组1.5年无疾病复发转移生存率为61.90%(13/21),对照组为19.05%(4/21)；1.5年复发转移率,治疗组为9.52%(2/21),对照组为28.57%(6/21)。
3、3年总生存率及复发转移率比较：3年总生存率,治疗组为42.86%(9/21),对照组为19.05%(4/21)；3年无疾病复发转移生存率,治疗组为38.10%(8/21),对照组为14.29%(3/21)；3年复发转移率,治疗组为4.76%(1/21),对照组无；
4、5年生存率与复发转移率比较：治疗组5年生存率28.57%(6/21),5年局部复发生存率为9.68%,对照组无随访时间达到或超过5年的观察病例。
5、复发转移的单因素分析显示：年龄、淋巴结数目与复发转移呈正相关性(P<0.05)；服用乳积方与复发转移呈负相关(P<0.05)。
6、死亡相关风险的单因素分析显示：年轻、未绝经、Her-2过表达型的乳腺癌相关死亡风险增加(P<0.05)；服用乳积方可以降低死亡风险,(P<0.05)。呈正相关的Kaplan-Meier检验提示：年龄、月经状态、免疫组化类型、分期、淋巴结数目、放疗、新辅助化疗等单因素对于生存期无影响(P>0.05)。
第一部分
1、乳积方辩证加减治疗激素受体阴性乳腺癌综合治疗后患者,可以明显减轻临床症状的作用。
2、乳积方能够改善化放疗后肝功能异常。
3、乳积方能够改善激素受体阴性乳腺癌患者综合治疗后的生存质量。
第二部分
1、乳积方辩证加减治疗激素受体阴性乳腺癌综合治疗后患者,能够延长总生存期及无疾病生存期。
2、乳积方辩证加减治疗激素受体阴性乳腺癌综合治疗后患者,能够延缓复发转移时间。
3、单因素分析显示：年龄、淋巴结数目与激素受体阴性乳腺癌综合治疗后复发转移风险呈正相关；年龄、月经状态与疾病相关死亡风险呈正相关。
4、单因素分析显示：服用乳积方能够显著降低激素受体阴性乳腺癌综合治疗后复发转移风险。
Under the chemotherapy、radiotherapy、biotherapy or targeted therapy, those patients with hormone receptors negative (HR-) breast cancer after surgical services, could gain a suvival time; while numbers of clincal study demonstrated that the patients with HR- breast cancer has shorter Disease-free Survival (DFS) and Overall Survival(OS) than hormone receptors positive patients. It is a plum in clincal study, that searching for the new method to prolong HR- patients'DFS and OS, and reduce the rate of recurrence and metastasis.
Traditional Chinese Medicine treatment based on the concept of wholism and categorical identification, could relieve the local symptom after surgry、the side-effect of chemotherapy and radiotherapy, regulate the internal environment of the body, in order to improve patients'quality of life, and prolong the median disease free survival.
The Ru Ji Fang prepared by our hospital,and in many years'clinical practice,we find that RujiFang could relieve clinical symptom、improve quality of life and survival time. There are not enough objective data to prove RujiFang's fanction, and our study will research RujiFang's prevention effection from the recurrence and metastasis for breast cancer patients with hormone receptors negative.
Objective
The study is to reveal RujiFang's therapy effection on clincal symptom、the quality of life、survival time and the time of tumors'recurrence and metastasis in hormone receptors negative breast cancer.
Methods
A retrospective analysis for a group of breast cancer patients. All patients accept a long-term of follow-up,and select about 42 qualified female cases with hormone receptors negative breast cancer and finished surgical thrapy. According to the treatment and medcine records in follow-up period,all patients divided into treated group and controled group.In treated group, patients after a combined treatment, need a RujiFang therapy more than 3 months; patients in controled group followed regularlly, but cannot accept any kinds of antieoplaston, include Chinese Anti-cancer Medicine. Before the study and after the final follow up, record the score of clinical symptom、laboratory、the scores of ECOG and quality of life (Functional Assessment of Cancer Therapy-Breast Cancer FACT-B),and the Overall Survival (OS)、the time of recurrence or metastasis, compared the difference in the interior-group and inter-group, to obtain the statically difference.
Results
PartⅠ
1、RujiFang is helpful to relieve the clinical sympotm for the patients with hormone receptors negative breast cancer:the total marked effective rate of treated group is 48%, effective rate is 52%, and a 100% total remission rate, compared with the controled group, could have statistical singnificance (P<0.05)
2、RujiFang has the funcation of improve abnormal liver function after chemotherapy, and compered with the controled group,could have statistical singnificance (P<0.05)
3、RujiFang can improve the patients' quality of life:
(1) PS(ECOG) score:compare the score before treatment, there was no significent difference between the two groups (P>0.05); after the study,the score of the treated group is lower than the controled group's, the difference have statistical sense (P<0.05); there is not significent change in the PS score before and after treatment (P>0.05), while in the controled group, after the treatment, the score was significantly higher than before (P<0.05)
(2) The results of FACT-B determination:there were no signifcant difference between two groups' scores before the study (P>0.05); in post-treatment, the scors of Physical Well-Being、Emotional Well-Being in the treated group are less than the control group's (P<0.05).Before and after the treatments, in the treated group, patients' Physical Well-Being and Emotional Well-Being have significantly improved (P<0.01); Social-Family Well-Being and Functional Well-Being are improved significantly (P<0.05); In control grou, the score of Functional Well-Being、Affixation Attention after treatment were markedly lower (P<0.05); Physical Well-Being、Emotional Well-Being、Social-Family Well-Being have no significantly change, before and after the treatment (P>0.05)
PartⅡ
1、FLF、FDM and OS:in the treated group, the median OS is 30 months, mean OS is 37.38 months, median DFS is 30 months, mean DFS is 37.19 months; in the controled group, the median OS is 17months, mean OS is 20.93 months, median DFS is 13 months, mean DFS is 16.26 months. During follow-up period, there are 12 cases'recurrence or metastases, incidence rate is 28.57%(12/42):2 casess'recurrence (2/21,28.57%) and 4 cases' metastases(4/21,19.05%), in the treated group; 6 cases' metastases(6/21,28.57%) and all happens in 16 months, in the control group. Comparison among groups there are significatly difference on the OS and DFS(Log rank test P=0.000).
2、The 1.5-year OS、1.5-year recurrence and metastsis rates:1.5- year OS:71.43% (the treated group 15/21) VS.47.62% (the controled group 10/21); the 1.5-year FLF and/or FDM:61.90%(the treated group 13/21) VS.19.05% (the controled group 4/21); the recurrence and metastasis rates for 1.5 years:9.52% (the treated group 2/21) VS.28.57% (the controled group 6/21).
3、The 3-year OS、FLF and FDM:the 3-year OS:42.86%(the treated group 9/21) VS.19.05% (the controled group 4/21); 3-year FLF and/or FDM:38.10% (the treated group 8/21) VS.14.29% (the control group 3/21); 3-year recurrence and metastasis rates:4.76% (the treated group 1/21),0 cases in the control group.
4、5-year OS、1.5-year recurrence and metastsis rates:in the treated group,5-year OS is 28.57% (6/21),5-year local recurrence rates is 9.68%; there were no case followed or beyond 5 years in the controled group. 5、The univariate analyses for the risk factors of recurrence and/or metastasis:age and the number of lymph nodes have positive correlation with the risk of recurrence and/or metastasis (P<0.05); and this kind of risk cuold be reduced by the therapy of RujiFang significantly (P<0.05). 6、The univariate analyses for the risk factors of death:The factors such as young、premenopausal、positive C-erbB-2 expression could increase the risk of Breast Cancer related death (P<0.05); and the therapy of RujiFang could reduce the risk of Breast Cancer related death (P<0.05).The Kaplan-Meier test show:those factors, such as age、menstrual state、immunohistochemical type、clinical TNM stage、the number of lymph nodes、rediotherapy、neoadjuvant chemotherapy,have no significantly influence to OS or DFS (P>0.05)
Conclusion
PartⅠ
1、RujiFang could relieve the clinical sympotm for the patients with hormone receptors negative breast cancer.
2、RujiFang could improve the chemotherapy and/or radiotherapy related abnormal liver function
3、RujiFang could improve the quality of life for the patients with hormone receptors negative breast cancer after complex treatment.
PartⅡ
1、RujiFang could prolong the OS and DFS of patients with hormone receptors negative breast cancer.
2、RujiFang for hormone receptors negative breast cancer patients, could delay the recurrence and/or metastasis time.
3、The univariate analyses show:age、the number of lymph nodes could increase the risk of recurrence and/or metastasis; age、premenopausal could increase the risk of hormone receptors negative Breast Cancer related death.
4、The univariate analyses show:RujiFang could significently reduce the recurrence and/or metastasis risk after the complex treatment for hormone receptors negative Breast Cancer pantients.
引文
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