Use of aromatase inhibitors in postmenopausal women with advanced breast cancer

Surgeons have been involved in the management of metastatic breast cancer since the technique of ovarian ablation was introduced in 1896. However, as newer hormonal and chemotherapeutic regimens were developed, drug therapy gradually replaced surgery as the preferred treatment for metastatic breast cancer. Thus, management of metastatic breast cancer has largely shifted from surgeons to medical oncologists. Advances in hormonal pharmacology have placed hormonal therapy alongside surgery and radiation therapy as a standard treatment option for women with advanced breast cancer. The purpose of this article is to update surgeons on the current use of hormonal agents for treatment of advanced breast cancer in postmenopausal women, and to review the aromatase inhibitors, a new line of hormonal agents for the treatment of advanced breast cancer. J. Surg. Oncol. 1997;66:215–220. © 1997 Wiley-Liss, Inc.     

托瑞米芬治疗乳腺囊性增生症临床疗效的初步观察

为了观察托瑞米芬(枢瑞)治疗乳腺囊性增生症的临床疗效。选取临床症状及体征均明显的乳腺囊性增生 症100例,试验组(50例)给予托瑞米芬40mg口服,1次/d,连用3个月,并根据乳腺活检后ER结果分成ER(+)及 ER(-)两个亚组观察其临床疗效。对照组(50例)给予中成药(乳癖散结胶囊)对症治疗,连用3个月。托瑞米芬治 疗乳腺囊性增生症的临床有效率为80%(40/50),对ER(+)患者疗效更高,有效率92.9%(26/28)。无明显的毒副 反应。乳癖散结胶囊对照组临床有效率为58%(29/50),两组比较差异有统计学意义,0.01相似文献   

隐匿性乳腺癌的诊断和治疗

目的:探讨隐匿性乳腺癌(occultbreast cancer,OBC)的发病特点、诊断和治疗方法。方法:回顾性分析21例OBC的临床、病理资料及随访结果。结果:21例均以腋下肿块为首发症状且均行手术治疗及术后综合治疗,5年生存率为78·70%,与我院同期乳腺癌5年总生存率75·94%(2099/2764)相似。结论:对原因不明的腋下肿块,应考虑到OBC的可能,同时应予切除并送检病理确诊。一经确诊,宜选择乳腺癌根治术或改良根治术,并予辅助性放疗、化疗。肿瘤防治杂志,2005,12(19):1497-1498     

隐匿性乳腺癌的诊断和治疗

目的：探讨隐匿性乳腺癌（occult breast cancer,OBC）的发病特点、诊断和治疗方法.方法：回顾性分析21例OBC的临床、病理资料及随访结果.结果：21例均以腋下肿块为首发症状且均行手术治疗及术后综合治疗,5年生存率为78.70%,与我院同期乳腺癌5年总生存率75.94%（2 099/2 764）相似.结论：对原因不明的腋下肿块,应考虑到OBC的可能,同时应予切除并送检病理确诊.一经确诊,宜选择乳腺癌根治术或改良根治术,并予辅助性放疗、化疗.     

microRNA-21对乳腺癌MCF-7/ADR细胞株多柔比星耐药性影响的研究

目的:探讨microRNA-21(miR-21)基因表达改变对乳腺癌细胞多柔比星化疗耐药的影响.方法:人工合成miR-21模拟序列或干扰序列,以脂质体为载体,转染乳腺癌细胞MCF-7及其多柔比星耐药细胞株MCF-7/ADR;应用荧光定量RT-PCR检测miR-21的表达;应用MTT法检测细胞转染前后对多柔比星的耐药性;应用流式细胞仪检测细胞凋亡;应用蛋白质印迹法检测PTEN、BAX及Bcl-2蛋白的表达.结果:MTT检测结果示,MCF-7及其耐药株MCF-7/ADR细胞多柔比星半数抑制浓度(IC50)分别为(0.28±0.03)和(17.5±0.12) μmol/L.miR-21表达上调,MCF-7细胞对多柔比星的IC50明显增高为(3.65±0.12) μmol/L;miR-21表达下调,MCF-7/ADR细胞对多柔比星的IC50明显降低为(7.53±0.11) μmol/L.流式细胞分析显示,miR-21下调后MCF-7/ADR细胞凋亡率明显增加.同时,细胞内PTEN、BAX蛋白表达水平增加,Bcl-2表达降低.结论:miR-21在乳腺癌化疗耐药中具有重要作用,抑制miR-21的表达可以逆转乳腺癌多柔比星耐药细胞株对多柔比星的耐药性.     

卡培他滨单药治疗蒽环类和紫杉醇类耐药的晚期乳腺癌25例

为了观察卡培他滨单药治疗蒽环类和紫杉醇类耐药晚期乳腺癌的临床疗效和毒副作用,对以蒽环类及紫杉醇类为基础的化疗方案耐药的晚期乳腺癌25例,应用卡培他滨2 500 mg/(m2.d),口服14 d,21 d为1个周期,观察临床疗效和毒副反应。结果:共化疗112个周期,肿瘤缓解率24%(6/25),临床受益率56%(14/25),中位肿瘤进展时间3.9个月(1~17个月),中位生存期10个月(2.5~>24个月)。Ⅲ、Ⅳ度毒副反应有:Ⅲ度手足综合征3例(12%),Ⅲ度白细胞下降2例(8%),Ⅲ度腹泻1例(4%),Ⅳ度恶心、呕吐1例(4%)。初步研究结果提示,卡培他滨单药化疗蒽环类和紫杉醇类耐药的晚期乳腺癌,疗效确切、毒副反应轻、应用方便。     

HER-2 RNA干扰对HER-2阳性乳腺癌化疗敏感性的研究

目的:探讨HER-2 RNA干扰(RNAi)对HER-2阳性乳腺癌细胞的化疗敏感性的影响.方法:构建能够表达HER-2siRNA的质粒栽体,利用载体转染HER-2阳性乳腺癌细胞SKBR-3,RT-PCR与蛋白质印迹法检测HER-2 mRNA与蛋白表达,受转染的细胞与不同浓度的化疗药物表柔比星共培养,MTT法检测细胞活性.结果:SKBR-3细胞HER-2基因受到RNAi后,HER-2 mRNA及蛋白表达分别下降约60%与55%,细胞活性出现明显下降,肿瘤细胞对表柔比星的半数抑制浓度(IC50)为0.25 μg/μL,相较对照组而言,化疗敏感性提高明显.结论:乳腺癌HER-2是理想的RNA干扰治疗靶点,靶向HER-2的RNAi可以抑制肿瘤细胞生长,而且能够增加肿瘤细胞化疗敏感性.     

健择联合卡培他滨治疗晚期乳腺癌55例临床观察

为观察及评价盐酸吉西他滨(健择)联合卡培他滨(希罗达)治疗复发转移性乳腺癌的疗效和不良反应,武汉钢铁集团公司第二职工医院肿瘤中心对55例晚期乳腺癌患者均给予健择1000mg/m2,静脉滴入,d1、d8;希罗达口服,2次/d,餐后服用,每次1000mg/m2,连续服用14d;治疗周期为21d,至少治疗2个周期。结果完全缓解(CR)7例,部分缓解(PR)30例,稳定(SD)15例,疾病进展(PD)3例,总有效率67.3%,中位TTP6.5个月。不同转移部位或器官的有效率分别为:胸壁83.3%(15/18),淋巴结80.0%(20/25),肺脏75.0%(15/20),骨骼41.7%(5/12),肝脏28.0%(7/25)。Ⅰ、Ⅱ级不良反应为皮肤色素沉着40例,手足综合征35例,恶心呕吐30例,腹泻25例,白细胞下降40例,Ⅲ、Ⅳ级不良反应为白细胞下降7例,恶心呕吐3例,贫血3例。初步观察结果提示,健择联合希罗达治疗晚期乳腺癌疗效肯定,患者耐受性良好。     

不同剂量强度蒽环类化疗药物对乳腺癌患者心脏毒性的临床观察

探讨蒽环类化疗药物剂量强度与心脏耐受性的关系,对68例局部晚期乳腺癌患者应用不同剂量强度的CEF(5-FU 表阿霉素 环磷酰胺)联合化疗方案,通过检测患者心电图及心功能的变化,临床对照观察患者的心脏毒性反应。表阿霉素低剂量(50mg/m2)组较少出现心电图异常,3例心电图一过性改变者,较快(2周内)恢复正常。高剂量组(75mg/m2)5例心电图改变,有3例在2周内恢复正常,1例有所减轻,但1例在2周后无改善,后经超声心动图检测诊为充血性心力衰竭。初步研究结果提示,大多数患者能够较好地耐受高剂量的CEF化疗方案。     

乳腺癌手术方式对女性性功能影响的初步对照分析

目的：研究乳腺癌术式对乳腺癌患者性功能的影响。方法：选择152乳腺癌手术患者（其中改良根治术113例数,简称改良根治组;保留乳房手术患者39名,简称保乳组）和47例乳腺良性疾病组患者（对照组）,采用乳腺癌术后性生活质量调查问卷评估乳癌改良根治术和保乳手术术式对乳腺癌患者术后性功能的影响。结果：三组之间性功能障碍率差异显著（P〈0．01）,改良根治组性欲低下率、性厌恶率、性唤起障碍率、性高潮障碍程度、性交疼痛程度显著高于保乳组及对照组（P〈0．01）,保乳术组性欲低下、性厌恶、性交痛、性唤起障碍率显著高于对照组（P〈0．01）。结论：乳腺癌手术对乳腺癌患者性功能具有重要影响,与保乳术相比,改良根治术对乳腺癌患者性功能的影响更为显著。     

Phase II study of sequential hormonal therapy with anastrozole/exemestane in advanced and metastatic breast cancer

Hormonal therapy is the preferred systemic treatment for recurrent or metastatic, post-menopausal hormone-receptor-positive breast cancer. Previous studies have shown that there is no cross-resistance between exemestane and reversible aromatase inhibitors. Exposure to hormonal therapy does not hamper later response to chemotherapy. Patients with locally advanced or metastatic, hormonal receptor positive or unknown, breast cancer were treated with oral anastrozole, until disease progression, followed by oral exemestane until new evidence of disease progression. The primary end point of the study was clinical benefit, defined as the sum of complete responses (CR), partial responses (PR) and > 24 weeks stable disease (SD). In all, 100 patients were enrolled in the study. Anastrozole produced eight CR and 19 PR for an overall response rate of 27% (95% CI: 18.6-36.8%). An additional 46 patients had long-term (> 24 weeks) SD for an overall clinical benefit of 73% (95% CI: 63.2-81.4). Median time to progression (TTP) was 11 months (95% CI: 10-12). A total of 50 patients were evaluated for the second-line treatment: exemestane produced one CR and three PR; 25 patients had SD which lasted > or = 6 months in 18 patients. Median TTP was 5 months. Toxicity of treatment was low. Our study confirms that treatment with sequential hormonal agents can extend the period of time during which endocrine therapy can be used, thereby deferring the decision to use chemotherapy.     

Oral, injected and implanted contraceptives and breast cancer risk among U.S. Hispanic and non-Hispanic white women

Associations between oral contraceptive (OC) use and breast cancer have been reported, but few studies have considered associations in racial and ethnic minorities. Data regarding injected or implanted hormonal contraceptives are limited. In a case-control study of Hispanic (796 cases, 919 controls) and non-Hispanic white (1,522 cases, 1,596 controls) women in the U.S. southwest interviewed in 2000-2005, 49% of Hispanic controls and 66% of non-Hispanic white controls reported having used OC. Breast cancer odds ratios (OR) associated with OC use within the past 5 years were 1.22 (95% confidence interval (CI) 0.80, 1.84) among Hispanics, 1.28 (95% CI 0.93, 1.76) among non-Hispanic whites, 1.27 (95% CI 0.99, 1.63) for both ethnic groups combined and 1.53 (95% CI 0.98, 2.40) for estrogen receptor (ER) negative tumors. OC use for 20 years or longer was associated with ORs of 1.50 (95% CI 1.04, 2.17) for both ethnic groups combined, and 2.23 (95% CI 1.17, 4.25) for ER negative tumors. Hormonal contraceptive injections were used by 3.3% of Hispanic controls and 2.8% of non-Hispanic white controls, OR 1.23 (95% CI 0.88, 1.73). Fifteen cases and 2 controls reported use of a subdermal contraceptive implant, OR 8.59 (95% CI 1.92, 38.39). Associations between OC use and breast cancer in Hispanics are consistent with modestly increased risk among recent users and for ER negative tumors, as observed in other populations. Based on a small number of users of contraceptive implants, a significantly increased breast cancer risk was observed; continued surveillance of implant users may be warranted.     

Cyclophosphamide,methotrexate, and fluorouracil; oral cyclophosphamide; levamisole; or no adjuvant therapy for patients with high‐risk,premenopausal breast cancer

BACKGROUND:

The Danish Breast Cancer Cooperative Group (DBCG) 77B trial examined the relative efficacy of levamisole, single‐agent oral cyclophosphamide, and the classic combination of cyclophosphamide, methotrexate, and 5‐fluorouracil (CMF) against no adjuvant systemic therapy in high‐risk breast cancer patients. The authors report the results from that trial after a potential follow‐up of 25 years.

METHODS:

Between 1977 and 1983, 1146 premenopausal patients who had tumors >5 cm or positive axillary lymph nodes were assigned randomly to 1 of 4 options: no systemic therapy, levamisole 5 mg weekly for 48 weeks (the levamisole arm), oral cyclophosphamide 130 mg/m² on Days 1 through 14 every 4 weeks for 12 cycles (the C arm), or oral cyclophosphamide 80 mg/m² on Days 1 through 14 plus methotrexate 30 mg/m² and fluorouracil 500 mg/m² intravenously on Days 1 and 8 every 4 weeks for 12 cycles (the CMF arm).

RESULTS:

The 10‐year invasive disease‐free survival (IDFS) rate was 38.6% in the control arm compared with 55.5% in the C arm, 48.8% in the CMF arm, and 35.2% in the levamisole arm. Compared with the control arm, the hazard ratio for an IDFS event was 0.62 in the C arm (P = .001) and 0.70 in the CMF arm (P = .01). The hazard ratio for death was 0.70 in both the C arm (P = .02) and the CMF arm (P = .02) at 10 years, and the overall survival (OS) benefit was maintained during 25 years of follow‐up. No significant differences were observed in IDFS or OS between the C arm and the CMF arm or between the levamisole arm and the control arm.

CONCLUSIONS:

Compared with controls, both cyclophosphamide and CMF significantly improved disease‐free survival and OS, and the benefits persisted for at least 25 years in premenopausal patients who had high‐risk breast cancer. Cancer 2010. © 2010 American Cancer Society.     

Tamoxifen and risk of large bowel cancer in women with breast cancer

Background: The increasingly consistent association between estrogen replacement therapy and colorectal cancer suggests that the anti-estrogen tamoxifen may also be associated with large bowel cancer incidence.Methods: Women with new diagnoses of breast cancer were identified from the Surveillance Epidemiology and End Results (SEER) Program, a set of geographically defined, population based cancer registries representing approximately ten percent of the U.S. population. Of 85,411 women with local or regional breast cancer diagnosed from 1983–90, 14,984 women were reported to have received hormonal therapy and 70,427 were not known to have received hormonal therapy. Subsequent cancer diagnoses were identified in this cohort beginning 6 months after initial breast cancer diagnosis until death, or December 31, 1994. Multivariate Cox proportional hazards models were used to estimate the risk of developing colorectal cancer and other second cancers according to hormonal therapy use.Results: Over the follow-up period 793 colorectal, 2,648 contralateral breast, 506 endometrial, 250 ovarian, 98 gastric, and 1,765 other cancers were identified in the study cohort. While overall there was no association between hormonal therapy use and colorectal cancer (relative risk (RR) 1.09, 95% confidence interval (CI) 0.88–1.35), in the period five or more years after diagnosis, risk was increased significantly by about 50% (95% CI 1.00–2.15). As expected, based upon clinical trials data, cancers of the contralateral breast were significantly decreased, and cancers of the uterine endometrium were significantly increased. No other meaningful associations were observed. When women were excluded for whom hormonal therapy might represent therapy other than tamoxifen (premenopausal women and those who received chemotherapy), this did not meaningfully alter these estimates.Conclusions: The results of this large population based cohort study suggest that tamoxifen therapy may modestly increase risk of large bowel cancer in women, but only after 5 years following initiation of breast cancer therapy.     

乳腺癌联合化疗患者凝血功能检测临床意义的探讨

为了探讨乳腺癌患者化疗时凝血参数的动态变化及临床意义,检测100例乳腺癌经手术患者化疗前后的凝血酶原时间(PT)、活化的部分凝血活酶时间(APTT)、纤维蛋白原含量(FIB)、凝血酶时间(TT),并与100例健康体检者和良性肿瘤患者进行对比分析。观察患者化疗前后凝血指标的变化,比较组间和组内的差异。乳腺癌患者化疗前与对照组比较,PT、APTT和TT差异均无统计学意义(P>0.05),而FIB含量明显高于对照组,P<0.05。乳腺癌患者在化疗过程中PT和APTT无明显变化,与化疗前比较差异无统计学意义,P>0.05;而FIB含量化疗后比化疗前逐渐升高,差异有统计学意义,P<0.05。TT化疗后与化疗前对比逐渐缩短,差异有统计学意义,P<0.05。乳腺癌患者凝血指标的定期监测可能是判断乳腺癌预后以及化疗后复发和转移的有价值指标。     

An open-label study of the effects of bupropion SR on fatigue, depression and quality of life of mixed-site cancer patients and their partners

This preliminary study investigated whether bupropion sustained release (SR) improved symptomatic fatigue, depression and quality of life in cancer patients and caregiver quality of life. The sample consisted of a prospective open case series of 21 cancer patients, with fatigue and with or without depression at moderate to severe levels, referred for psychiatric assessment from a tertiary care cancer centre. Both patient symptom ratings and caregiver ratings were measured before and after 4 weeks of treatment with the maximally tolerated dose of bupropion in the range of 100-300 mg per day. At trial completion, significant improvement was found for symptoms of fatigue and depression. Subjects were divided into two groups: depressed and non-depressed (based on a cut-off score of 17 on the Hamilton Depression Rating Scale). Both groups reported improvement for fatigue and depressive symptoms. Depressed subjects and their caregivers did not experience any change in quality of life, while the non-depressed subjects and their caregivers reported improvements. Results from this small group of patients suggest that bupropion may have potential as an effective pharmaceutical agent for treating cancer-related fatigue. A randomized, placebo-controlled trial with this medication is indicated.     

早期乳腺癌辅助内分泌治疗的原则与临床应用策略

辅助内分泌治疗早期乳腺癌大大提高了患者的长期生存率，业已成为激素受体阳性乳腺癌患者最重要的治疗手段。本文结合近年来的文献，对乳腺癌辅助内分泌的原则和策略作一介绍和评述。     

不同剂量强度蒽环类化疗药物对乳腺癌患者心脏毒性的临床观察

探讨蒽环类化疗药物剂量强度与心脏耐受性的关系,对68例局部晚期乳腺癌患者应用不同剂量强度的CEF（5-FU＋表阿霉素十环磷酰胺）联合化疗方案,通过检测患者心电图及心功能的变化,临床对照观察患者的心脏毒性反应.表阿霉素低剂量（50 mg/m^2）组较少出现心电图异常,3例心电图一过性改变者,较快（2周内）恢复正常.高剂量组（75 mg/m^2）5例心电图改变,有3例在2周内恢复正常,1例有所减轻,但1例在2周后无改善,后经超声心动图检测诊为充血性心力衰竭.初步研究结果提示,大多数患者能够较好地耐受高剂量的CEF化疗方案.