乳腺癌蒽环类新辅助化疗疗效与ER、PR、HER2表达的关系

目的探讨乳腺癌蒽环类新辅助化疗疗效与ER、PR、HER2表达的关系。方法乳腺癌患者在接受蒽环类方案新辅助化疗前用免疫组化法检测乳腺癌组织中ER、PR和HER2的表达情况,新辅助化疗3周期结束后进行疗效评价,分析它们之间的关系。结果ER和PR阴性表达组47例,有效率为80．85％;其中PCR率为23．40％。ER和（或）PR阳性表达组43例,有效率为60．47％;其中PCR为6．98％。两组有效率及PER率比较,差异有统计学意义（P〈0．05）。HER2阳性表达组32例,有效率为65．63％;其中PCR率为12．50％。HER2阴性表达组58例,有效率为74．14％;其中PCR率为17．24％。两组有效率及PCR率比较,差异无统计学意义（P〉0．05）。结论激素受体双阴者可能较单阳或双阳者对蒽环类方案化疗的敏感性更高。尤其是激素受体双阴者的PCR率明显高于单阳或双阳者。     

腋窝淋巴结阳性乳腺癌中多西他赛序贯吡柔比星/环磷酰胺应用的临床观察

目的观察多西他赛序贯吡柔比星/环磷酰胺在腋窝淋巴结阳性乳腺癌辅助化疗中的应用。方法收集41例病理证实的腋窝淋巴结阳性的乳腺癌术后患者,予多西他赛序贯吡柔比星/环磷酰胺治疗,记录和分析治疗过程发生的毒不良反应。结果全组41例病例,有37例完成化疗,血液学毒性主要表现为白细胞的下降;非血液学毒性主要为脱发和胃肠道反应;其他包括转氨酶升高、心脏毒性及周围神经毒性等,经对症治疗后,所有毒不良反应均能缓解。结论多西他赛序贯吡柔比星/环磷酰胺在腋窝淋巴结阳性乳腺癌辅助化疗的临床应用中不良反应可耐受。     

Protective effects of nebivolol against anthracycline-induced cardiomyopathy: A randomized control study

Background

We aimed to evaluate the effect of prophylactic nebivolol use on prevention of antracycline-induced cardiotoxicity in breast cancer patients.

Methods

In this small, prospective, double-blind study, we randomly assigned 45 consecutive patients with breast cancer and planned chemotheraphy to receive nebivolol 5 mg daily (n = 27) or placebo (n = 18). Echocardiographic measurements and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels were obtained at baseline and at 6-month of chemotherapy.

Results

Both studied groups had comparable echocardiographic variables and NT-pro-BNP levels at baseline. At 6-month, the left ventricular (LV) end-systolic and end-diastolic diameters increased in the placebo group (LVESD: 29.7 ± 3.4 to 33.4 ± 4.5 mm; LVEDD: 47.2 ± 3.8 to 52.0 ± 4.6 mm, p = 0.01 for both) but remained unchanged in the nebivolol group (LVESD: 30.4 ± 3.5 to 31.0 ± 3.6 mm, p = 0.20; LVEDD: 47.0 ± 4.4 to 47.1 ± 4.0 mm, p = 0.93). The placebo group also had lower LVEF than the nebivolol group (57.5 ± 5.6% vs. 63.8 ± 3.9%, p = 0.01) at 6-month. NT-pro-BNP level remained static in the nebivolol group (147 ± 57 to 152 ± 69 pmol/l, p = 0.77) while it increased in the placebo group (144 ± 66 to 204 ± 73 pmol/l, p = 0.01).

Conclusions

Prophylactic use of nebivolol treatment may protect the myocardium against antracycline-induced cardiotoxicity in breast cancer patients.     

替吉奥联合多西他赛治疗蒽环类药物耐药的复发转移性乳腺癌的临床观察

目的：观察替吉奥胶囊联合多西他赛治疗蒽环类药物耐药的复发转移性乳腺癌的疗效及安全性。方法：31例女性复发转移性乳腺癌患者均给予多西他赛75mg／m2,d1。从给予多西他赛治疗前一天开始,给予口服地塞米松8mg,bid,连用3～5d;替吉奥胶囊80mg／m2,早、晚饭后各服1次,d1～d14。3周为1个周期,2个周期后评价疗效及毒性反应,随访12个月。结果：所有患者接受至少2个周期的治疗后总有效率为48．4％,临床获益率为65．5％;主要毒性反应为血液学毒性和消化道反应,且所有患者均未见明显心、肾毒性。随访12个月,24例存活,生存率为77．4％。结论：替吉奥胶囊联合多西他赛治疗蒽环类药物耐药的复发转移性乳腺癌疗效显著,且安全性较好。     

新辅助化疗对ⅡB期乳腺癌的疗效对比研究

目的研究新辅助化疗治疗ⅡB期乳腺癌的临床作用。方法选取2002年1月至2004年11月ⅡB期女性乳腺癌330例,全部单侧患病,随机分成2组。新辅助化疗组152例（年龄32～73岁,平均42．6岁;左侧78例,右侧74例）,给予紫杉类、蒽环类为主的联合化疗,每2个周期后评价疗效,4个周期后实施手术。非新辅助化疗组178例（年龄31～72岁,平均41．4岁;左侧98例,右侧80例）。2组均根据肿瘤大小,行保乳手术或行乳腺癌改良根治术。根据“国际抗癌联合会标准”对乳腺癌原发病灶和区域淋巴结新辅助化疗后的临床缓解情况进行评估。结果新辅助化疗组总有效率为91．45％,保乳比例为44．70％,对照组保乳比例为21．90％。新辅助化疗组的3年和5年生存率分别为96．05％和75．00％,显著高于非新辅助化疗组。结论新辅助化疗可有效的降低ⅡB期乳腺癌临床分期,提高保乳的可行性和术后生存率。     

TOP2A amplification in the absence of that of HER-2/neu: toward individualization of chemotherapeutic practice in breast cancer

Primary objective.

To investigate the relationship between human epidermal growth factor receptor (HER)-2/neu and the gene encoding topoisomerase IIα (TOP2A) in breast cancer, while elucidating their association with clinicopathological variables.

Methods.

Real-time quantitative polymerase chain reaction (RQ-PCR) was performed on a 96-patient study group to assess gene amplification, and levels were determined using the comparative cycle threshold approach and Taqman assays. An immunohistochemistry (IHC) microarray (n = 76) was then employed to check for correlation between gene amplification and protein expression levels.

Results.

Amplification levels of TOP2A did not differ significantly according to HER-2/neu status by either RQ-PCR or IHC microarray. Of the HER-2/neu⁻ patients, 29.1% demonstrated levels of TOP2A above the third quartile, whereas 22.9% of the HER-2/neu⁺ patients had values in the first quartile (log TOP2A <0.62), thereby indicating low-level amplification. Of the 60 patients characterized as HER-2/neu⁻ using IHC and fluorescence in situ hybridization (FISH), 22.9% were classified as TOP2A⁺ on the IHC microarray. Of the 14 patients deemed HER-2/neu⁺ using IHC and FISH, meanwhile, the majority (n = 10) were classified as TOP2A⁺.

Conclusions.

Our results indicate that amplification of TOP2A in breast cancer is not confined to those who are concomitantly HER-2/neu⁺, and suggest that a significant proportion of HER-2/neu⁻ patients exhibit high levels of TOP2A.     

蒽环类药物对乳腺癌患者月经状态的影响

目的研究乳腺癌患者年龄及不同蒽环类化疗药物对化疗诱导停经的影响,为临床合理用药提供依据。方法前瞻性研究绝经前乳腺癌患者接受化疗后月经变化情况,比较不同年龄段及使用不同化疗药物的患者月经状态变化的差异。结果137例乳腺癌患者,化疗致闭经（CIA）的发生率为73．72％（101／137）,长期闭经（LCIA）发生率为43．80％（60／137）。40岁以下患者CIA和LCIA的发生率均显著低于40岁以上的患者（X^2=25．32、18．42,P〈0．05）,并且40岁以下组发生CIA后月经恢复率为61．90％（13／21）,明显高于40岁以上组的35．00％（28／80）,差异有统计学意义（X^2=4．99,P=0．025）。40岁以上患者中表柔比星（商品名：法玛新）、表柔比星（商品名：艾达生）、吡柔比星诱导LCIA率差异有统计学意义（X^2=6．92,P=0．031）。结论年龄是CIA的重要因素,40岁以下患者月经受化疗影响较小,停经多为可逆性。40岁以上患者使用不同的蒽环类化疗药物对月经状态的影响差异有统计学意义。     

Effects of age on multidrug resistance protein expression and doxorubicin accumulation in cardiac and skeletal muscle

Abstract

1. Doxorubicin (DOX) is a highly effective and commonly used anthracycline antibiotic used to treat cancer patients. The side effects of DOX are manifested in a more delayed manner in children and multidrug resistant proteins (MRPs) may factor into this phenomenon. MRPs are known to extrude DOX and may factor into the degree of cardiac DOX accumulation.

2. The purpose of this study was to examine age-related differences in muscle MRP expression and DOX accumulation.

3. Female Sprague–Dawley rats were randomly selected to receive a 15-mg DOX/kg body weight bolus injection (i.p.) at various ages.

4. Cardiac and extensor digitorum longus DOX accumulation was markedly increased as animals aged from 4 to 24 weeks. In contrast, no differences in soleus accumulation were observed. A significant age-related reduction in MRP-2 and MRP-7 expression was detected in cardiac and extensor digitorum longus tissues with no age differences in MRP-1 expression in any tissues analyzed. MRP-6 was not detected in any tissues.

5. These data suggest that aging is associated with increased DOX accumulation and an age-related decrease in MRP expression may be a factor.     

幼儿急性早幼粒细胞白血病1例并文献复习

目的探讨幼儿急性早幼粒细胞白血病的临床特点、治疗难点所在,加深对这一亚类的白血病的认识,提高救治效率。方法报道1例经全反式维甲酸治疗缓解的幼儿急性早幼粒细胞白血病病例,并结合文献总结这一类疾病的发病和治疗特点。结果尽管这一亚类的白血病经过常规的诱导缓解方案能够获得满意疗效,但护理难度大、依从性差,会给临床治疗带来较大的障碍。结论幼儿APL采用规范化的治疗可以获得良好的治疗效果,重要的是要增强其对治疗的依从性,鼓励其接受正规方案的治疗,避免转变成为复发难治型。     

Docetaxel and epirubicin salvage regimen in relapsed anthracycline-sensitive metastatic breast cancer patients after anthracycline-containing adjuvant therapy

Summary  Our aim in this paper is to verify the efficacy and safety of a epirubicin and docetaxel salvage regimen for anthracycline sensitive metastatic breast cancer patients who have relapsed after anthracycline-containing adjuvant therapy. Thirty-two metastatic breast cancer patients were treated with epirubicin and docetaxel every 21 days. Of the 31 evaluable patients, there were 13/31 (41.9%) partial responses and no complete responses. Median time to progression was 12 months (95% CI, 4–60 months) and median survival duration was 41 months (95% CI, 1.2–80.8 months). According to the Cox model, ECOG performance and response group were statistically significant variables, and visceral metastasis was a borderline significant variable with regards to overall survival. Although this salvage regimen showed a high rate of hematologic toxicities, it was a relatively active regimen with manageable toxicities and no cardiac dysfunction. We propose that this salvage regimen could be carefully used in anthracycline sensitive metastatic breast cancer patients who have relapsed after anthracycline-containing adjuvant therapy.