激素受体阳性/人表皮生长因子受体2阳性晚期乳腺癌的多靶向治疗研究进展

在乳腺癌患者中,约20％的患者存在肿瘤细胞人表皮生长因子受体2(HER2)过表达,使得肿瘤侵袭性更强,预后更差.针对这一特点,有靶向治疗方案以控制疾病进展.进一步研究发现,有将近50％的HER2阳性乳腺癌患者同时表达激素受体(HR),HER2与HR在下游通路存在交互作用,而这一特性也与乳腺癌患者的内分泌耐药及抗HER2治疗耐药相关.临床试验证实,针对HR+/HER2+这一亚组,靶向治疗联合内分泌治疗可为患者带来更大的生存获益,目前化疗仍然为该亚组患者的首选治疗方案.本文总结了针对HR+/HER2+晚期乳腺癌治疗的相关文献,探讨靶向治疗联合内分泌治疗是否可作为该亚组治疗的另一优选方案.     

激素受体阳性早期乳腺癌治疗现状与挑战

在早期发现、有效治疗的情况下,早期乳腺癌是可治愈的,长期无病生存应是早期患者所追求的治疗目标.既往认为乳腺癌各亚型中激素受体(hormone receptor,HR)阳性早期乳腺癌预后最好,然而随着人类表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)阳性乳...     

延长内分泌治疗在激素受体阳性早期乳腺癌治疗中的获益分析

目的 探讨延长辅助内分泌治疗能否改善激素受体阳性早期乳腺癌患者的预后,为临床治疗方案提供参考依据.方法 检索PubMed、ASCO会议和圣安东尼奥会议报告,以及相关中文数据库中2018-08-31前发表的临床研究及报告.应用RevMan 5.3软件行Meta分析.结果 共纳入随机对照试验文献13篇,共计32 280例患...     

晚期雌激素受体阳性乳腺癌的治疗进展

针对晚期雌激素受体阳性乳腺癌虽然主要使用内分泌、靶向等治疗方法,但内分泌治疗的耐药问题在临床上较常见。随着对CDK4/6、PI3K-Akt1-mTOR通路等治疗靶点和耐药机制的研究,晚期雌激素受体阳性乳腺癌的靶向治疗已成为研究热点,利用基因靶向治疗等也可能成为新的突破点,同时在如何针对不同患者选择最佳治疗方案、最佳治疗时间等问题上仍存在挑战。本文将就晚期雌激素受体阳性乳腺癌的治疗进展进行综述。      

乳腺癌内分泌治疗中激素受体问题

雌激素受体(ｅｓｔｒｏｇｅｎｒｅｃｅｐｔｏｒ,ＥＲ)已被作为乳腺癌内分泌治疗和预后评估的一个重要指征。近年来的研究已取得显著进展,特别是有关实际应用中存在的一些问题,许多已有较明确的解释。现就一些有关新认识、新进展做一概要综述。一、雌激素、激素受体与乳腺癌1896年Ｂｅｎｔｓｏｎ发现乳腺细胞的增生及癌变与激素密切相关,并观察到切除卵巢可使进展期乳腺癌消退。1967年Ｊｅｎｓｅｎ发现人类乳腺癌中含有ＥＲ。这一发现把乳腺癌内分泌治疗推向了崭新的阶段,使内分泌治疗变得有的放矢,疗效明显提高。研究证明,有的肿瘤细胞恶变…     

哌柏西利联合内分泌治疗晚期激素受体阳性乳腺癌的真实世界研究

目的评价哌柏西利联合内分泌治疗HR+/HER2−晚期乳腺癌患者的疗效及安全性。方法回顾性分析2018年9月15日至2020年10月30日本中心83例采用哌柏西利联合内分泌治疗的HR+/HER2−晚期乳腺癌患者的临床资料,评估其临床疗效、无进展生存期(PFS)及不良反应。结果共纳入的83例HR+/HER2-晚期乳腺癌患者,中位随访时间为15.5个月,一线(n=25)和二线(n=38)采用哌柏西利联合内分泌治疗患者的ORR高于多线治疗患者(n=20),但差异无统计学意义(48.0%vs 44.7%vs 30.0%,P=0.466),3组患者的疾病控制率差异也无统计学意义(96.0%vs 89.5%vs 80.0%,P=0.337)。哌柏西利联合组全人群mPFS为13.0个月(95%CI:11.4~14.6个月),一线/二线治疗患者的mPFS较多线治疗患者延长(20.0个月vs 14.0个月vs 5.0个月,P<0.001),仅有骨转移的患者mPFS优于非骨转移患者(未达到vs 13.0个月;HR=0.42,95%CI:0.22~0.84,P=0.01);无内脏转移患者的mPFS优于存在内脏转移患者,但差异无统计学意义(20.0个月vs 13.0个月;HR=0.65,95%CI:0.35~1.22,P=0.38)。依维莫司联合内分泌治疗耐药患者应用哌柏西利治疗仍可获益(mPFS=5个月)。83例患者采用哌柏西利联合治疗后常见和严重的不良反应均为中性粒细胞减少,其中12例因不良反应下调剂量。结论哌柏西利联合内分泌治疗HR+/HER2-晚期乳腺癌患者的临床疗效显著,尤其是一/二线治疗取得较好疗效,安全性良好。     

三阳性乳腺癌内分泌治疗联合靶向治疗的研究进展

三阳性乳腺癌(triple-positive breast cancer,TPBC)是指雌激素受体、孕激素受体和人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)表达均为阳性的乳腺癌,占所有乳腺癌病理学类型的5%～10%。TPBC是Luminal B型乳腺癌亚型的一种特殊类型,既可以接受内分泌治疗,又可以接受靶向治疗。目前国内外指南推荐TPBC的治疗首选抗HER2靶向治疗联合化疗,但TPBC新辅助治疗的病理学完全缓解率却低于激素受体阴性/HER2阳性乳腺癌,且雌激素受体表达>30%的患者从抗HER2靶向治疗联合化疗中获益较小。目前随着多种抗HER2靶向药物不断问世,以及细胞周期蛋白依赖性激酶4和6抑制剂的临床应用,使得临床上对于高选择的患者首选靶向治疗联合内分泌治疗成为可能。本文就TPBC内分泌治疗联合靶向治疗的最新研究进展进行综述。     

CDK4/6抑制剂在激素受体阳性进展期乳腺癌治疗中的研究进展

内分泌治疗因其兼具良好的疗效及安全性,是激素受体阳性进展期乳腺癌患者的重要治疗手段。近年来内分泌领域进展迅速,很多新型药物相继出现,其中包括多种可以逆转或延迟内分泌耐药的周期蛋白依赖性激酶(cyclin-dependent kinase,CDK)4/6抑制剂。CDK4/6抑制剂联合内分泌治疗可为激素受体阳性进展期乳腺癌患者带来生存获益、延迟至化疗时间,正逐渐改变国内外激素受体阳性进展期乳腺癌的治疗模式。本文将就CDK4/6抑制剂在激素受体阳性进展期乳腺癌中的治疗进展进行综述。     

激素受体阳性乳腺癌脑转移药物治疗研究进展

目的 乳腺癌是仅次于肺癌最易发生脑转移的原发肿瘤.激素受体阳性乳腺癌是转移性乳腺癌的主体,脑转移是该类患者的主要死亡原因,但目前对于激素受体阳性乳腺癌脑转移(breast cancer brain metastases,BCBM)的有效治疗报道较少.本研究旨探讨激素受体阳性BCBM药物治疗的相关研究进展.方法 应用PubMed及CNKI期刊全文数据库检索系统,以"乳腺癌、脑转移和激素受体阳性乳腺癌"等为,检索2005-01-2016-06相关文献,共检测到中文文献128条,英文文献55条.纳入标准:1)BCBM的危险因素及其预后;2)BCBM的当前治疗选择;3)激素受体阳性BCBM药物治疗.根据纳入标准,符合分析的文献25篇.结果限制BCBM药物治疗进展的主要原因是血脑屏障的存在.激素在BCBM治疗中的疗效尚不明确,但有大量个案报道他莫昔芬等内分泌药物对BCBM治疗有效.非对照试验表明某些细胞毒类药物,如卡培他滨、替莫唑胺(temozolomide,TMZ)和卡莫司汀晶片植入剂,对激素受体阳性BCBM有效,但没有足够证据支持具体的治疗方案.免疫抑制剂abemaciclib在激素受体阳性BCBM患者中的应用正处于Ⅱ期临床试验阶段.虽然高分子药物难以通过完整的血脑屏障,但研究证实部分单克隆抗体,如曲妥珠单抗和贝伐单抗,对BCBM治疗有效.纳米药物传递系统能提高中枢神经系统药物转移,有较好发展前景.由纳米颗粒包裹的多柔比星和etirinotecanpegol对治疗激素受体阳性BCBM有一定的疗效.结论尽管目前没有专门批准用于激素受体阳性BCBM系统治疗的药物,但有大量的临床试验正在进行中,将为临床治疗带来启示.     

激素受体阳性晚期乳腺癌的内分泌治疗进展

内分泌耐药是激素受体阳性晚期乳腺癌的治疗难题之一.根据耐药机制,内分泌治疗引入靶向药物有望逆转或延迟耐药,并已在临床研究中取得验证.寻找分子标志物,选择获益人群,是这个领域发展的重要方向.     

乳腺癌分子靶向治疗与生物化疗

乳腺癌的治疗,继手术、放疗和化疗三大传统模式之后,生物治疗已被公认为治疗恶性肿瘤的第四大模式;分子靶向治疗药物的出现和在临床的广泛应用,使得生物治疗在肿瘤的综合治疗中发挥了日渐重要的作用.生物治疗与化疗的结合,提出了恶性肿瘤的治疗的新概念-生物化疗的概念.     

Drug withdrawal in women with progressive metastatic breast cancer while on aromatase inhibitor therapy

Background:

Acquiring resistance to endocrine therapy is common in metastatic hormone-receptor-positive breast cancer (MBC). These patients most often transition either to next-line endocrine therapy or to systemic chemotherapy. However, withdrawal of endocrine therapy and observation as is selectively practiced in prostate cancer is another potential strategy for breast cancer patients.

Methods:

A prospective, single-arm phase II trial of aromatase inhibitor (AI) withdrawal was performed in women with MBC, who had disease progression on AI therapy. The primary objective was to estimate the clinical benefit rate (defined as complete or partial response, or stable disease for at least 24 weeks, by RECIST criteria). Participants were monitored clinically and radiographically off all therapy at 8, 16 and 24 weeks after treatment and every 12 weeks thereafter until disease progression.

Results:

Twenty-four patients (of 40 intended) were enrolled when the study was closed due to slow accrual. Clinical benefit rate overall was 46% (95% CI 26% to 67%). Median progression-free survival from time of AI withdrawal was 4 months. Two patients have remained progression free, off all treatment, for over 60 months.

Conclusions:

Despite suboptimal patient accrual, our results suggest that selected patients with metastatic breast cancer progressing on AI therapy can experience disease stabilisation and a period of observation after AI withdrawal. A randomised phase II trial is planned.     

An overview of menopausal oestrogen-progestin hormone therapy and breast cancer risk

Results from the Women's Health Initiative (WHI) trial support findings from observational studies that oestrogen-progestin therapy (EPT) use is associated with an increase in breast cancer risk. We conducted a meta-analysis using EPT-specific results from the Collaborative Group on Hormonal Factors in Breast Cancer (CGHFBC) pooled analysis and studies published since that report to obtain an overview of EPT use and breast cancer risk. We also assessed risk by histologic subtype of breast cancer, by schedule of the progestin component of EPT, and by recency of use. We estimate that overall, EPT results in a 7.6% increase in breast cancer risk per year of use. The risk was statistically significantly lower in US studies than in European studies - 5.2 vs 7.9%. There was a significantly higher risk for continuous-combined than for sequential EPT use in Scandinavian studies where much higher total doses of progestin were used in continuous-combined than in sequential EPT. We observed no overall difference in risk for lobular vs ductal carcinoma but did observe a slightly higher risk for current vs past EPT use.     

2016年美国ASCO年会乳腺癌内分泌治疗进展

内分泌治疗是乳腺癌治疗的主要手段之一,近年来,辅助内分泌治疗强化或延长治疗策略、内分泌治疗新型药物以及围绕内分泌治疗耐药的液态检测都是临床研究关注的热点,现将2016年美国ASCO会议内分泌治疗的进展进行综述.     

Estrogen and progesterone receptors: Correlation of response rates,site and timing of receptor analysis

Summary 156 patients with advanced breast cancer of known estrogen receptor (ER) and progesterone receptor (PgR) status treated by endocrine therapy were studied. Regarding values for ER and PgR 5 fmole/mg cytosol protein as positive, patients were divided into 4 phenotypic subgroups: ER⁺PgR⁺ (43%), ER⁺PgR^– (26%), ER^–PgR⁺ (8%), and ER^–PgR^– (23%). In patients with tumor phenotype ER⁺PgR⁺, responses were seen in 20/30 (67%) assessable initial treatments when receptor assays were performed on tumor recurrence or on primary tumor immediately before endocrine therapy, and in only 11/32 (34%) assessable initial treatments when receptor analysis was performed on primary tumor and there was intervening local therapy before endocrine therapy was started for tumor recurrence (P<0.05).Responses to first endocrine therapy for each tumor phenotype were ER⁺PgR⁺ 50%, ER⁺PgR^– 27%, ER^–PgR⁺ 27%, and ER^–PgR^– 6%. Four of 16 (25%) patients with ER⁺PgR⁺ tumors responded to subsequent secondary endocrine therapy, but such responses were not observed in 20 patients with other tumor phenotypes.Duration of response was similar for each phenotype, but patients with ER^–PgR^– tumors had a significantly shorter survival from time of initial endocrine treatment than patients of any other phenotype.These results suggest that repeat steroid receptor assays on accessible tumor immediately before endocrine therapy may result in improved predictability. Address for reprints: Dr R.D. Rubens, Imperial Cancer Research Fund, Breast Cancer Unit, Guy's Hospital, London SE1 9RT, United Kingdom.     

晚期三阴乳腺癌挽救治疗进展

三阴乳腺癌约占全部乳腺癌病例的15％,具有恶性程度高,进展快,生存期短和预后较差的临床特点.因此近些年来,三阴乳腺癌受到越来越多的国际肿瘤学界的关注.化疗是晚期三阴乳腺癌治疗的核心,但目前没有统一标准的化疗方案.另外,靶向治疗是晚期三阴乳腺癌一个较有前途的治疗新策略.现对晚期三阴乳腺癌的挽救治疗做一综述.