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.     

乳腺癌的内分泌疗法

自1896年Beatson首次报道卵巢切除治疗晚期乳腺癌获得成功后,从此,开辟了内分泌治疗恶性肿瘤的新途径.1974年Bethesda召开的国际会议上确认激素受体含量与内分泌治疗疗效之间存在正相关后内分泌治疗乳腺癌的研究更是得到深入的发展.内分泌疗法是乳腺癌治疗的主要手段之一.它不仅用于某些晚期乳腺癌的治疗,也可用于可手术乳腺癌的辅助化疗.但内分泌疗法仅适用于激素依赖性乳腺癌,而不适用于非激素依赖性乳腺癌.ER( )(雌激素受体阳性)者内分泌治疗有效率达50～70%,ER     

乳腺癌新辅助内分泌治疗

随着内分泌治疗药物的发展,新辅助内分泌治疗成为近年来乳腺癌研究的又一热点.大量试验证明,新辅助内分泌治疗能降低肿瘤分期,提高乳腺癌的局部控制率,进一步提高保乳手术率,其中第3代芳香化酶抑制剂的疗效可能优于三苯氧胺.     

乳腺癌辅助内分泌治疗的现状和展望

辅助内分泌治疗是乳腺癌综合治疗中的重要组成部分。19 98年英国早期乳腺癌协作组 (EBCTCG)的资料显示[1],乳腺癌术后用三苯氧胺作为辅助内分泌治疗 ,可使乳腺癌术后复发率相对减少 47% ,死亡率相对减少 2 6%。近年来 ,随着第三代芳香化酶抑制剂逐渐地被用于乳腺癌的辅助内分泌治疗 ,乳腺癌辅助内分泌治疗的疗效有望得到进一步的提高。一、新辅助内分泌治疗乳腺癌新辅助内分泌治疗是指对非转移性乳腺癌在应用局部治疗前进行的系统性内分泌治疗。新辅助内分泌治疗和新辅助化疗相似 ,能够使那些对内分泌治疗敏感的乳腺癌达到原发病灶和区域…     

乳腺癌新辅助内分泌治疗的研究进展

目的:通过文献复习总结目前乳腺癌新辅助内分泌治疗研究的新进展,探讨目前乳腺癌新辅助内分泌治疗研究中的问题及未来发展趋势.方法:应用HighWire、PubMed及CNKI期刊全文数据库检索系统,以"乳腺癌、他莫昔芬、芳香化酶抑制荆和新辅助内分泌治疗"为关键词,检索2000-2010年的相关文献,共检索到英文文献526条.纳入标准:1)乳腺癌的新辅助内分泌治疗.2)他莫昔芬在新辅助内分泌治疗中的应用;3)芳香化酶抑制剂在新辅助内分泌治疗的应用.4)乳腺癌新辅助内分泌治疗综合评价.根据纳入标准,符合分析的文献21篇.结果:乳腺癌新辅助内分泌治疗是最近几年才提出的一种乳腺癌治疗手段,对于雌孕激素受体阳性乳腺癌患者的辅助治疗较化疗有独特的优势.但新辅助内分泌治疗目前尚未成为乳腺癌的常规治疗方法.结论:新辅助内分泌治疗相关的治疗适用对象、治疗药物的选择、用药周期和剂量、疗效评估等多个内容目前仍处于探索阶段.     

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。     

乳腺癌内分泌治疗的现状及研究进展

近年来,随着人民生活水平的提高和生活方式的改变,乳腺癌的发病率呈逐年上升趋势。在我国其发病率也明显上升,已高出世界平均水平1%～2%[1],成为严重威胁我国妇女健康的恶性肿瘤。内分泌治疗在乳腺癌的综合治疗中占有重要地位,可作为术后辅助治疗、术前新辅助治疗及作为复发转移后的补救治疗。因此,了解乳腺癌内分泌治疗的机制,正确把握乳腺癌的治疗策略,掌握最新的内分泌治疗药物,将有助于提高乳腺癌的内分泌治疗效果。一、乳腺癌内分泌治疗的发展过程乳腺癌的内分泌治疗可以追溯到100多年前的1896年,当时Beatson首先报道了3例晚期乳腺癌…     

乳腺癌内分泌治疗的基本共识

内分泌治疗是乳腺癌全身治疗的主要手段之一。20世纪70年代,三苯氧胺的问世成为乳腺癌内分泌药物治疗的里程碑;90年代,第3代芳香化酶抑制剂的问世则使乳腺癌的内分泌治疗进入了一个新时代。2005年1月2日,我国北方部分从事乳腺癌临床工作的专家,根据国内外学术研究进展,结合自身临床实践经验,参考乳腺癌治疗的国际指南,就内分泌治疗在乳腺癌的复发转移、术前新辅助治疗和术后辅助治疗中的作用和地位进行了讨论,并达成基本共识,由执笔者整理成文。     

乳腺癌内分泌治疗的现状与进展

乳腺癌的内分泌治疗,无论是作为乳腺癌术后预防复发转移的辅助治疗,还是复发转移后的解救治疗都有十分重要的地位,与化疗相比,乳腺癌内分泌治疗有其独特的优点:①只要病例选择得当,疗效不比化疗差;②毒副作用较轻、少,有利于巩固治疗;③治疗期间病人的生活质量较高.     

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。     

Systemic therapy of metastatic breast cancer

Recent research has produced several new options for endocrine treatment of metastatic breast cancer. Among these, tamoxifen has become the most commonly used endocrine therapy for metastatic breast cancer due to its few side effects and an overall response rate of 35%. Despite an obvious clinical rationale for combined endocrine therapy, most trials have failed to show any benefit. Although data from trials combining tamoxifen with prednisolone or androgens seem promising, the use of combined endocrine therapy still has to be considered experimental. In patients with metastatic breast cancer, a combination of cytotoxic and endocrine therapy generally leads to a higher rate of remission than in patients treated with either modality alone. The increase in rate of response, however, is not followed by an increase in survival. The combined approach should therefore be explored further in randomized trials, preferably based upon a better understanding of tumor cell kinetics.     

Emerging gene-based prognostic tools in early breast cancer: First steps to personalised medicine

Breast cancer remains a major cause of neoplastic disease in much of the developed world. The majority of cases are diagnosed with oestrogen receptor (ER)-positive and human epidermal growth factor receptor-2 negative invasive ductal carcinoma and are treated predominantly by surgery which includes sentinel node biopsy and adjuvant endocrine therapy ± adjuvant radiotherapy. It is believed that an indeterminate subset of the patient population is needlessly incurring chemotherapy related morbidity without attaining any increase in survival due to therapy. Furthermore in the era of extended adjuvant endocrine therapy it is important to identify those patients who can be safely treated with 5 years rather than 10 years of endocrine therapy thus optimising the benefit-risk balance. This perception has propelled the development of more personalised prognostic tools for newly diagnosed cases of ER-positive breast cancer. In this article, we shall review the evidence regarding the currently available gene assays for human breast cancer.     

Extended Endocrine Therapy: Is 5 Years Enough?

Purpose of Review

Women with hormone receptor (HR)-positive breast cancer remain at risk for cancer recurrence for decades. In this review, we address recent data regarding the benefits and risks of extended endocrine therapy.

Recent Findings

Ten years of treatment with either tamoxifen or an aromatase inhibitor resulted in superior disease-free survival compared to 5 years of treatment. However, there are risks associated with extended therapy with either class of medication. Multiparameter genetic tests are in development to individualize the risk of late breast cancer recurrence and predict benefit from extended endocrine treatment.

Summary

Extended endocrine therapy is a promising strategy to reduce breast cancer recurrence in women with HR-positive breast cancer. This approach should be considered based on individual risk of cancer recurrence compared to potential benefit, comorbidities, and tolerance of therapy.

     

The next era of treatment for hormone receptor-positive,HER2-negative advanced breast cancer: Triplet combination-based endocrine therapies

Until recently, the standard of care for hormone receptor-positive (HR+) breast cancer was single-agent endocrine therapy, which aims to prevent estrogen receptor signaling. This therapeutic strategy has extended survival without the toxicity associated with chemotherapy, but primary endocrine therapy resistance is common, and secondary resistance develops over time. Adjunct downstream inhibition of the cyclin-dependent kinase (CDK)4/6 pathway, intended to delay and prevent endocrine therapy resistance, has further extended progression-free survival in patients receiving endocrine therapy; however, resistance still eventually develops in these patients. Addition of phosphatidylinositol-3 kinase (PI3K) or mammalian target of rapamycin (mTOR) inhibitors to combined CDK4/6 and endocrine inhibitor regimens may help prolong CDK4/6 inhibitor sensitivity. Early trials combining CDK4/6 inhibitors, PI3K or mTOR inhibitors, and endocrine therapy have shown encouraging signs of clinical activity. However, further research is needed to help understand the extent of treatment benefit from triplet therapy and where this strategy will fit in the treatment sequence for patients with HR+ breast cancer.     

Exemestane: a potent irreversible aromatase inactivator and a promising advance in breast cancer treatment

With the introduction of orally-active, potent and selective third-generation aromatase inhibitors and inactivators – anastrozole, letrozole and exemestane – approaches to the treatment of advanced breast cancer are undergoing re-evaluation. In advanced breast cancer, aromatase inhibitors and inactivators are likely to become established as the primary choice over tamoxifen in postmenopausal female breast cancer patients when hormonal therapy is indicated in the first-line setting. The current evaluation of exemestane, an oral steroidal irreversible aromatase inactivator, for primary and adjuvant therapy and the potential role of potent estrogen-deprivation therapy in prevention of postmenopausal breast cancer may extend the use of antiaromatase therapy as an increasingly valuable palliative treatment option, conferring survival benefit and possible preventive outcomes across several treatment settings in the management of breast cancer.     

Neoadjuvant endocrine treatment of women with breast cancer

Neoadjuvant therapy has four goals in breast cancer: decrease tumor volume to operate tumors that initially were inoperable, increase the number of conservative surgeries, evaluate the chemosensitivity in vivo and analyze the management of micrometastases. Neoadjuvant treatment provides a unique setting in which we can monitor clinical, pathological, proliferative and molecular responses. Combining different strategies such us surgery, radiation therapy, chemotherapy, and endocrine therapy has contributed substantially to the survival improvement in breast cancer. Third-generation aromatase inhibitors have proven to be superior to tamoxifen in the adjuvant and, more recently, the neoadjuvant treatment of postmenopausal patients. The need to define how to select the patients that will benefit the most from these therapies, the optimal duration of treatment, the best method to evaluate the treatment response, the identification of predictive factors for response, and the superiority of certain endocrine agents over others have been reviewed. We have carried out a critical analysis of the current literature on the utilization of endocrine therapy in the neoadjuvant setting for breast cancer. This review discusses the current evidence regarding primary endocrine therapy and the current opinions on length of treatment and measurement of response prior to surgery.     

The use of endocrine therapy

Endocrine therapy is still a mainstay in the treatment of metastatic breast cancer. It has been observed that about one third of women with metastatic breast cancer will respond to endocrine therapy. This response rate is surprisingly consistent for a wide variety of endocrine approaches, with a few exceptions, such as the use of corticosteroids, androgens, or danazol for which the response rate appears lower. Endocrine therapy is, in general, considerably less toxic than single or combination chemotherapy, but toxicities within the endocrine therapies may vary considerably. Thus, the choice and optimal sequencing of endocrine maneuvers relate largely to minimizing toxicity and optimizing total duration of benefit. A number of newer endocrine approaches including the antiestrogens and aminoglutethimide have recently provided a variety of less toxic choices. Even more recently, compounds such as the LHRH agonists and antiandrogens are being tested, although their use remains experimental. Combinations of two or more endocrine therapies or of chemotherapy and endocrine therapy are currently, also a subject of considerable interest. No studies to date, however, have shown a clear advantage to concurrent chemotherapy endocrine combinations or to the use of two or more concurrent hormonal maneuvers, with the possible exception of the combination of prednisolone with tamoxifen or with oophorectomy, which has improved overall survival in two trials.     

Exclusive endocrine therapy or partial breast irradiation for women aged ≥70 years with luminal A-like early stage breast cancer (NCT04134598 – EUROPA): Proof of concept of a randomized controlled trial comparing health related quality of life by patient reported outcome measures

BackgroundPostoperative radiation therapy after breast conserving surgery in the older adult population is a matter of debate; although radiation therapy was shown to benefit these patients concerning local disease control, the absolute benefit was small and potentially negligible. Partial breast irradiation has been introduced as an alternative treatment approach for low-risk patients. Older adult patients with early breast cancer constitute a unique population with regards to prognosis and potential comorbidities, thus minimizing treatment to maintain health-related quality of life (HRQoL) without compromising survival is extremely important. Estimates of the patient's risk of benefit and/or harm with treatment should be performed together with an assessment of baseline comorbidities, life expectancy, and care preferences. Published data suggest that radiation therapy or endocrine therapy alone resulted in excellent disease control in older women with early breast cancer, and that the combination of both treatments has less incremental benefit than expected. Conversely, the toxicity profile of endocrine therapy is well known, often significantly impacting long term HRQoL of these potentially frail patients.MethodsPatients older than 70 years receiving breast conserving surgery with T1N0, Luminal A-like tumors will be randomized to receive partial breast irradiation-alone or endocrine therapy-alone. The main objectives are to determine patient reported outcome measures in terms of HRQoL, as assessed by the EORTC QLQ-C30 using the global health status of patients, and to demonstrate a non-inferior local control rate between arms. Secondary endpoints are represented by individual scales from QLQ-C30 and module QLQ-BR45 scores; ELD14 questionnaire; geriatric COre DatasEt assessment; distant control rate, adverse events rates, breast cancer specific, and overall survival.DiscussionThe EUROPA trial is a new randomized trial focused on older adults (≥70 years) affected by good prognosis primary breast cancer. Our assumption is that postoperative radiation therapy-alone avoids the long-term toxicity of endocrine therapy and favorably impacts on HRQoL in this population. In the current report we present the trial's background and methods, focusing on perspectives in the field of precision medicine.Trial registration: The trial is registered with ClinicalTrial.gov Identifier NCT04134598 / EUROPA trial.     

Current status of adjuvant chemotherapy for breast cancer

Breast cancer is one of the most common malignancies among Japanese women. Approximately 40,000 new patients are diagnosed annually. In the USA, however,the mortality from breast cancer has recently been declining. A nationwide screening promotion using mammography, and recent advances in the treatment for early breast cancer have been the main reasons. It was widely accepted that for breast cancer as a systemic disease, appropriate systemic treatment of either chemotherapy and endocrine therapy improved the survival. We describe here the contributions of new agents to the improvement in survival for breast cancer patients and introduced the concept of dose density.     

Controversies in the therapy of early stage breast cancer

Breast cancer is the most common malignancy among U.S. women, with more than 200,000 new cases diagnosed annually. In the U.S., mortality from breast cancer has declined in recent years as a result of more widespread screening, leading to earlier detection, as well as advances in the adjuvant treatment of early-stage disease. It is widely accepted that the appropriate use of adjuvant chemotherapy and endocrine therapy improves the disease-free and overall survival of patients with early-stage breast cancer. It is, therefore, standard clinical practice to administer adjuvant systemic therapy to patients with node-positive and high-risk, node-negative breast cancer. There remain, however, many controversies in the primary systemic therapy of breast cancer, which are discussed in this review.