来曲唑在老年乳腺癌新辅助内分泌治疗中的疗效观察

目的探讨来曲唑在老年绝经后乳腺癌新辅助内分泌治疗中的近期疗效,耐受性及与临床病理因素的相关性。方法对58例绝经后激素受体阳性的乳腺癌患者进行来曲唑新辅助内分泌治疗,以他莫昔芬新辅助内分泌治疗为对照组。结果来曲唑组临床疗效显著优于他莫昔芬组（P〈0.05）。来曲唑组临床分期晚,ER及PR均阳性的有效率高,与HER-2表达无关。他莫昔芬组HER-2阳性的有效率低。2组治疗前后Ki-67水平均显著下降,有统计学意义（P〈0.05）。2组未出现明显不良反应。结论绝经后、激素受体阳性的乳腺癌选择来曲唑新辅助内分泌治疗安全,有效,尤其适合有合并症的老年体弱者。     

绝经前激素受体阳性乳腺癌辅助内分泌治疗的研究进展

内分泌治疗是激素受体阳性乳腺癌术后辅助治疗的主要手段之一。对于绝经前患者,术后五年的他莫昔芬（TAM）一直是辅助内分泌治疗的金标准,然而,随着诸多旨在提高辅助内分泌治疗疗效研究的发表与更新,辅助内分泌治疗取得较多的进展。本文围绕绝经前乳腺癌阐述当前辅助内分泌治疗的情况,主要分析他莫昔芬（TAM）、芳香化酶抑制剂（AI）、药物性卵巢功能抑制的地位、它们之间联合的优势人群、药物使用的时限等,探讨绝经前早期乳腺癌辅助内分泌治疗的研究进展。     

绝经前乳腺癌患者肿瘤组织中AIB-1蛋白表达与他莫昔芬耐药关系的研究

探讨绝经前乳腺癌患者肿瘤组织中AIB-1蛋白表达与他莫昔芬耐药关系。方法:选取2004年1月至2004年12月河北医科大学第四医院外一科手术切除并经病理证实、且随访资料完整的绝经前女性原发性乳腺癌206例,按照免疫组化检测结果分成:ER+/PR+且接受他莫昔芬治疗组（Tamoxifen group,T组）,ER-PR-的非内分泌治疗组（Contol group,C组）;T组及C组均按AIB-1及Her-2表达状态分为不同亚组。采用Kaplan-Meier法分析各组别无病生存（disease-free survival,DFS）及总生存（overall survival,OS）时间。结果:术后随访30～84个月,中位时间65个月,58例患者出现局部复发或远位转移,5年DFS为71.84%（148/206）;死亡36例,5年OS为82.52%（170/206）。随着组织学分级、腋淋巴结阳性及Her-2蛋白表达的增高,AIB-1蛋白呈现高表达（χ2=12.573,P=0.002;χ2=7.939,P=0.005;χ2=4.502,P=0.036）;分层分析中,T组AIB-1及Her-2均高表达亚组的DFS和OS低于其他亚组,且有统计学差异（χ2=5.900,P=0.002;χ2=4.533,P=0.049）;该亚组患者的生存曲线明显低于其他亚组患者（Log-rank检验,χ2=8.903,P=0.005;χ2=9.405,P=0.004）。结论:AIB-1蛋白高表达常常伴随着不良的临床生物学行为和预后,AIB-1蛋白高表达、同时伴有Her-2高表达的绝经前乳腺癌患者对他莫昔芬治疗耐药,提示AIB-1的表达可以作为预测他莫昔芬耐药的因子。      

乳腺癌的内分泌治疗

内分泌治疗是激素受体阳性的女性乳腺癌患者辅助治疗的重要手段之一,可以降低乳腺癌复发和死亡的风险。近几十年来,他莫昔芬5年疗法已经成为标准治疗。绝经前的妇女也是如此,如果在治疗期间出现绝经,就应该考虑额外使用5年芳香化酶抑制剂(aromatase inhibitors,AIs)。研究表明,绝经后服用AIs预防肿瘤复发方面优于他莫昔芬。该文将使用5年芳香化酶抑制剂、使用2~3年他莫昔芬之后再使用芳香化酶抑制剂、5年他莫昔芬治疗之后继续使用5年芳香化酶抑制剂这三种治疗方案加以比较。     

中国早期乳腺癌卵巢功能抑制临床应用专家共识（2016年版）

乳腺癌已经成为威胁中国女性健康的第一大恶性肿瘤,发病率呈逐年递增趋势。中国乳腺癌发病率年增幅速度是世界平均水平的2倍,且年轻化趋势显著,约有60%的患者在诊断时仍为绝经前状态［1］。据统计,中国绝经前女性早期乳腺癌患者中50%~60%激素受体为阳性,辅助内分泌治疗是降低这类患者复发风险的重要手段,如采用他莫昔芬治疗5~10年已经成为绝经前激素受体阳性的早期乳腺癌患者的标准内分泌治疗方式［2-5］。     

他莫昔芬对乳腺癌患者卵巢的影响

他莫昔芬(tamoxifen,TAM)作为一种非类固醇类抗雌激素药物,自70年代初开始应用于治疗乳腺癌以来,已作为乳腺癌术后辅助治疗和预防复发的主要用药[1]。但长期服用TAM的乳腺癌患者常潜在妇科并发症,我们对我院2000年1月至2004年12月102例服TAM治疗的绝经前后乳腺癌妇女卵巢囊肿发生情况进行分析并探讨对策。1材料和方法1.1研究对象观察组:乳腺癌患者102例,年龄26~75岁,平均年龄59岁。绝经前31例,绝经后71例。对照组:乳腺癌患者46例,年龄32~73岁,平均年龄57岁,绝经前26例,绝经后20例。1.2TAM治疗观察组:口服TAM10mg,一日2次。TAM治疗时…     

他莫昔芬治疗芳香化酶抑制剂耐药的激素受体阳性绝经后转移性乳腺癌患者的临床研究

目的:探讨他莫昔芬治疗芳香化酶抑制剂（AIs）耐药的激素受体阳性（HR+）绝经后转移性乳腺癌（MBC）患者的疗效和安全性。方法:回顾性分析他莫昔芬治疗AIs耐药的30例HR+绝经后MBC患者的临床资料,观察终点为缓解率（RR）、临床获益率（CBR）、疾病进展时间（TTP）和安全性。结果:30例患者中,CR 1例,PR 9例,SD 15例,RR为33.3%,CBR 为50%,中位TTP 6.1个月。23例骨和/或软组织转移患者中,RR为34.8%,CBR为52.2%,中位TTP 7.3个月;7例肝脏和/或肺部转移患者中,RR为28.6%,CBR为42.8%,中位TTP 4.8个月（P=0.019）。不良反应多为面部潮红、阴道干燥、白带增多、阴道出血、恶心、呕吐、腹泻等,均为I、II级。结论:他莫昔芬治疗AIs耐药的HR+绝经后MBC患者安全有效,可改善患者预后。     

绝经前激素受体阳性乳腺癌内分泌治疗现状

内分泌治疗是激素受体阳性乳腺癌患者术后辅助治疗的重要手段之一。在内分泌治疗的背景下,接受5年他莫昔芬治疗一直是绝经前患者的标准治疗方案。近年来,这一标准受到挑战。许多大型随机临床试验结果为绝经前患者辅助内分泌治疗提出了新的选择。本文拟将绝经前激素受体阳性乳腺癌患者的内分泌治疗现状做一综述。     

ER(-)PR(+)乳腺癌辅助内分泌治疗的疗效

背景与目的：孕激素受体（PR）状态是雌激素受体（ER）状态预测乳腺癌辅助内分泌治疗的补充，临床上推荐ER阳性（＋）或PR（＋）患者均可接受内分泌治疗。ER阴性（-）PR（＋）肿瘤应用辅助内分泌治疗的疗效如何还存在争议。本研究将探讨辅助内分泌治疗对ER（＋）PR（＋）与ER（-）PR（＋）乳腺癌的疗效，并研究ER（-）PR（＋）患者的临床病理特性及预后。方法：回顾了1991年1月-2001年12月间的1863位ER／PR资料可用的可手术乳腺癌患者资料，ER、PR均采用免疫组化法检测。中位随访48个月，比较ER（-）PR（＋）组（205例）和ER（＋）PR（＋）组（798例）接受或不接受辅助内分泌治疗（3～5年的他莫昔芬）的无病生存（DFS）和总生存（0s）的差异。结果：ER（-）PR（＋）患者占全部乳腺癌患者的11．0％，中位年龄49岁，肿块中值大小3．0cm，其中未绝经者比例高达63．9％。ER（-）PR（＋）组较ER（＋）PR（＋）组而言，腋淋巴结转移数高、肿块大、分期晚。ER（＋）PR（＋）组和ER（-）PR（＋）组未行内分泌治疗时，组间生存差异无显著性；内分泌治疗后，两组的生存率均有所提高，但ER（＋）PR（＋）组的预后比ER（-）PR（＋）组更好（DFS：P=0．016，OS：P=0．007）。多因素分析显示对ER（-）PR（＋）患者，仅有腋淋巴结状态是独立的预后指标。结论：辅助内分泌治疗对ER（＋）PR（＋）乳腺癌的疗效优于对ER（-）PR（＋）乳腺癌的疗效，ER（-）PR（＋）患者能从内分泌治疗中得到一定收益，但较有限。     

化疗相关性闭经的影响因素分析及对乳腺癌预后的影响

目的:探讨绝经前乳腺癌化疗相关性闭经（chemotherapy-related amenorrhea,CRA）的相关影响因素,并确定患者的5年无病生存率（disease free survival,DFS）和总体生存率（overall survival,OS）,了解化疗后卵巢功能的变化规律及CRA 与预后的关系。方法:回顾性收集于2010年1月至2015年1月就诊于我院确诊为ER+或者PR+216名（≤50岁）新发绝经前乳腺癌患者。收集患者年龄、肿块分期、腋窝淋巴结阳性个数、体质量指数（body mass index,BMI）、病理类型、临床分期、化疗用药方案是否应用他莫昔芬等。采用电话及住院病历查阅等方式随访患者5年,记录患者的闭经、复发、转移和死亡等情况。结果:纳入患者的中位年龄为44.6岁。在接受辅助化疗后,有166例患者出现CRA。其中24名患者恢复月经,142例未恢复月经。CRA的发生与年龄、BMI和他莫昔芬有显著关系（P＜0.05）,而与肿块分期、病理类型、腋窝阳性淋巴结数、临床分期和化疗用药方案等无显著关系（P＞0.05）。此外,我们发现CRA与患者的5年的DFS和OS有显著关系（P＜0.05）,而CRA后恢复月经组与CRA后未恢复月经组患者5年DFS和OS无显著关系（P＞0.05）。结论:辅助化疗能引起绝经前乳腺癌患者卵巢功能的损害,引起女性月经周期的改变,导致闭经。CRA的发生与患者年龄、BMI和他莫昔芬的使用有显著关系。化疗诱导的闭经提示患者有更好的预后。     

来曲唑与三苯氧胺在绝经后期乳腺癌新辅助内分泌治疗中的疗效对比

目的 比较来曲唑与三苯氧胺用于绝经后期乳腺癌新辅助内分泌治疗的近期疗效和毒副反应.方法将收治的绝经后期、ER阳性、有合并症的55例乳腺癌随机分为两组,并行新辅助内分泌治疗.来曲唑组25例:2.5 mg/次,1次/d,连续60 ～90 d;三苯氧胺组30例:10mg/次,2次/d,连续60～90 d.比较两组的近期疗效和...     

Recent perspectives of endocrine therapy for breast cancer

The choice of endocrine therapy for breast cancer depends on the menopausal status and stage of disease. Endocrine therapy remains the first choice and most important component in the treatment of hormone sensitive non-life threatening advanced breast cancer. In premenopausal women with metastatic disease, the combination of a luteinizing hormone-releasing hormone (LH-RH) agonist plus tamoxifen is reasonable as first-line endocrine therapy. In postmenopausal patients with recurrent disease progressing after or during adjuvant tamoxifen, third-generation aromatase inhibitors (AIs) are the preferred first-line endocrine treatment. Many premenopausal and postmenopausal women with hormone responsive breast cancer benefit from sequential use of endocrine therapies at the time of disease progression. Recent clinical trials designs have been implemented, employing AIs as monotherapy in postmenopausal breast cancer patients, as first-line adjuvant therapy, and in sequence either 2-3 or 5 years, with initial tamoxifen. Emerging results from these trials indicate an advantage to patients for any of these strategies, and most international guidelines now suggest the use of an AI in the adjuvant setting in postmenopausal women. The use of endocrine treatment for metastatic and early breast cancer will be reviewed here.     

Contralateral primary tumors in breast cancer patients in a randomized trial of adjuvant tamoxifen therapy

Prophylactic treatment with the anti-estrogen tamoxifen may reduce the risk of breast cancer because estrogens are thought to act as promoters in the pathogenesis of the disease. This article presents results on the incidence of contralateral new primary tumors among 1846 postmenopausal breast cancer patients included in a randomized trial of adjuvant tamoxifen therapy for 2 or 5 years after surgery versus no adjuvant endocrine therapy. The median follow-up was 7 years (range, 3-13 years). There was a significant reduction of contralateral breast cancer in the 931 patients in the tamoxifen group versus that in the 915 control patients (29 versus 47 cases, respectively; P = .03). The cumulative incidence at 10 years in the tamoxifen group and the control group was 5% and 8%, respectively. Analysis of the relative hazard of contralateral tumor over time showed that the benefit with tamoxifen therapy was greatest during the first 1-2 years, but there was a continued risk reduction during the entire follow-up period, i.e., more than 10 years after cessation of treatment. There was no significant difference in the number of contralateral cancers in the patients randomly assigned to 2 or 5 years of treatment, but the 95% confidence interval of the relative hazard was wide. The proportion of estrogen receptor-negative contralateral breast cancers was higher in the tamoxifen group than in the control group. There was no difference, however, between the two groups in recurrence-free survival time from the diagnosis of the contralateral cancer.(ABSTRACT TRUNCATED AT 250 WORDS)     

The role of aromatase inactivators in the treatment of breast cancer

 Third-generation aromatase inhibitors and inactivators have earned their place in the treatment of metastatic breast cancer. The third-generation aromatase inactivator exemestane was found to be superior to megestrol acetate as second-line endocrine therapy in postmenopausal women, with respect to time to progression as well as overall survival, and the results from an ongoing study comparing exemestane with tamoxifen in first-line treatment are promising. The finding that exemestane may also work in patients previously exposed to nonsteroidal aromatase inhibitors reveals lack of complete cross-resistance between the compounds. Currently, exemestane given as monotherapy, or in sequence with tamoxifen (2-3 + 3-2 years of tamoxifen-exemestane or 5 years of tamoxifen followed by 2 years of exemestane) is being compared with tamoxifen 5 years monotherapy in the adjuvant setting. In addition, we are currently addressing the toxicity of exemestane in a placebo-controlled trial in low-risk breast-cancer patients. The results from these studies will outline the potential role of exemestane in adjuvant treatment and, potentially, for breast-cancer prevention in postmenopausal women. Received: April 1, 2002     

Exemestane after tamoxifen as adjuvant hormonal therapy in postmenopausal women with breast cancer: effects on body composition and lipids

Recent studies have shown that administering the aromatase inhibitor exemestane after 2-3 years of tamoxifen therapy significantly improves disease-free survival in postmenopausal women with primary breast cancer in comparison with standard 5-year tamoxifen treatment. Although many of the adverse effects associated with exemestane and tamoxifen have been analysed, there are no comparative data concerning body weight and body composition. The aim of this randomised study was to evaluate the longitudinal changes in body composition and lipid profiles in postmenopausal women switched from tamoxifen to exemestane. In total, 60 overweight or obese postmenopausal patients were enrolled. Their anthropometric data, body composition, including fat mass (FM) and fat-free mass (FFM), and lipid profiles, caloric intake and physical activity were assessed 1 week before randomisation, and 6 and 12 months later. In all, 55 patients (27 on tamoxifen and 28 on exemestane) completed the 1-year study period. Fat mass had significantly decreased by month 12 in the exemestane, but not in the tamoxifen group; the between-group difference was statistically significant (P<0.01). The FFM/FM ratio had significantly increased in the exemestane group, but not the tamoxifen group; the between-group difference was statistically significant (P<0.05). Triglycerides and high-density lipoprotein cholesterol significantly decreased (P<0.01; P<0.05), and low-density lipoprotein cholesterol significantly increased (P<0.01) in the exemestane group at the end of the 1-year study period. Our findings suggest that switching patients to adjuvant exemestane treatment after at least 2 years of tamoxifen therapy may be associated with an advantage over continuing adjuvant tamoxifen treatment in terms of body composition.     

Risk Factors for Tamoxifen-Induced Ovarian Hyperstimulation in Breast Cancer Patients

IntroductionAdjuvant endocrine therapy is an integral component of care for hormone-dependent breast cancer. Tamoxifen is a potent inducer of ovarian function and consequent hyperestrogenism in premenopausal women. However, the incidence rate and risk factors associated this phenomenon remain unclear.Patients and MethodsData of patients younger than 60 years who received adjuvant tamoxifen therapy for hormone-dependent breast cancer (stages 0-III) and who underwent regular follow-up of laboratory results for follicle-stimulating hormone and estradiol levels were retrospectively analyzed. Univariate and multivariate analyses were performed to identify clinicopathologic factors related to ovarian hyperstimulation.ResultsAmong 205 patients, 19 (9.3%) showed high values of serum estradiol during tamoxifen therapy. The mean (± SD) serum concentrations of estradiol and follicle-stimulating hormone were 1047.97 ± 638.8 pg/mL and 11.5 ± 7.3 mIU/mL, respectively. A mean of 400.83 days elapsed from the start of the single administration of tamoxifen to the initial detection of a high concentration of estradiol. Univariate and multivariate analyses showed that younger age (< 40 years) and only endocrine therapy without chemotherapy were significantly related to a higher prevalence of ovarian hyperstimulation (P = .015, relative risk = 7.49 for age < 40 years; P = .017, relative risk = 32.9 for no chemotherapy). Pathologic stages and tumor characteristics were not related to the manifestation of ovarian hyperstimulation.ConclusionYoung age (< 40 years) and endocrine treatment without chemotherapy were risk factors for the incidence of ovarian hyperstimulation during tamoxifen treatment. Close monitoring of endocrine parameters during treatment with tamoxifen especially in this patient group is essential.     

Improved disease-free survival with epirubicin-based chemoendocrine adjuvant therapy compared with tamoxifen alone in one to three node-positive, estrogen-receptor-positive, postmenopausal breast cancer patients: results of French Adjuvant Study Group 02 and 07 trials.

BACKGROUND: The purpose was to compare disease-free survival (DFS) between epirubicin-based chemoendocrine therapy and tamoxifen alone in one to three node-positive (N1-3), estrogen-receptor-positive (ER+), postmenopausal early breast cancer (EBC) patients. PATIENTS AND METHODS: We analyzed, retrospectively, 457 patients randomized in FASG 02 and 07 trials who received: tamoxifen alone (30 mg/day, 3 years); or FEC50 (fluorouracil 500 mg/m2, epirubicin 50 mg/m2, cyclophosphamide 500 mg/m2, six cycles every 21 days) plus tamoxifen started concurrently. Radiotherapy was delivered after the third cycle in FASG 02 trial, and after the sixth in FASG 07 trial. RESULTS: The 9-year DFS rates were 72% with tamoxifen and 84% with FEC50-tamoxifen (P = 0.008). The multivariate analysis showed that pathological tumor size >2 cm was an independent prognostic factor (P = 0.002), and treatment effects remained significantly in favor of chemoendocrine therapy (P = 0.0008). The 9-year overall survival rates were 78% and 86%, respectively (P = 0.11). In the multivariate model, there was a trend in favor of chemoendocrine therapy (P = 0.07). CONCLUSION: The addition of FEC50 adjuvant chemotherapy to tamoxifen significantly improves long-term DFS in N1-3, ER+ and postmenopausal women. Chemoendocrine therapy seems to be more effective than tamoxifen in terms of long-term survival.     

Randomized trial of adjuvant tamoxifen combined with postoperative radiation therapy or adjuvant chemotherapy in postmenopausal breast cancer

From 1976 to 1984, 427 postmenopausal women with high-risk breast cancer (pN + or pT greater than 30 mm) were randomized between postoperative radiation therapy (RT), radiation therapy plus tamoxifen (RT-TAM), adjuvant chemotherapy (CT), or chemotherapy plus tamoxifen (CT-TAM). Surgery was a modified radical mastectomy in all cases. The radiation therapy was given with high-voltage techniques and included the chest wall and regional nodes. The dose was 4600 cGy/4 1/2 weeks. Tamoxifen was given at a dose of 40 mg daily for 2 years. The adjuvant chemotherapy consisted of 12 cycles of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) (or chlorambucil, methotrexate, and 5-fluorouracil [LMF] for patients entered before 1978). At a median follow-up time of 6 1/2 years the recurrence-free survival was significantly better for patients allocated to radiation therapy compared to chemotherapy and for patients allocated to tamoxifen compared to no adjuvant endocrine treatment (P less than 0.01). At 10 years the recurrence-free survival for patients in the RT-TAM, RT, CT-TAM, and CT groups was 63%, 57%, 47%, and 31%, respectively. A significant reduction of treatment failures with tamoxifen was only observed among patients with estrogen receptor-positive tumors. The overall survival difference in favor of patients allocated to radiation therapy or tamoxifen was not significant: the respective survival percentage at 10 years in the RT-TAM, RT, CT-TAM, and CT group was 65%, 62%, 52%, and 50%. The results indicate that postoperative radiation therapy continues to play an important role in the primary management of postmenopausal women with high-risk breast cancer and that the addition of tamoxifen may further improve the results among ER-positive patients.     

Role of adjuvant endocrine therapy in early-stage breast cancer

The value of adjuvant endocrine therapy in saving lives of women with estrogen receptor-positive (ER(+)) early-stage breast cancer cannot be disputed. Tamoxifen has proven to be effective in improving relapse-free and overall survival in both pre- and postmenopausal women with ER(+) early-stage breast cancer. In the meta-analysis of the Early Breast Cancer Trialists' Collaborative Group, the proportional reduction in recurrence and mortality for 5 years of tamoxifen therapy was 50% and 28% respectively for patients with ER(+) tumors. These reductions in recurrence and mortality were similar in both lymph node-negative (N(-)) and lymph node-positive (N(+)) patients and translate to an absolute improvement in 10-year survival of approximately 11% in N(+) patients and 6% in N(-) patients. Current data suggest that about 5 years of tamoxifen therapy is the optimal duration of treatment. For women with ER(-)/progesterone receptor-negative (PR(-)) tumors, tamoxifen does not lower the risk of distant metastases or improve survival. In ER(+) patients, the addition of tamoxifen to chemotherapy further lowers the risk of recurrence by about 30% to 40% when compared to chemotherapy alone. In premenopausal women with ER(+) breast cancer, ovarian ablation has proven to be as effective as chemotherapy in improving both relapse-free and overall survival and the potential additive role of ovarian ablation to chemotherapy and/or tamoxifen is presently being explored in clinical trials. The combination of tamoxifen and ovarian ablation is currently being tested and may be superior to tamoxifen alone. In addition, newer, more effective, and less toxic aromatase inhibitors are also being evaluated in clinical trials in the adjuvant setting and have great promise. "Pure" antiestrogens or selective estrogen receptor down-regulators (SERDs) will be studied in adjuvant clinical trials in the near future. Recent data also suggest that molecular markers such as HER-2/neu may predict the response to endocrine therapy, and other predictive factors are currently being evaluated. Lastly, there is renewed interest in neoadjuvant endocrine therapy, a treatment option that may select those patients with early-stage breast cancer most likely to benefit from endocrine therapy.