ASCO最新指南提倡讨论乳腺癌化学预防

根据《临床肿瘤学杂志》7月8日在线发表的美国临床肿瘤学会(ASCO)最新临床实践指南，医生应与年龄≥35岁的乳腺癌风险增高的女性讨论使用他莫昔芬预防该病。此外，应与乳腺癌风险增高的绝经后女性讨论使用选择性雌激素受体调节剂——雷洛昔芬和依西美坦(J. Clin. Oncol. 2013 July 8 [doi 10.1200/JCO.2013.49.3122])。

此次更新的内容是由更新委员会联合主席Kala Visvanathan博士及其他委员会成员通过系统评价2007年6月~2012年6月间发表的700多项潜在随机对照试验和meta分析编写。最终，共有19篇探讨6种不同化学预防药物的论文符合委员会的选择标准。

最新指南的建议仅限于药物干预，提倡与患者讨论以下药物方案：

·对于年龄≥35岁的乳腺癌风险增高或患有小叶原位癌(LCIS)的绝经前和绝经后女性，为了降低雌激素受体(ER)阳性浸润性乳腺癌的风险，建议每日口服他莫昔芬20 mg治疗5年。风险增高定义为根据美国国立癌症研究所乳腺癌风险评估工具或等效工具预测的5年绝对风险≥1.66%。这一“强烈循证建议”基于多项随机对照试验的观察结果，即口服他莫昔芬治疗降低风险的获益在这些患者中可持续至少10年。

·对于年龄≥35岁的乳腺癌风险增高或患有LCIS的绝经后女性，为了降低ER阳性浸润性乳腺癌的风险，建议每日口服雷洛昔芬60 mg治疗5年。这一“强烈循证建议”也基于多项随机对照试验的观察结果。

·对于年龄≥35岁的乳腺癌风险增高或患有LCIS的绝经后女性，为了降低ER阳性浸润性乳腺癌的风险，建议每日口服依西美坦25 mg(代替他莫昔芬或雷洛昔芬)治疗5年。这一“中度循证建议”基于一项有关该芳香化酶抑制剂的随机对照试验的阳性结果。目前该药已被批准用于治疗乳腺癌但尚未获准用于预防乳腺癌。

不建议有深静脉血栓形成、肺栓塞、卒中或短暂性脑缺血发作史的女性使用他莫昔芬和雷洛昔芬，另外也不建议在长期制动期间使用这两种药物。不建议妊娠或可能妊娠或正在哺乳的女性使用他莫昔芬，并且该药不得与激素治疗联用。依西美坦不得用于绝经前女性。

委员会表示，与患者讨论的内容应包括所考虑使用的各种药物的风险和获益。

除了上述有关讨论使用他莫昔芬和雷洛昔芬方面的变更之外，最新指南还删除了2009年版指南中“在开始治疗前进行基线妇科检查并且此后每年检查1次”的建议；同时最新指南还删除了有关芬维A胺治疗的内容，因为委员会确定其“与乳腺癌化学预防不再具有相关性”。

指南指出，一般而言，少数族裔患者往往在较晚期才被诊断出癌症且结局不良。应认识到治疗质量和治疗可及性方面存在的这些差异。医生应努力为所有患者提供最高水平的癌症治疗。委员会表示，目前乳腺癌化学预防药物在乳腺癌风险增高女性中的应用率较低，未来需解决与此相关的诸多问题。约有至少2百万女性可从乳腺癌化学预防中获益，但本指南推荐的药物仍然较少被用于降低乳腺癌风险。需设计有效的工具和方法来教育医生及识别风险增高的女性，并且需开发有效的干预及更深入地了解在应用化学预防策略方面存在的差异和障碍。

Visvanathan博士表示，并非所有女性都应当使用这些预防药物，但应该为乳腺癌风险增高的女性提供药物选择，因为这些治疗可使部分女性的乳腺癌风险明显降低，降幅可达50%。

访问ASCO网站，可获取补充性的相关图表及临床工具和资源，帮助临床医生实施本指南。

Visvanathan博士声明无经济利益冲突。其他委员会成员声明与诺华等多家公司存在利益联系。

爱思唯尔版权所有  未经授权请勿转载

By: SHARON WORCESTER, Internal Medicine News Digital Network

Tamoxifen for the prevention of breast cancer should be discussed with women aged 35 years or older who are at increased risk for the disease, according to an updated clinical practice guideline from the American Society of Clinical Oncology.

The use of raloxifene and exemestane should be discussed with postmenopausal women who are at increased risk for the disease, according to the update – the third since the guideline, entitled "Use of Pharmacologic Interventions for Breast Cancer Risk Reduction," was first published in 1999, and the first since 2009 (J. Clin. Onco. 2009;27:3235-58).

The new update includes stronger wording regarding discussion about the selective estrogen-receptor modulators tamoxifen and raloxifene, compared with the 2009 version, which stated that tamoxifen and raloxifene "may be offered" to women at increased risk.

"The committee felt that a stronger statement recommending the use of tamoxifen and raloxifene was needed given the weight of evidence from phase III randomized trials demonstrating a reduction in breast cancer risk for both tamoxifen and raloxifene," Update Committee cochair, Dr. Kala Visvanathan of Johns Hopkins Medical Institutions, Baltimore, and the other committee members reported (J. Clin. Oncol. 2013 July 8 [doi 10.1200/JCO.2013.49.3122]).

The guideline recommendations, which were published online on July 8 in the Journal of Clinical Oncology, and which are limited to pharmacologic interventions, specifically call for discussing with patients the options of:

·Oral tamoxifen treatment at a dose of 20 mg daily for 5 years to reduce the risk of estrogen receptor- (ER) positive invasive breast cancer in both pre- and postmenopausal women aged at least 35 years who are at increased risk of breast cancer or who have lobular carcinoma in situ (LCIS). Increased risk is defined as a 5-year projected absolute risk of 1.66% or greater according to the National Cancer Institute Breast Cancer Risk Assessment Tool or an equivalent measure. This "strong, evidence-based recommendation" is based on data from multiple randomized, controlled trials showing that the risk reduction benefit of this treatment continues for at least 10 years in these patients.

·Oral raloxifene treatment at a dose of 60 mg daily for 5 years to reduce the risk of ER-positive invasive breast cancer in postmenopausal women aged at least 35 years who are at increased risk or who have LCIS. This "strong, evidence-based recommendation" also is based on data from multiple randomized, controlled trials.

·Oral exemestane at a dose of 25 mg daily for 5 years as an alternative to tamoxifen or raloxifene to reduce the risk of ER-positive invasive breast cancer in postmenopausal women aged at least 35 years who are at increased risk of breast cancer or who have LCIS. This "moderate, evidence-based recommendation" is based on encouraging evidence from a single randomized, controlled trial of the aromatase inhibitor, which is approved for the treatment of breast cancer but not for breast cancer prevention.

Tamoxifen and raloxifene are not recommended for use in women with a history of deep vein thrombosis, pulmonary embolus, stroke, or transient ischemic attack, nor are they recommended during prolonged immobilization. Tamoxifen is not recommended in women who are pregnant or who may become pregnant or in women who are nursing, and it should not be used in combination with hormone therapy. Exemestane should not be used in premenopausal women, according to the guideline.

"Discussions with patient and health care providers should include both the risks and benefits of each agent under consideration," the committee said.

The guideline update is based on a systematic review of more than 700 potential randomized controlled trials and meta-analyses published between June 2007 and June 2012. Ultimately, 19 articles on six different chemoprevention agents met the selection criteria of the committee, which was convened by the ASCO Clinical Practice Guidelines Committee. Members were experts – with special expertise in breast cancer – from clinical medicine, public health, clinical research, health services, and related areas such as biostatistics and epidemiology. A patient representative also was appointed to the committee.

In addition to the changes regarding the discussion of tamoxifen and raloxifene, the updated guideline also eliminates a recommendation from the 2009 version calling for a baseline gynecologic examination before initiation of treatment and annually thereafter, and removes mention of treatment with fenretinide, which the committee determined is "no longer relevant for breast cancer chemoprevention."

The committee also addressed ongoing challenges with respect to minimizing health disparities, which the committee said "are an important consideration in reducing breast cancer risk."

"Members of racial and ethnic minorities, in general, tend to be diagnosed with cancer at more advanced stages and have worse outcomes ... Awareness of these disparities in quality of care and access to care should be considered in the context of this clinical practice guideline. Health care providers should strive to deliver the highest level of cancer care to all patients," the guideline states.

As for future directions, the committee stressed a need for addressing "the many unresolved issues related to the poor uptake of breast cancer chemoprevention agents in women who are at increased risk of breast cancer."

An estimated 2 million or more women could benefit from breast cancer chemoprevention, yet the agents recommended in this guideline are used infrequently for breast cancer risk reduction, the committee said, noting a need for the design of effective tools and approaches to educate providers and identify women at increased risk, and for efficacious interventions and greater understanding of the disparities and barriers that exist regarding use of chemoprevention strategies.

"Not every woman should use these preventive agents, but we believe women who are at increased risk for breast cancer should be given the option, because in some cases the magnitude of the risk reduction is large. For some women, these therapies can reduce the risk of breast cancer by up to 50%," Dr. Visvanathan said in a press statement.

A data supplement with tables and figures, and clinical tools and resources to help clinicians implement this guideline is available at ASCO’s website.

Dr. Visvanathan reported having no disclosures. Other Update Committee members reported serving as consultants and/or receiving honoraria or research funding from Novartis, Pfizer, Bayer, Champions Biotechnology, and/or AstraZeneca. One author also reported owning Novartis stock.