Managing side effects in adjuvant endocrine therapy for breast cancer

Introduction: Recent improvements in the survival of hormone-responsive breast cancer are strongly associated with therapeutic advances, particularly with the uptake of adjuvant endocrine therapy. Nevertheless, endocrine therapy is also linked with adverse effects that impact quality of life, social function, and adherence to treatment.

Areas covered: This review examines the spectrum and consequences of adverse effects of tamoxifen and aromatase inhibitors, and the pharmacological and non-pharmacological approaches to mitigate some of the most frequent and disturbing side effects of endocrine therapy (including vasomotor, musculoskeletal, and vulvovaginal symptoms). The authors performed a qualitative analysis of English papers indexed in PubMed through May 2017, including meta-analysis, randomized controlled trials, observational studies, and systematic reviews.

Expert commentary: Side effects of endocrine treatments are frequent and often underestimated in the care of breast cancer survivors, leading to a poor adherence to treatments that can compromise oncological outcomes. Many of the most common adverse events can be mitigated through pharmacological and non-pharmacological approaches that should be discussed and offered to patients in a dedicated setting of care.     

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。     

The optimal duration of adjuvant endocrine therapy in early luminal breast cancer: A concise review

Patients with luminal early breast cancer are at risk of relapse, even after five years of adjuvant endocrine therapy. To date, no biomarkers have been clinically validated to identify those patients at risk of late recurrence, who might benefit from extended adjuvant endocrine therapy. In recent decades, multiple clinical trials have tested the role of extending adjuvant endocrine therapies in patients with luminal disease. However, the data currently at our disposal are conflicting. This article reviews all the major trials concerning extended adjuvant endocrine regimens, and formulates some general conclusions and hypotheses of future study.     

mTOR表达与雌激素受体阳性乳腺癌辅助内分泌治疗预后的关系

目的探讨雌激素受体（estrogen receptor,ER）阳性乳腺癌中mTOR蛋白的表达与乳腺癌辅助内分泌治疗预后间的关系。方法采用免疫组化方法检测60例ER阳性且接受内分泌辅助治疗患者的原发乳腺癌组织中p-mTOR蛋白的表达情况,观察mTOR蛋白的表达特点.并分析其与临床特征间的关系及对无病生存的影响。结果 mTOR蛋白强阳性表达的乳腺癌细胞具有更多的组织学恶性特征,mTOR阴性组中位无病生存（56.4个月）显著优于阳性组（33.5个月）（P=0.015）,多因素回归分析中mTOR为阳性者发生肿瘤复发转移的风险比例（HR）是mTOR阴性者的3.212倍,其95%CI为1.291～7.992。结论 mTOR表达状态为ER阳性是乳腺癌复发转移的独立预后因素,提示辅助内分泌治疗联合mTOR抑制剂可为ER阳性乳腺癌患者带来生存获益。     

乳腺癌患者应用内分泌药物治疗后合并脂肪肝的临床分析

目的：分析乳腺癌患者应用内分泌药物后发生脂肪肝的机理及预防。方法：收集住院及门诊服用内分泌药物治疗的乳腺癌患者,通过血脂、腹部CT或B超检查,探讨合并脂肪肝的机理。结果：107例患者均有不同程度的脂肪肝发生,轻度脂肪肝42例,中度脂肪肝37例,重度脂肪肝28例。中断内分泌治疗13例。最早发生脂肪肝服药3月,最晚服药近2年,平均13月。结论：乳腺癌服用内分泌治疗的患者应注意预防脂肪肝的发生并给予及早的干预治疗。     

延长辅助内分泌治疗在激素受体阳性早期乳腺癌治疗中的价值

雌激素受体（estrogen receptor,ER）阳性早期乳腺癌的复发风险一直存在。MA.17试验证明,在淋巴结阳性、雌激素受体阳性的乳腺癌患者中,常规应用5年来曲唑治疗后继续应用他莫昔芬治疗,其无病生存期（disease-free survival,DFS）和整体生存期（overall survival,OS）都得到了明显改善。MA.17R试验证明,完成5年芳香化酶抑制剂治疗的患者,继续随机应用来曲唑或安慰剂,来曲唑组的DFS明显改善。在这些研究中,延长内分泌治疗能减少远期复发的绝对益处是适度的,然而其耐受性和依从性的挑战依然存在。对于完成5年常规内分泌治疗的患者,最终是选择他莫昔芬还是来曲唑来延长治疗,主要应该考虑患者的绝经状态、淋巴结情况、耐受性和潜在的利益大小这些因素。     

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。     

乳腺癌内分泌治疗对髓系抑制性细胞的影响

目的分析乳腺癌内分泌治疗药物他莫昔芬和来曲唑对髓系抑制性细胞(MDSC)数量及功能的影响。方法采用简单随机化分组法将53例接受术后辅助治疗的乳腺癌患者随机分为他莫昔芬组(接受他莫昔芬治疗)22例和来曲唑组(接受来曲唑治疗)31例。采用流式细胞术检测两组患者内分泌治疗前及治疗后6个月的外周血MDSC的相对数和绝对数;应用体外培养体系分析并比较两组MDSC对T细胞增殖水平的影响。结果内分泌治疗前,他莫昔芬组与来曲唑组患者的MDSC相对数、绝对数比较,差异均无统计学意义(P﹥0.05);治疗6个月后,来曲唑组患者的MDSC相对数、绝对数分别为(3.09±1.91)%、(1.73±0.35)×106/ml,均明显低于他莫昔芬组的(9.65±3.50)%、(2.92±1.18)×106/ml,差异均有统计学意义(P﹤0.01)。来曲唑组患者的外周血经MDSC处理后CD3+T细胞的增殖水平为(65.93±17.48)%,明显高于他莫昔芬组的(30.25±4.94)%,差异有统计学意义(P﹤0.01)。结论与他莫昔芬比较,乳腺癌患者术后接受来曲唑治疗,可降低MDSC的数量并抑制其功能。     

乳腺癌内分泌治疗新药fulvestrant临床研究进展

Fulvestrant是一种新型雌激素受体(ER)阻滞剂,其降低乳腺癌细胞中ER水平的作用明显优于三苯氧胺(TAM).初步研究表明,在晚期乳腺癌治疗中,fulvestrant与现有的内分泌治疗药物间无交叉耐药,其疗效略优于TAM,至少与阿那曲唑等效且副作用较小,具有较广泛的应用前景.     

乳腺癌化疗致闭经的利弊及随后的内分泌治疗

化疗致闭经是一个客观过程，影响因素基本明确，而且对激素受体阳性的患者，化疗致闭经可改善无病生存和总生存，所以对一些预后好和希望保留卵巢功能的患者我们可以进行干预尽可能保护卵巢功能；而对一些高危、预后差的患者，如果化疗未致闭经，可以采用进一步卵巢抑制的方法，以达到闭经，从而获得更好的疗效，这是一个客观、容易观察的指标。     

Predictors of response to second-line endocrine therapy for breast cancer

This study reports on factors predicting response tosecond-line endocrine therapy in 250 patients with breastcancer for which they were assessable for responseby the International Union Against Cancer (UICC) criteria.Clinical details relating to first-line endocrine therapy wereavailable for all patients. We have not includedin this study patients who received first-line endocrinetherapy but did not or have not yetproceeded to second-line hormone therapy – e.g. diedfrom rapidly progressive disease, started chemotherapy for rapidlyprogressive disease, or remained in long-term remission onfirst-line endocrine therapy.One hundred and fifty nine patients (72%) achievedremission (objective response and static disease [OR +SD]) on first-line endocrine therapy with a medianduration of 19 months. For second-line endocrine therapythe remission rate was 53% (132/225) with amedian duration of 15 months. Tumour grade andoestrogen receptor status of the primary tumour wereshown to be independent predictors of response tosecond-line endocrine therapy while response to first-line endocrinetherapy was a predictor of the duration ofresponse to second-line endocrine therapy. In the sub-groupof patients who showed OR or SD toboth first and second-line therapies, there was nocorrelation between the time to progression (TTP) onfirst and second-line therapies.     

乳腺癌内分泌治疗耐药机制的研究进展

内分泌治疗是雌激素受体阳性乳腺癌的重要系统治疗手段,但原发性与继发性耐药是当前内分泌治疗面临的难题。耐药机制主要包括:ER表达缺失或表观遗传修饰;共调因子表达失衡;雌激素受体通路与生长因子受体（growth factor receptor,GFR）通路的交叉效应;特异性miRNA表达改变;乳腺癌上皮间质转化（EMT）等。根据PubMed检索获取相关资料,就近年来雌激素受体阳性乳腺癌内分泌耐药机制及治疗策略研究进展进行综述。     

乳腺癌新辅助内分泌治疗与靶向治疗联合应用研究进展北大核心

新辅助内分泌治疗是雌激素受体(estrogen receptor,ER)阳性乳腺癌患者的一种潜在的治疗选择,但由于缺乏与新辅助化疗疗效的对比和治疗持续时间的可靠数据,且病理完全缓解率(pathological complete response,pCR)低,目前仅在年老体弱的患者中使用。然而,靶向药物如细胞周期蛋白依赖激酶(Cyclin-dependent kinase,CDK)4/6抑制剂、哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)抑制剂等结合内分泌治疗,已经在晚期乳腺癌的治疗中取得了成功,为患者带来了显著的获益。在早期乳腺癌的新辅助治疗中,内分泌治疗联合靶向治疗仍处于研究阶段,最近的数据展现出了有希望的应用前景。本文旨在评估新辅助内分泌治疗联合靶向治疗在ER阳性乳腺癌治疗中的现状,希望为后续的临床研究及应用提供参考。